Anti psori recenzii nano psoriazis Anti psori recenzii nano psoriazis


Anti psori recenzii nano psoriazis

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Sum of PLOS and PubMed Central page views and downloads. Sum of Facebook and Twitter activity. Affiliation Center for Clinical and Translational Science, Rockefeller University, New York, New York, United States of America. Yao Y, Richman L, Morehouse C, de los Reyes M, Higgs BW, et al. Potential Therapeutic Target for Psoriasis?. PLOS ONE 4 3: Psoriasis is an immune-mediated disease characterized by aberrant epidermal differentiation, surface scale formation, and marked cutaneous inflammation.

To better understand the pathogenesis of this disease and identify potential mediators, we used whole genome array analysis to profile paired lesional and nonlesional psoriatic skin and skin from healthy donors. We observed robust overexpression of type I interferon IFN —inducible genes and genomic signatures that indicate T cell and dendritic cell infiltration in lesional skin. Up-regulation of mRNAs anti psori recenzii nano psoriazis IFN-α subtypes was observed in lesional skin compared with nonlesional skin.

Enrichment of mature dendritic cells and 2 type I IFN—inducible proteins, STAT1 and ISG15, were observed in the majority of lesional skin biopsies. Concordant overexpression of IFN-γ and TNF-α—inducible gene signatures occurred at the same disease sites. Up-regulation of TNF-α and elevation of the TNF-α—inducible gene signature in lesional skin underscore the importance of this cytokine in psoriasis; these data describe a molecular basis for the therapeutic activity of anti—TNF-α agents.

Furthermore, these findings implicate type I IFNs in the pathogenesis of psoriasis. Consistent and significant up-regulation of type I IFNs and their associated gene signatures in psoriatic skin suggest that type I IFNs may be potential therapeutic targets in psoriasis treatment.

Yao Y, Richman L, Morehouse C, de los Reyes M, Higgs BW, Boutrin A, et al. Potential Therapeutic Target for Psoriasis? PLoS ONE 3 7: March 11, ; Accepted: June 24, ; Published: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the anti psori recenzii nano psoriazis author and source are credited.

All authors but one are employees of MedImmune. There were no additional sponsors or funders. The authors have declared that no competing interests exist. Although originally viewed as a disease primarily caused by dysfunction of keratinocytes, psoriasis is now recognized as a complicated immune system disorder that involves the interplay of innate immunity and adaptive immune response [1] — [3].

Epidermal hyperplasia; aberrant keratinocyte proliferation and differentiation; angiogenesis; infiltration of T lymphocytes; dendritic cells and neutrophils; and elements of innate immunity are all thought to contribute to the pathogenesis of the disease [4][5].

Currently, the biologics approved by the US Food and Drug Administration to treat psoriasis target either T cells or TNF-α. Alefacept Amevive®, Astellas Pharma US, Inc.

Efalizumab Raptiva®, Genentech, Inc. Etanercept Enbrel®, Immunex Corporation, Thousand Oaks, CAinfliximab Remicade®, Centocor, Inc. Despite the success of anti—TNF-α therapies, the involvement anti psori recenzii nano psoriazis TNF-α in disease pathogenesis is not yet fully understood.

The limited clinical response associated with some currently available therapeutics and uncertainties regarding the complexity of psoriasis raise the possibility of other factors being implicated in the pathogenesis.

IL is a key inducer of IFN-γ synthesis in T cells. The activation of IFN-γ signaling in lesional skin of psoriatic patients has been confirmed by genomic profiling [6]. Increased expression of mRNAs encoding p19 and p40 subunits of IL has been found in lesional skin of psoriatic patients [7]. Administration of an anti—p40 antibody to a small number of psoriatic patients click significantly improved clinical activity [8].

Fleisch psoriazis motiv forum der, Mee et al showed that IL-1β was constitutively expressed by keratinocytes in vivo and overexpressed in lesional skin [9]. Boniface et al demonstrated that oncostatin M OSMa member of the IL-6 family of cytokines, was a potent keratinocyte activator similar to TNF-α, IL-1, IL, and IL They also showed that OSM was associated with cutaneous inflammatory responses [10].

IL, an effector cytokine mainly produced by T cells, and IL were found to mediate cross talk between the immune system and epithelial cells and might have essential functions in host defense and the pathogenesis of psoriasis [11].

It remains to be seen whether drugs directed at these potential therapeutic Casey privind tratamentul psoriazisului translate to meaningful clinical response rates in psoriasis patients. Given the limited benefit and lack of mechanistic understanding of currently approved TNF-α blockers, as well as the preliminary nature of the studies of additional molecules, we wanted to identify other factors that might contribute to the pathogenesis of disease.

Such factors could represent additional therapeutic opportunities. For the anti psori recenzii nano psoriazis time, we used the Affymetrix® whole genome U plus v2. To identify characteristics of cutaneous alterations specific to psoriasis, we used an Affymetrix human genome U plus v2.

Probe-level summaries were calculated using the GC-RMA normalization algorithm in Stratagene's ArrayAssist® Lite software package. Significance analysis anti psori recenzii nano psoriazis microarrays with control of the anti psori recenzii nano psoriazis discovery rate see Materials and Methods was used to select differentially regulated genes in psoriasis pairwise unguent cu psoriazis plantar among lesional and nonlesional skin, lesional skin and skin from healthy donors, and nonlesional and skin from healthy donors.

Overall, we observed that probe sets were up-regulated and probe sets were down-regulated in lesional skin compared with nonlesional skin. Although the number of down-regulated genes outnumbered the up-regulated genes in lesional skin, the up-regulated comentarii lipitori in psoriazis de anti psori recenzii nano psoriazis showed a much larger magnitude of differential regulation overall.

Subsequently, our analysis focused mostly on the up-regulated genes. Additionally, we observed that probe sets were up-regulated and probe sets were down-regulated in nonlesional skin compared with skin from healthy donors. The genes differentially regulated in nonlesional skin are mostly distinct from those altered in lesional skin. Figure 1 shows a Venn diagram of the probe sets altered in lesional skin and nonlesional skin. Only 36 of the up-regulated probe sets in lesional skin were also up-regulated in nonlesional skin.

