scholarly journals OP0021 IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN EARLY RHEUMATOID ARTHRITIS PATIENTS RESPONDING TO TOCILIZUMAB

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 12.2-12
Author(s):  
I. Muller ◽  
M. Verhoeven ◽  
H. Gosselt ◽  
M. Lin ◽  
T. De Jong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
T Cells ◽  
Gene Ontology ◽  
Regulatory T Cells ◽  
Early Rheumatoid Arthritis ◽  
Whole Blood ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Double Blind

Background:Tocilizumab (TCZ) is a monoclonal antibody that binds to the interleukin 6 receptor (IL-6R), inhibiting IL-6R signal transduction to downstream inflammatory mediators. TCZ has shown to be effective as monotherapy in early rheumatoid arthritis (RA) patients (1). However, approximately one third of patients inadequately respond to therapy and the biological mechanisms underlying lack of efficacy for TCZ remain elusive (1). Here we report gene expression differences, in both whole blood and peripheral blood mononuclear cells (PBMC) RNA samples between early RA patients, categorized by clinical TCZ response (reaching DAS28 < 3.2 at 6 months). These findings could lead to identification of predictive biomarkers for TCZ response and improve RA treatment strategies.Objectives:To identify potential baseline gene expression markers for TCZ response in early RA patients using an RNA-sequencing approach.Methods:Two cohorts of RA patients were included and blood was collected at baseline, before initiating TCZ treatment (8 mg/kg every 4 weeks, intravenously). DAS28-ESR scores were calculated at baseline and clinical response to TCZ was defined as DAS28 < 3.2 at 6 months of treatment. In the first cohort (n=21 patients, previously treated with DMARDs), RNA-sequencing (RNA-seq) was performed on baseline whole blood PAXgene RNA (Illumina TruSeq mRNA Stranded) and differential gene expression (DGE) profiles were measured between responders (n=14) and non-responders (n=7). For external replication, in a second cohort (n=95 therapy-naïve patients receiving TCZ monotherapy), RNA-seq was conducted on baseline PBMC RNA (SMARTer Stranded Total RNA-Seq Kit, Takara Bio) from the 2-year, multicenter, double-blind, placebo-controlled, randomized U-Act-Early trial (ClinicalTrials.gov identifier: NCT01034137) and DGE was analyzed between 84 responders and 11 non-responders.Results:Whole blood DGE analysis showed two significantly higher expressed genes in TCZ non-responders (False Discovery Rate, FDR < 0.05): urotensin 2 (UTS2) and caveolin-1 (CAV1). Subsequent analysis of U-Act-Early PBMC DGE showed nine differentially expressed genes (FDR < 0.05) of which expression in clinical TCZ non-responders was significantly higher for eight genes (MTCOP12, ZNF774, UTS2, SLC4A1, FECH, IFIT1B, AHSP, and SPTB) and significantly lower for one gene (TND2P28M). Both analyses were corrected for baseline DAS28-ESR, age and gender. Expression of UTS2, with a proposed function in regulatory T-cells (2), was significantly higher in TCZ non-responders in both cohorts. Furthermore, gene ontology enrichment analysis revealed no distinct gene ontology or IL-6 related pathway(s) that were significantly different between TCZ-responders and non-responders.Conclusion:Several genes are differentially expressed at baseline between responders and non-responders to TCZ therapy at 6 months. Most notably, UTS2 expression is significantly higher in TCZ non-responders in both whole blood as well as PBMC cohorts. UTS2 could be a promising target for further analyses as a potential predictive biomarker for TCZ response in RA patients in combination with clinical parameters (3).References:[1]Bijlsma JWJ, Welsing PMJ, Woodworth TG, et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet. 2016;388(10042):343-55.[2]Bhairavabhotla R, Kim YC, Glass DD, et al. Transcriptome profiling of human FoxP3+ regulatory T cells. Human Immunology. 2016;77(2):201-13.[3]Gosselt HR, Verhoeven MMA, Bulatovic-Calasan M, et al. Complex machine-learning algorithms and multivariable logistic regression on par in the prediction of insufficient clinical response to methotrexate in rheumatoid arthritis. Journal of Personalized Medicine. 2021;11(1).Disclosure of Interests:None declared

scholarly journals IFITM1 is differentially expressed in the blood of patients with Crohn’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Regulatory T Cells ◽  
Whole Blood ◽  
Differentially Expressed Gene ◽  
Differentially Expressed ◽  
Interferon Signaling ◽  
Oligoadenylate Synthetase