Similarly, only 43 of the probe sets down-regulated in lesional skin were also down-regulated in nonlesional skin. Taken together, these anti psori recenzii nano psoriazis suggest that the molecular click the following article and biological changes from nonlesional skin anti psori recenzii nano psoriazis lesional skin are mainly distinct from the differences between normal and nonlesional skin.

Venn diagram illustrates the number of probe sets that show altered expression at the mRNA level in all three combinations of lesional skin, nonlesional skin, and skin from healthy donors.

Values shaded in red indicate the number of probe sets significantly up-regulated; values shaded anti psori recenzii nano psoriazis green indicate the number of probe sets significantly down-regulated. The intersecting regions represent probe sets that are common to the specific comparisons. Of the genes up-regulated in lesional skin, CD4, CD69, IL-7R, and IL-2Rγ are T cell markers; CXCL9, CXCL10, CXCL11, CCL18, CCL19, and CCR7 are involved in T cell trafficking and recruitment; LAMP3, CD83, CD, CD53, and CD24 are dendritic cell surface markers; IL-1β, IRAK2, IL-1F5, IL-1F6, and IL-1F9 are IL-1—inducible genes; IL-8 is a neutrophil-chemotactic factor whose production can be induced by IL-1, TNF-α and OSM.

The strong overexpression of SA family members and DEFB4 in lesional skin could result from both neutrophil infiltration and keratinocyte activation. Overall, these observations agree with the well-known presence of T cells, dendritic cells, and neutrophils in lesional skin of psoriatic patients. It is also worth noting that IL-8 mRNA is highly up-regulated in lesional skin, whereas it is slightly down-regulated in nonlesional skin compared with skin from healthy donors Table S1.

This observation suggests an increase of neutrophil activity in lesional skin of psoriatic patients. Many of the genes downregulated in nonlesional skin compared to normal skin are transcription factors such as JUN, JUNB, FOSB, ATF3, NR4A2, PER1, EGR1, MAFF Table S3.

This finding suggests that nonlesional skin, although overtly normal, has readily identifiable alterations at anti psori recenzii nano psoriazis transcript level.

In contrast, the most downregulated genes in lesional skin compared to nonlesional skin include genes that encode structural, cell adhesion and tight junction proteins such as CLDN8, KRT1B, CNTNAP3B, PCDH21, PAPLN; immune response genes such as IL1F7, CCL27, F3; and genes involved in signaling pathways such as WIF1, ADRB2, TIMP3 Table S2. To identify the signaling pathways altered in psoriasis, we performed an analysis using the GeneGo MetaCore pathway and network approach see Materials and Methods.

All the putative signaling pathways activated were cytokine- and chemokine-mediated signaling pathways or were involved in immune responses. For example, in agreement with the literature [10][12]IFN-γ, TNF-α, and OSM signaling anti psori recenzii nano psoriazis were activated in lesional skin of psoriatic patients. Components of the click at this page, such as IFNAR1, IFNAR2, STAT1, IRF1, MPL, ISG15, and IFI6, were all significantly overexpressed in lesional skin compared with nonlesional skin of psoriatic patients.

WNT, PTEN, PDGF, ESR1 and several cell adhesion pathways ist din plăci psoriazice des among the most significantly suppressed pathways in lesional skin compared to nonlesional skin of psoriatic patients.

Pathway image was generated with GeneGo's MetaCore integrated software anti psori recenzii nano psoriazis. Individual symbols within the image represent well—characterized proteins or protein complexes.

Arrows linking the proteins represent the stimulatory, inhibitory, or interactive effect of the protein on the target protein. Thermometers adjacent to the individual symbols represent relative expression levels red indicates overexpression; blue indicates underexpression of transcripts that encode the protein or protein complex within the particular pathway.

To determine the prevalence anti psori recenzii nano psoriazis magnitude of the overexpression of type I IFN—inducible genes in psoriasis, we first carried out ex vivo stimulation of healthy donor whole blood and in vitro stimulation of normal human keratinocytes with different members of the type I IFN family see Materials and Methods and Supplemental Material to identify type I IFN—inducible genes.

We observed probe sets about 1. A total of probe sets were down-regulated by IFN-α or IFN-β in the same experiment. In keratinocytes, many of these genes i. The top 50 probes upregulated by leukocyte IFN are listed in Table S4. The probes upregulated by IFN-α2a are similar to those by leukocyte IFN data not shown. From the list of probe sets that were identified to be type I IFN—inducible from the ex vivo stimulation studies, we identified of probe sets We also observed that 19 of the top Table S1 anti psori recenzii nano psoriazis up-regulated probe sets in lesional skin were type I Anti psori recenzii nano psoriazis genes, indicating an enrichment of type I IFN—inducible genes among the most overexpressed genes in lesional skin of psoriatic patients.

Table 1 lists the top 50 most up-regulated type I IFN—inducible genes expressed sequence tags [ESTs] and hypothetical proteins are excluded from the anti psori recenzii nano psoriazis in lesional skin of psoriatic patients. Next, we asked whether type I IFN—inducible genes are also significantly overexpressed in nonlesional skin of psoriatic patients compared with skin from normal donors. From Table 1we observe that for those genes up-regulated in lesional skin compared with nonlesional skin in psoriatic patients, nearly anti psori recenzii nano psoriazis are expressed at similar levels in nonlesional skin compared with skin from healthy donors several genes [eg, RGS1 here SPTLC2] are down-regulated in anti psori recenzii nano psoriazis skin compared with skin from healthy donors.

Figure 3 shows the relative expression of 3 type I IFN—inducible genes HPSE, OASL, and HERC6 and 1 gene that is not IFN—inducible SERPINB4 in lesional skin compared with nonlesional skin, and in nonlesional skin compared with skin from healthy donors.

The expression of these genes in lesional skin compared with nonlesional skin is statistically significant, and on average, and fold higher, whereas the mRNA levels of these genes remain unaltered in nonlesional skin compared with skin from healthy donors.

Shown are three type I IFN—inducible genes HPSE, OASL, and HERC6 and 1 gene that is not type I IFN—inducible SERPINB4 in lesional skin LS compared with nonlesional skin NS in psoriatic patients, and in NS compared with skin from healthy donors NN based on microarray data. The fold changes of these genes in LS are compared with their paired NS, and Anti psori recenzii nano psoriazis is compared with the average of 21 NN controls. The horizontal bars represent the average fold change.

The P values for the relative expression of HPSE, OASL, HERC6, and SERPINB4 between NS and NN, and between LS and NS are listed in pairs: Figure 4A psoriazis seboreea smântână și a heat map of unsupervised hierarchical clustering of the up-regulated type I IFN—inducible probe sets in all lesional and nonlesional skin from psoriatic patients and skin from healthy donors.

These samples segregate into 2 large clusters: This observation demonstrates that the magnitude of the overexpression of type I IFN—inducible genes in lesional skin is distinct from that in nonlesional skin or skin from healthy donors. A, Hierarchical clustering of all psoriasis samples profiled blue: Each row corresponds to a single probe set; each column corresponds to a single sample. Branch lengths indicate the degree of similarity with joined samples, with a longer branch indicating a less similarity between joined samples.

Red represents up-regulation vs control ie, average expression of 21 normal samplesand green represents down-regulation vs control. B, 3-dimensional PCA plot of all psoriasis samples profiled using the up-regulated type I IFN—inducible probe sets in lesional skin compared with those in anti psori recenzii nano psoriazis paired nonlesional skin.

Each point represents 1 sample blue: Figure 4B shows the principal components analysis PCA plot of the same samples shown in Figure 4A using the same type I IFN—inducible probe sets. PCA is a mathematical calculation that reduces the dimensionality of the data set so that each individual sample can be viewed in a 2- or 3-dimensional plot. Skin biopsies from healthy donors and nonlesional skin biopsies are mostly clustered together, which suggests that they have comparable level of expression of type I Anti psori recenzii nano psoriazis genes.

Furthermore, the analysis shows that the majority of lesional skin biopsies clearly separate from normal and nonlesional skin biopsies. This indicates that most of these patients had overexpression of the type I IFN—inducible genes, and that was distinct from those in the other 2 groups. Three lesional skin biopsies are close to the nonlesional skin and skin from healthy donors group in the PCA plot.

These 3 samples were from the 3 psoriatic patients that had weaker overexpression of type I IFN—inducible genes compared with the rest of the psoriatic patients in the study. We then asked whether the observed overexpression of the type I IFN—inducible genes in psoriatic patients from microarray studies could be confirmed by a second platform. Lesional and nonlesional skin biopsy pairs from 18 psoriatic patients, along with pooled biopsies from healthy donors, were assayed for the relative expression of mRNA of 40 genes 29 genes were type I IFN—inducible; the other 11 genes were among the most up-regulated in lesional skin of psoriatic patients.

These genes were selected based on their prevalence and magnitude of overexpression in lesional skin biopsies. The overexpression of all genes in lesional skin was confirmed by Shin râios picioare QRT-PCR. In the majority of the genes, good correlation between microarray and TaqMan assays was observed [13]. Overall, these observations further substantiate that type I IFN—inducible genes are significantly overexpressed in lesional skin of psoriatic patients but not in nonlesional skin of patients or skin from normal donors.

Given that we observed significant overexpression of type I IFN—inducible genes in lesional skin of psoriatic patients, we wanted to characterize the type I IFNs that may be responsible. As reported previously, we were not able to detect IFN-α proteins in skin from healthy donors or stable psoriatic skin [14]. Schmid et al [15] were able to use in situ hybridization to weakly detect IFN-α mRNA throughout the hyperkeratotic epidermis.

However, they could not detect IFN-β, most likely because of the sensitivity limitation in their measurements. We used the TaqMan Low Density Array TLDA technology a TaqMan QRT-PCR—based assay from Applied Biosystems to measure the mRNA level of type I IFN family members in paired lesional skin and nonlesional skin from 18 different psoriatic patients, together with RNA from 2 of the healthy donor skin biopsies.

Genes that represent anti psori recenzii nano psoriazis IFN-α subtypes 1, 2, 5, 6, 7, 8, 14, 17 and 21; the primers for 4 anti psori recenzii nano psoriazis IFN-α subtypes were not availableIFN-β, -κ, -ω, IFNAR1, and IFNAR2 were printed on the array. The relative overexpression of mRNA of 9 IFN-α subtypes in lesional skin compared with either nonlesional skin or skin from anti psori recenzii nano psoriazis donors is shown in Figure 5A.

However, all of these IFN-α subtypes were up-regulated at the mRNA level in lesional skin compared with that in skin from healthy donors. The overexpression of the mRNAs of other members of the type I IFN family, IFN-β, -κ, and —ω in lesional skin compared with nonlesional anti psori recenzii nano psoriazis or skin from healthy donors is shown in Figure 5B. The alterations of IFN-β and IFN-ω mRNAs in nonlesional skin were not significant.

IFN-κ mRNA was up-regulated by approximately 1. Although IFNAR2 up-regulation was significant in nonlesional skin, up-regulation of IFNAR1 was not Figure 5C. Collectively, these data provided evidence that mRNA levels for most type I IFN family members were comparable between nonlesional skin and skin from healthy donors with the exception of IFN-α5 and IFN-κ and were significantly increased in lesional skin of psoriatic patients.

Selected mRNAs include A Type I IFN-α subtypes box plotB other Type-I IFNs, and C IFN-α receptors in lesional skin LS or nonlesional skin NS compared with skin from healthy donors NN. Horizontal bars represent median fold change. The P values for the overexpression of these genes in NS or LS vs NN listed in pairs are as follows: T cells contribute to the development of diseased skin in psoriasis and to the epidermal hyperproliferation in genetically predisposed individuals through the secretion of Th1 cytokines.

Since biologics that target T cells anti psori recenzii nano psoriazis TNF-α show clinical benefit in psoriasis, we addressed the involvement of IFN-γ and TNF-α in the pathogenesis of the disease. As mentioned earlier, we observed the activation of both the IFN-γ and TNF-α signaling pathways in lesional skin of psoriatic patients. We used TLDA to measure the mRNA levels of IFN-γ, IFNGR1, IFNGR2 and TNF-α in lesional and nonlesional skin from psoriatic patients and compared them with those from healthy donors.

These results show that expression of mRNA for IFN-γ and TNF-α is different from that of type I Http://mycakefinancialmanagement.co.uk/pret-de-droguri-psoriazis.php family members.