The interferon pathway (1) is an innate immune signaling system that evolved to protect multicellular organisms from viral infections (2). The expression of multiple gene families is expressed following activation of interferon signaling (1); one of these is the antiviral interferon inducible transmembrane proteins, or IFITM gene family (3). Using publicly available datasets (4, 5), we identified the interferon induced transmembrane protein 1, IFITM1 (6-10), as a differentially expressed gene in the whole blood and CD4+ CD25+ regulatory T-cells of patients with Crohn’s Disease. IFITM1 was expressed at significantly higher levels in the whole blood and Treg of patients with Crohn's Disease than in non-affected control subjects. We previously reported that changes in gene expression of the double stranded ribonucleic acid sensor, 2’-5’-oligoadenylate synthetase, OAS2, were among the most significant quantitive differences in the gene expression of monocyte-derived macrophage and regulatory T-cells from patients with Crohn’s Disease when compared to those not affected. Together, these data suggest that a primary defect in the coordination of the host response to viral infection in the hematopoietic compartment, through nucleic acid sensing and subsequent interferon signaling may be fundamentally linked with the pathogenesis of Crohn’s Disease.

scholarly journals HIV-1 Infection Transcriptomics: Meta-Analysis of CD4+ T Cells Gene Expression Profiles

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 244 ◽  
Author(s):  
Antonio Victor Campos Coelho ◽  
Rossella Gratton ◽  
João Paulo Britto de Melo ◽  
José Leandro Andrade-Santos ◽  
Rafael Lima Guimarães ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Differentially Expressed Genes ◽  
Cd4 T Cells ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Infected Cells ◽  
Hiv 1

HIV-1 infection elicits a complex dynamic of the expression various host genes. High throughput sequencing added an expressive amount of information regarding HIV-1 infections and pathogenesis. RNA sequencing (RNA-Seq) is currently the tool of choice to investigate gene expression in a several range of experimental setting. This study aims at performing a meta-analysis of RNA-Seq expression profiles in samples of HIV-1 infected CD4+ T cells compared to uninfected cells to assess consistently differentially expressed genes in the context of HIV-1 infection. We selected two studies (22 samples: 15 experimentally infected and 7 mock-infected). We found 208 differentially expressed genes in infected cells when compared to uninfected/mock-infected cells. This result had moderate overlap when compared to previous studies of HIV-1 infection transcriptomics, but we identified 64 genes already known to interact with HIV-1 according to the HIV-1 Human Interaction Database. A gene ontology (GO) analysis revealed enrichment of several pathways involved in immune response, cell adhesion, cell migration, inflammation, apoptosis, Wnt, Notch and ERK/MAPK signaling.

scholarly journals AB0108 USING RNA SEQUENCING TO IDENTIFY GENE EXPRESSION SIGNATURES ASSOCIATED WITH RESPONSE TO ABATACEPT IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1082-1083
Author(s):  
H. H. Chen ◽  
W. C. Chao ◽  
J. R. Wang ◽  
T. M. Ko
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Mhc Class Ii ◽  
Whole Blood ◽  
Antigen Processing ◽  
Cytokine Production ◽  
Rna Seq ◽  
Eular Response ◽  
Gene Expression Signatures ◽  
Identify Gene Expression