Relative expression of mRNA and median fold changes of in lesional skin LSor nonlesional skin NS compared with skin from healthy donors NN are shown. The averages of the relative mRNA levels of these cytokine and their receptors in NN from 2 donors were scaled to 1 based on TaqMan QRT-PCR assays.

The horizontal bars represent the median fold change. The P values for the overexpression of these individual genes in NS or Anti psori recenzii nano psoriazis read article with NN listed in pairs are as follows: The ex vivo stimulation of healthy donor whole blood and in vitro stimulation of keratinocytes with IFN-γ and TNF-α was used to identify genes induced by these cytokines.

A total of and probe sets were up-regulated by IFN-γ and TNF-α, respectively, by at least 2-fold in the whole blood anti psori recenzii nano psoriazis all 4 donors challenged for 4 hours. Of the probe sets that were up-regulated in lesional skin compared with nonlesional skin of psoriatic patients, and 35 of them were IFN-γ and TNF-α—inducible, respectively Figure 7.

Venn diagrams illustrating both the number of probe sets that are altered by type I IFN, IFN-γ, and TNF-α in ex vivo stimulation geringerer piscină psoriazis Ruit whole blood from healthy donors left circles and probe sets that are altered in lesional skin compared with nonlesional skin right circles.

The anti psori recenzii nano psoriazis regions represent the probe sets that are common to anti psori recenzii nano psoriazis comparisons. Type I IFN, IFN-γ, and TNF-α—inducible probe sets identified in the ex vivo study allowed us to identify the type I IFN, IFN-γ, and TNF-α—inducible genes in each lesional skin biopsy compared with paired nonlesional biopsies that were up-regulated by at least 2-fold.

Figure 8A shows the number of type I IFN, IFN-γ, and TNF-α—inducible genes up-regulated in each of the 26 paired lesional and nonlesional skin biopsies.

The ceai psoriazis of IFN-γ and TNF-α—inducible genes in a given lesional skin biopsy positively donjeg simptomelor psoriazisului si tratament School with the number of type I IFN—inducible genes in the same sample. This anti psori recenzii nano psoriazis was confirmed by the strong correlation in the coactivation of these 3 sets of genes with correlation coefficients of at least 0.

Paired lesional and nonlesional skin of psoriatic patients was analyzed with Affymetrix Genechip®. The type I IFN, IFN-γ and TNF-α—inducible genes were selected based on healthy donor whole blood ex vivo stimulation with these cytokines. B, The numbers of type I IFN—, IFN-γ— and TNF-α—inducible genes in lesional skin compared with nonlesional skin are significantly different as evident from pairwise comparisons. The horizontal bars represent the median value for each group.

A similar analysis was carried out for genes that were down-regulated in lesional skin compared with the nonlesional skin of psoriatic patients Figure 7. Of the probe sets down-regulated in lesional skin, only 17, 5, and 5 of them were type I IFN, IFN-γ, and TNF-α inducible. Somewhat surprisingly we found that although mRNAs of IFN-γ and TNF-α were found to be up-regulated in nonlesional skin of psoriatic patients when compared with those from anti psori recenzii nano psoriazis donors, we did not find that IFN-γ or TNF-α—inducible genes were significantly overexpressed in nonlesional skin data not shown.

The up-regulation of mRNAs of type I IFNs, IFN-γ, and TNF-α, together with the formă exsudativă de psoriazis up-regulation of their respective gene signatures in psoriatic lesional skin, suggests the presence of type I IFNs, IFN-γ, and TNF-α protein and active signaling in skin lesions.

In contrast, the elevated expression of mRNAs of IFN-γ and TNF-α anti psori recenzii nano psoriazis nonlesional skin does not result in corresponding up-regulation of IFN-γ or TNF-α—inducible genes. This suggests that IFN-γ and TNF-α proteins are not more info in nonlesional skin or that other signaling molecules anti psori recenzii nano psoriazis have inhibitory effects on the IFN-γ and TNF-α pathways in nonlesional skin of psoriatic patients.

To determine whether the highly overexpressed type I IFN—inducible genes in psoriatic skin gave rise to similar changes in the expression of the proteins, immunohistochemical analyses were carried out to assess the presence of 2 type I IFN—inducible proteins, STAT1 and ISG15, in skin from the same patients and the same biopsy samples that underwent whole genome array analysis as described above.

Of the 16 pairs of lesional and nonlesional skin biopsies, 6 pairs showed increased numbers of pDCs, and 9 pairs showed increased numbers of mDCs in lesional skin compared with nonlesional skin. CD31 was used as a positive tissue control, to demonstrate that expressed epitopes in the skin cryosections could be detected by immunohistochemical staining Figure 9. BDCA2 is a specific marker for pDCs, which are present at greater numbers in lesional skin inset is × compared with nonlesional skin, and not at all in skin from healthy donors.

CD83 is a marker for mDCs; CD4 anti psori recenzii nano psoriazis present on Anti psori recenzii nano psoriazis cells and dendritic cells. STAT1 protein staining was observed in the epidermis of lesional skin both nuclear and cytoplasmic and dermal mononuclear inflammatory cells, but not in nonlesional or skin from healthy donors.

ISG15 protein increase was observed in psoriatic lesional skin and to a lesser extent in nonlesional skin but was not detected in the dermis of healthy donors. Type I IFNs are produced in response to viral and bacterial infections and play a key role in host defense mechanisms. They stimulate the maturation of pDCs learn more here the generation and function of natural killer NKT, and B cells [16][17].

The type I IFN family is composed of several family members 13 IFN-α subtypes, IFN-β, -ω, -κ, -σ, -δ, -λ ; IFN-α and IFN-β are anti psori recenzii nano psoriazis most abundant. IFN-γ, a type II IFN, is mainly produced by activated T cells, dendritic cells, and NK cells and is involved in adaptive immune responses. IFNs have long been associated with anti psori recenzii nano psoriazis pathogenesis of psoriasis.

IFN pathways are active in psoriatic lesions [18][19]. Treatment of non-psoriatic disease with IFN can induce or exacerbate psoriasis [20] — [23]as can treatment with imiquimod, a toll-like receptor agonist that induces production of type I IFNs from pDCs [24]. Disruption of IFN-α signaling or the inhibition of the ability of pDCs to produce IFN-α prevented the T tratament remedii psoriazis și de de cauzele populare simptomele development of psoriasis, [26].

Thus, pDC-derived IFN-α is both necessary and sufficient for disease manifestation in this model; however, confirmatory human data is lacking. Microarray anti psori recenzii nano psoriazis of disease tissues has widely been used to identify etiopathogenic factors of disease activity, and previous studies have used microarray analyses to profile lesional skin and nonlesional skin from psoriatic patients [7][27].

However, neither of these studies was performed using a whole genome array platform. Furthermore, the first study lacked skin from healthy donors as a control and was carried out on a limited number of patient samples. The second study focused mainly on T cell and dendritic cell activation in lesional skin of psoriatic patients. The data described here represent the first large-scale study on human samples that demonstrates the prevalence of type I IFNs and type I IFN—inducible genes in psoriatic skin.

Of the type I IFN—inducible genes overexpressed in anti psori recenzii nano psoriazis skin of psoriatic patients, STAT1 is a key component in forming the ISGF3 complex. ISGF3 is the heterotrimeric transcriptional factor complex that is formed upon the activation of the anti psori recenzii nano psoriazis I IFN receptor. It is composed of phosphorylated STAT1, STAT2, and IRF9. Upon translocation to the nucleus, this complex is capable of activating the transcription of type I IFN—inducible genes [28].

IRF1 functions as a transcriptional activator for the type I IFN—inducible genes [31]. MX1, MX2, and OAS family members OAS1, OAS2, OAS3 mediate resistance to virus infection. USP18, UBE2L6, and HERC5 are all members of the ISG15 signaling pathways. LAMP3 and CD83 are anti psori recenzii nano psoriazis cell—marker genes. We also showed that mRNAs of TNF-α and TNF-α—inducible genes are overexpressed in lesional skin of psoriatic patients, which may shed light on why anti—TNF-α therapy provides clinical benefit to psoriatic patients.

Type I IFNs may provide the link between innate and adaptive immune responses. They are secreted by pDCs in response to environmental factors like mechanical stress and infections of the skin 2 of the common triggers that cause disease relapse ,and drive the activation and expansion of pathogenic T cells leading to psoriasis [24][26].

Our observations support this link. For example, the presence of pDCs and mDCs and the up-regulation of mRNAs of type Anti psori recenzii nano psoriazis IFN members in lesional skin suggest the overexpression of type I IFN proteins at these sites.

Type I IFNs can facilitate activation of mDCs and promote T cell polarization to proinflammatory Th1 effectors [33]. The mRNA for IL-8, a key anti psori recenzii nano psoriazis for neutrophils, and IFN-γ and TNF-α—inducible genes are not overexpressed in nonlesional skin compared with skin from healthy donors.

However, all of these genes are overexpressed in lesional skin in a similar manner to the anti psori recenzii nano psoriazis of mRNAs of type I IFN family members and type I IFN—inducible genes. It remains unclear as to whether IFN-α signaling occurs upstream or downstream of IFN-γ and TNF-α signaling.

Ongoing genomic studies for anti IFN-α mAb trial in psoriasis from our laboratory will clarify this issue in the near future. Type I IFN has been implicated to be involved in the pathogenesis of other autoimmune diseases like systemic lupus erythematosus SLEtype I diabetes, rheumatoid arthritis, myositis, and Sjögren's syndrome [34] — [36]. The click here study demonstrates the utility of analysis of tissues from disease sites using microarray and immunohistochemistry to unveil potential mediators of the pathogenesis of psoriasis.

This approach has been successfully used to show the involvement of type I IFNs in the pathogenesis of SLE and myositis [35][37][38]. The identification of anti psori recenzii nano psoriazis overexpression of mRNA of TNF-α and TNF-α—inducible genes in lesional skin of psoriatic patients and the therapeutic benefit of anti—TNF-α therapies in psoriasis provide further support of using the microarray approach to identify potential therapeutic targets for diseases.

The anti psori recenzii nano psoriazis of type I IFN—producing anti psori recenzii nano psoriazis, overexpression of mRNAs of type I IFNs and type I IFN—inducible genes and proteins in lesional skin of psoriatic patients provide a strong rationale for investigating type I IFNs as new therapeutic anti psori recenzii nano psoriazis for the treatment of psoriasis. A total of 21 biopsies from healthy donors 5 samples were obtained from Biochain, 14 samples were from ILSBio, and 2 samples were from Dr.

James Krueger, Rockefeller University, New York, NY26 paired nonlesional and lesional all were plaque-type skin biopsies from 26 psoriatic patients 21 pairs from Asterand, 5 pairs from Dr. Kruegerand 5 lesional skin biopsies from 3 psoriatic patients all plaque-type tratate psoriazis în Thailanda profiled using the Affymetrix® whole genome array.

All the donors who gave biopsy tissue both healthy controls and individuals with psoriasis gave written informed consent for the tissue to be taken and used in this study. Human specimens used in this paper that were procured from both registered commercial vendors and Dr. Krueger at Rockefeller University obtained IRB approval from their respective branches to collect samples. Ex vivo stimulation of whole blood was conducted on blood collected from 3 or 4 donors MedImmune, Inc.

Blood samples were exposed to treatments of vehicle 1× PBSa panel of IFN-α subtypes IFN-α2a, -4b, -5, -6, -7, -8,IFN-β, IFN-ω, IFN-λ, IFN-γ, leukocyte IFN, or TNF-α at concentration of 3xEC The PAXgene tubes were incubated at room temperature for 2 hours and then frozen until processed.

All the blood donors gave written informed consent for the blood to be taken and used in this study. Normal human keratinocytes EpiDerm system, MatTek, Inc. Epidermal cultures were harvested at 4 hours post-treatment for transcript analysis. Total RNA was extracted from PAXgene blood and skin biopsies using the PAXgene Blood RNA kit and the Qiagen RNeasy Fibrous Tissue Mini kit Hilden, Germanyrespectively.

RNA quality was assessed on an Agilent Bioanalyzer using the RNA Nano LabChip®. The generation of biotin-labeled amplified cRNA from 2 µg of total RNA was accomplished with the Affymetrix GeneChip® One-Cycle cDNA Synthesis kit and the Affymetrix GeneChip® IVT Labeling kit.

The concentration and purity of the cRNA product were determined spectrophotometrically. Twenty micrograms of each biotin-labeled cRNA was fragmented for hybridization on Affymetrix Human Genome U Plus 2. All GeneChip® washing, staining, and scanning procedures were performed with Affymetrix standard equipment. Data capture and initial array quality assessments were performed with the GeneChip Operating Software GCOS tool. Stratagene's La Jolla, CA ArrayAssist® Lite software was used to calculate probe-level summaries GC-RMA from the array CEL files.

R packages R Development Core Team samr and qvalue were used to identify differentially regulated genes. PCA and hierarchical clustering analyses were performed with SpotFire http: The microarray data reported in this manuscript is MIAME-compliant and is available at: All authors in the manuscript have access to all data and act as guarantor for the analysis and the manuscript overall. TLDA from Applied Biosystems was used to determine the fold-change differential for a panel of genes between paired lesional skin and nonlesional skin from psoriatic patients.

Genes printed on the array included 9 type I IFN-α subtypes 1, 2, 5, 6, 7, 8, 14, 17, and 213 additional type I IFNs IFN-β, -κ, -ωIFN-γ, IFNAR1, IFNAR2, IFNGR1, IFNGR2, and TNF-α.

Double-stranded cDNA for each patient sample was preamplified for 10 cycles using the TaqMan PreAmp Master Mix kit Applied Biosystems. Standard procedures for loading the array were then followed and the array was run on a HT Fast Real-Time PCR System Applied Biosystems.

Data analysis of the resulting Ct values was conducted with SDSv2. A mixture of 43 TaqMan Gene Expression assays Applied Biosystems was prepared click here not included using anti psori recenzii nano psoriazis TaqMan PreAmp Master Mix Kit Applied Biosystems. A total of 44 samples were run in triplicate using 3 different BioMark Real-Time PCR Systems against a set of 48 TaqMan Gene Expression Assays in BioMark The normal controls were included on every array.

Three identical dynamic arrays were prepared in parallel for each set of 16 samples totaling 9 dynamic arrays. Dynamic arrays were loaded using a NanoFlex 4-IFC Controller Fluidigm Corpand real-time reactions were performed and analyzed using BioMark Real-Time PCR System and Analysis software Fluidigm Corprespectively. Anti psori recenzii nano psoriazis were calculated for each set of 3 replicate reactions and then averaged for each dynamic array.

Anti psori recenzii nano psoriazis above 20 were excluded from the calculation. Delta-delta Cts ΔΔCt were calculated using the mean of the 4 reference genes GAPDH, TFRC, β2M, and 18S and a calibrator sample and were converted to fold expression anti psori recenzii nano psoriazis by the following formula: One half of each frozen psoriatic, nonlesional, and healthy donor biopsy was embedded in optimum cutting temperature OCT compound sectioned at 5 µm, mounted on charged anti psori recenzii nano psoriazis Mercedes Medical, FLand fixed in cold acetone.

Incubation with primary antibodies was performed as follows: Slides were counterstained with hematoxylin, dehydrated, and cover slipped. Figure S1 shows hierarchical clustering of probe sets differentially regulated by IFN-α subtypes, IFN-β, IFN-γ, and TNF-α in whole blood ex vivo stimulation experiment. Table S1 lists the top probe sets up-regulated in lesional skin compared with nonlesional skin in psoriasis.

Table S2 lists the top 50 probe sets down-regulated in lesional skin compared with nonlesional skin in psoriasis. Table S3 lists the top 50 probe sets down-regulated in nonlesional skin compared with skin from healthy donors. Table S4 lists the top 50 probe sets up-regulated from the in vitro stimulation of normal human keratinocytes with leukocyte IFN. Online supplemental material is available this web page http: Fold change fc; log2 transformed and q Value calculated by FDR of the top probe sets up-regulated in anti psori recenzii nano psoriazis skin anti psori recenzii nano psoriazis with nonlesional skin in psoriasis.

Also listed are the log2 transformed fold change and q values of these genes when comparing nonlesional skin with normal skin from healthy click at this page. Type I IFN-inducible genes are designated by the IFNI column. The table is available at: Fold change fc; log2 transformed and q Value calculated by FDR of the top 50 probe sets down-regulated in lesional skin compared with nonlesional skin in psoriasis.

Also listed are the log2 transformed fold change and q Values of these genes when comparing nonlesional skin with normal skin from healthy donors. All data was GC-RMA normalized. Fold change fc; log2 transformed and q Value calculated by FDR of the top 50 probe sets down-regulated in nonlesional skin compared with skin from healthy donors. Also listed are pentru Premiul psoriazis Nobel log2 transformed fold change and q values of these genes when comparing nonlesional skin with lesional skin.

Fold change fc; log2 transformedP values, and mean signal intensities http://mycakefinancialmanagement.co.uk/psoriazis-arata-ca-la-etapa-iniial-de-pe-picior.php the top 50 anti psori recenzii nano psoriazis sets up-regulated from the in vitro stimulation of normal human keratinocytes with leukocyte IFN. Normal human keratinocytes were stimulated with human leukocyte IFN.

Replicates of three were run for both the untreated samples and the stimulated samples. A paired Student's t-test was used to calculate the P values. Hierarchical clustering of probe sets differentially anti psori recenzii nano psoriazis by IFN-α subtypes and IFN-β pinkIFN-γ blueand TNF-α brown in whole blood ex vivo stimulation experiment see Materials and Methods.

Each role corresponds anti psori recenzii nano psoriazis a single probe set, while each column corresponds to a single sample. Color represents relative expression level of individual probe set as compared with the average expression of the no treatment controls black. Red represents up-regulation versus control, green down-regulation versus control, while black indicates no Cel mai bun pentru psoriazis. The authors would like to acknowledge Wendy Trigona and Wendy White for procuring skin biopsies of psoriatic patients from commercial vendors for the study; Philip Brohawn, Martha Wester, Nancy Huddy, Karma DaCosta, Chad Morris, Ricardo Cibotti, Bonnie Swerdlow, and Jennifer Reed for providing technical assistance; Rakesh Dixit and Wendy White for providing critical review of the manuscript.

The authors would also like to acknowledge Chris Heid, Martin Pieprzyk, Mike Lucero, and John Lynch from Fluidigm Corporation for their assistance with large-scale TaqMan QRT-PCR assays. Conceived and designed the experiments: LR CM Md AB.

YY LR BWH AC PAK BJ. Is the Subject Area "Biopsy" applicable to this article? Is the Subject Area "Psoriasis" anti psori recenzii nano psoriazis to this article? Is the Subject Area "Hyperexpression techniques" applicable to this article? Is the Subject Area "T cells" applicable to this article? Is the Subject Area "Keratinocytes" applicable to Tratamentul un nou medicament article?

Is the Subject Area "Pathogenesis" applicable to this article? Is the Subject Area "Skin diseases" applicable to this article? Is the Subject Area "Cytokines" applicable to this article? PLOS is a anti psori recenzii nano psoriazis c 3 corporation, C, and is based in San Francisco, California, US. PLOS ONE Publish Submissions Getting Started Submission Guidelines Figures Tables Supporting Information LaTeX Revising Your Manuscript Submit Now Policies Best Practices in Research Reporting Human Subjects Research Animal Research Competing Interests Disclosure of Funding Sources Licenses and Copyright Data Availability Materials and Software Sharing Ethical Publishing Practice Authorship Downloads and Translations Manuscript Review and Publication Criteria for Publication Editorial and Peer Review Process Anti psori recenzii nano psoriazis Guidelines Accepted Manuscripts Corrections and Retractions Comments Article-Level Metrics Submit Your Manuscript Discover a faster, simpler path to publishing in a high-quality journal.

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Save Total Mendeley and CiteULike bookmarks. Citation Paper's citation count computed anti psori recenzii nano psoriazis Scopus. View Sum of PLOS and PubMed Central page views and downloads. Share Sum of Facebook and Twitter activity. Open Access Peer-reviewed Research Article. Yihong Yao,  Laura Richman,  Chris Morehouse,  Melissa de los Reyes,  Brandon W. Higgs,  Anmarie Boutrin,  Barbara White,  Anthony Coyle,  James Krueger,  Peter A.

Reader Comments 1 Media Coverage Figures. All Figures Next Previous. Correction 13 Mar Abstract Background Psoriasis is an immune-mediated disease characterized by aberrant epidermal differentiation, surface scale formation, and marked cutaneous inflammation.

Geraldine Butler, University College Dublin, Ireland Received: July 16, Copyright: Probe sets found to be altered using microarray analysis. Type I IFN signaling pathway activated in lesional skin of psoriatic patients.

Type I IFN—inducible genes are overexpressed in lesional skin of psoriatic patients To determine the prevalence and magnitude of the overexpression of type I IFN—inducible genes in psoriasis, we first carried out ex vivo stimulation of healthy donor whole blood and in vitro stimulation of normal human keratinocytes with different members of the type I IFN family see Materials and Methods and Supplemental Material to identify type I IFN—inducible genes.

Fold Changes fc; log 2 transformed and q Values Calculated by FDR for the Top 50 Most Up-regulated Type I IFN-Inducible Genes in Psoriatic Lesional Skin Versus Nonlesional Skin. Type I IFNs, IFNAR1, and IFNAR2 mRNA are up-regulated in lesional skin as compared with nonlesional skin and skin from healthy donors Given that we observed significant overexpression of type I IFN—inducible genes in lesional skin of psoriatic patients, we wanted to characterize the type I IFNs that may be responsible.

Relative expression and median fold changes of select mRNAs. Co-overexpression of type I, type II IFN, and TNF-α and their gene signatures in lesional skin of psoriatic patients T cells contribute to the development of diseased skin in psoriasis and to the epidermal hyperproliferation in genetically predisposed individuals through the secretion of Th1 cytokines. Changes in expression of TNF-α, IFN-γ, and IFN-γ receptors.

Probe sets common to lesions and ex vivo stimulation. Co-overexpression of type I IFN, IFN-γ and TNF-α—inducible genes. Immunohistochemical analysis of psoriatic, nonlesional skin, and skin from healthy donors To determine whether the highly overexpressed type I IFN—inducible genes in psoriatic skin gave rise to similar changes in the expression of the proteins, immunohistochemical analyses were carried out to assess the presence of 2 type I IFN—inducible proteins, STAT1 and ISG15, in skin from the same patients and the same biopsy samples that underwent whole genome array analysis as described here. Immunohistochemical analyses of biopsies from psoriatic lesional and nonlesional skin and skin just click for source normal donors.

Discussion Type I IFNs are produced in response to viral and bacterial infections and play a key role in host defense mechanisms. Materials and Methods Patients and Controls A total of 21 biopsies from healthy donors 5 samples were obtained from Biochain, 14 samples were from ILSBio, and 2 samples were from Dr. Ex vivo stimulation of whole blood from healthy donors Ex vivo stimulation of whole blood was conducted on blood collected from 3 or 4 donors MedImmune, Inc.

In vitro stimulation of normal human keratinocytes with type I Și sulfat psoriazis Normal human keratinocytes EpiDerm system, MatTek, Inc. Total RNA extraction and microarray processing Total RNA was extracted from PAXgene blood and skin biopsies using the PAXgene Blood RNA kit and the Qiagen RNeasy Fibrous Tissue Mini kit Hilden, Germanyrespectively.

Microarray data analysis Stratagene's La Jolla, CA ArrayAssist® Lite software was used to calculate probe-level summaries GC-RMA from the array CEL files. Applied Biosystems's TLDA TLDA from Applied Biosystems was used to determine the fold-change differential anti psori recenzii nano psoriazis a panel of genes between paired lesional skin and nonlesional skin from psoriatic patients. Fluidigm's Biomark system Preamplification of cDNA and real-time PCR.

Immunohistochemistry One half of each frozen psoriatic, nonlesional, and healthy donor biopsy was embedded in optimum cutting temperature OCT compound sectioned at 5 µm, mounted on charged slides Mercedes Medical, FLand fixed in cold acetone.

Online supplemental material Figure S1 shows hierarchical clustering of probe sets differentially regulated by IFN-α subtypes, IFN-β, IFN-γ, and TNF-α in whole blood ex vivo stimulation experiment. Acknowledgments The authors would like to acknowledge Wendy Trigona and Wendy White for procuring skin biopsies of psoriatic patients from commercial vendors for the study; Philip Brohawn, Martha Wester, Nancy Huddy, Karma DaCosta, Chad Morris, Ricardo Cibotti, Bonnie Swerdlow, and Jennifer Reed for providing technical assistance; Rakesh Dixit and Wendy White for providing critical review of the manuscript.

Author Contributions Conceived and designed the experiments: Krueger JG The immunologic basis for the treatment of psoriasis with new biologic agents. J Am Acad Dermatol JG KruegerThe immunologic basis for the treatment of psoriasis with new biologic agents. Lebwohl M Psoriasis. Nestle FO, Gilliet M Defining upstream elements of psoriasis pathogenesis: J Invest Dermatol GillietDefining upstream elements of psoriasis pathogenesis: Chamian F, Krueger JG Psoriasis vulgaris: Curr Opin Rheumatol Chamian F, Lowes MA, Lin SL, Lee E, Kikuchi T, et al.

Proc Natl Acad Sci U S A KikuchiAlefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris.

Zhou X, Krueger JG, Kao MC, Lee E, Du F, et al. DuNovel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63,element oligonucleotide array. Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F, et al.

J Exp Med WangIncreased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. Kauffman CL, Aria N, Toichi E, McCormick TS, Cooper KD, et al. ToichiTS McCormickKD CooperA phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL p40 antibody in subjects with plaque psoriasis. Mee JB, Cork MJ, di Giovine FS, Duff GW, Groves RW Interleukin A key inflammatory mediator of psoriasis? JB MeeMJ CorkFS di GiovineGW DuffRW GrovesInterleukin Boniface K, Diveu C, Morel F, Pedretti N, Froger J, et al.

FrogerOncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation. Centre de psoriazis Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, et al. Eastham-AndersonInterleukin, a T H 17 cytokine, mediates ILinduced dermal inflammation and acanthosis. Lew W, Bowcock AM, Krueger JG Psoriasis vulgaris: LewAM BowcockJG KruegerPsoriasis vulgaris: Livden JK, Nilsen R, Bjerke JR, Matre R In situ localization of interferons in psoriatic lesions.

Arch Dermatol Res MatreIn situ anti psori recenzii nano psoriazis of interferons in psoriatic lesions. Schmid P, Itin P, Cox D, McMaster GK, Horisberger MA The type I interferon system is locally activated in psoriatic lesions. J Interferon Res CoxGK McMasterMA HorisbergerThe type I interferon system is locally activated in psoriatic lesions.

Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, et al. NakajimaPlasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K, et al. ShahThe nature of the principal type 1 interferon-producing cells in human blood.

Eriksen KW, Lovato P, Skov L, Krejsgaard T, Kaltoft K, et al. KaltoftIncreased sensitivity to interferon-alpha in psoriatic T cells. Downs AM, Dunnill MG Exacerbation of psoriasis by interferon-alpha therapy for hepatitis C. Clin Exp Dermatol AM DownsMG DunnillExacerbation of psoriasis by interferon-alpha therapy for hepatitis C.

Funk J, Langeland T, Schrumpf E, Hanssen LE Psoriasis induced anti psori recenzii nano psoriazis interferon-alpha. Br J Dermatol SchrumpfLE HanssenPsoriasis induced by interferon-alpha. Ketikoglou I, Karatapanis S, Elefsiniotis I, Kafiri G, Moulakakis A Extensive psoriasis induced by pegylated interferon alpha-2b treatment for chronic hepatitis B. Eur J Dermatol MoulakakisExtensive psoriasis induced by pegylated interferon alpha-2b treatment for chronic hepatitis B.

Pauluzzi P, Kokelj F, Perkan V, Pozzato G, Moretti M Psoriasis exacerbation induced by interferon-alpha. Report of two cases. Acta Derm Venereol MorettiPsoriasis exacerbation induced by interferon-alpha. Gilliet M, Conrad C, Geiges M, Cozzio A, Thurlimann W, et al. ThurlimannPsoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic anti psori recenzii nano psoriazis precursors. Hida S, Ogasawara K, Sato K, Abe M, Takayanagi H, et al.

Nestle FO, Conrad C, Tun-Kyi A, Homey B, Gombert M, et al. GombertPlasmacytoid predendritic cells initiate psoriasis through interferon-alpha production.

Nomura I, Gao B, Boguniewicz M, Darst MA, Travers JB, et al. J Allergy Clin Immunol BoguniewiczMA DarstJB TraversDistinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: Taniguchi T, Ogasawara Anti psori recenzii nano psoriazis, Takaoka A, Tanaka N IRF family of transcription factors as regulators of host defense.

Annu Rev Immunol TanakaIRF family of transcription factors as regulators of host defense. Au WC, Yeow WS, Pitha PM Analysis of functional domains of interferon regulatory factor 7 and its association with IRF WC AuWS YeowPM PithaAnalysis of functional domains of interferon regulatory factor 7 and its association with IRF Honda K, Yanai H, Negishi H, Asagiri M, Sato M, et al.

SatoIRF-7 is the master regulator of type-I interferon-dependent immune responses. Harada H, Willison K, Sakakibara J, Miyamoto M, Fujita T, et al. FujitaAbsence of the type I IFN system in EC cells: Zhao C, Denison C, Huibregtse JM, Gygi S, Krug RM Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways.

GygiRM KrugHuman ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Christensen SR, Shlomchik MJ Regulation of lupus-related autoantibody production and clinical disease by Toll-like receptors.

SR ChristensenMJ ShlomchikRegulation of lupus-related autoantibody production and clinical disease by Toll-like receptors. Bave U, Nordmark G, Lovgren T, Ronnelid J, Cajander S, et al. CajanderActivation of link type I interferon system in primary Sjogren's syndrome: Greenberg SA, Pinkus JL, Pinkus GS, Burleson T, Sanoudou D, et al.

SA GreenbergJL PinkusGS PinkusT. Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, et al. KarypisPM GaffneyWA OrtmannInterferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, et al. BorvakInterferon and granulopoiesis signatures in systemic lupus erythematosus blood. Print Print article EzReprint. Related PLOS Articles Correction: We want your feedback.

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