Background:Rheumatoid arthritis (RA) is a common chronic autoimmune disease. Abatacept (CTLA4-immunoglobulin) is one of the biological disease-modifying antirheumatic drug (bDMARD) for RA patients with indequate response to methotrexate. Recently, Yokoyama-Kokuryo et al. compared gene expression levels between abatacept responders and non-responders in RA patients using a microarray and found that type I IFN score and expression levels of nine genes may be used as a biomarker to predict response to abatacept. However, little study used RNA sequencing (RNA-seq) to identify whole blood gene expression signatures to predict therapeutic response to abatacept.Objectives:The aim of this study is to identify gene expression signatures to predict therapeutic responses to abatacept in RA patients using RNA-seq.Methods:This study is a single-center, prospective study. We used a PAX gene Blood RNA kit to collect whole blood at baseline and 4 weeks after abatacept treatment from RA patients. We also measured DAS28, physician global assessment, HAQ, ESR, CRP at baseline and 12 week to calculate EULAR response at 12 week. Patients with good EULAR response were defined as responders and those with moderate or no EULAR response were defined as non-responders.Results:We finally conducted RNA-seq for whole blood from 7 RA patients initiating abatacept therapy. Of the 7 RA patients, one was non-responder and 6 were responders. We first use DESeq2 to analyze the differentially expressed genes of non-responder and responder before taking the drug. We used hierarchical clustering and PCA to evaluate the overall similarity of the samples, and group the patient data, and find that the nonresponder can be distinguished from responders. Subsequently, we analyzed the differentially expressed genes of the two groups of non-responder and responder patients before taking the drug. Before treatment, we found that 72 genes had a higher expression in the non-responder, and 23 genes had a higher expression level in responders. Figure 1 showed the top 20 DEG Heatmap between the non-responder and responders.Using these two sets of genes for GO analysis, we found that most of the pathways in the non-responder are related to immune response and cytokine production, and most of the pathways in the responders are related to antigen processing and MHC class II.Figure 1.Top 20 DEG Heatmap between non-responder and respondersConclusion:The study showed that most of the pathways in RA patients with no EULAR response to abatacept are related to immune response and cytokine production; while most of the pathways in RA patients with moderate/good response to abatacept are related to antigen processing and MHC class II.References:[1]Yokoyama-Kokuyo W, Yamazaki H, Takeuchi T, et al. Identification of molecules associated with response to abatacept in patients with rheumatoid arthritis. Arthritis Research & Therapy. 2020;22:46.Disclosure of Interests:Hsin-Hua Chen Grant/research support from: This is an investigator-sponsored trial with Bristol-Myers Squibb who provides funding support., Wen-Cheng Chao: None declared, Jing-Rong Wang: None declared, Tai-Ming Ko: None declared

scholarly journals Haplotype-Specific Expression Analysis of MHC Class II Genes in Healthy Individuals and Rheumatoid Arthritis Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Miranda Houtman ◽  
Espen Hesselberg ◽  
Lars Rönnblom ◽  
Lars Klareskog ◽  
Vivianne Malmström ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
T Cells ◽  
Mhc Class Ii ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Class Ii ◽  
Differentially Expressed ◽  
Healthy Individuals ◽  
Hla Dq

HLA-DRB1 alleles have been associated with several autoimmune diseases. For anti-citrullinated protein antibody positive rheumatoid arthritis (RA), HLA-DRB1 shared epitope (SE) alleles are the major genetic risk factors. In order to study the genetic regulation of major histocompatibility complex (MHC) Class II gene expression in immune cells, we investigated transcriptomic profiles of a variety of immune cells from healthy individuals carrying different HLA-DRB1 alleles. Sequencing libraries from peripheral blood mononuclear cells, CD4+ T cells, CD8+ T cells, and CD14+ monocytes of 32 genetically pre-selected healthy female individuals were generated, sequenced and reads were aligned to the standard reference. For the MHC region, reads were mapped to available MHC reference haplotypes and AltHapAlignR was used to estimate gene expression. Using this method, HLA-DRB and HLA-DQ were found to be differentially expressed in different immune cells of healthy individuals as well as in whole blood samples of RA patients carrying HLA-DRB1 SE-positive versus SE-negative alleles. In contrast, no genes outside the MHC region were differentially expressed between individuals carrying HLA-DRB1 SE-positive and SE-negative alleles, thus HLA-DRB1 SE alleles have a strong cis effect on gene expression. Altogether, our findings suggest that immune effects associated with different allelic forms of HLA-DR and HLA-DQ may be associated not only with differences in the structure of these proteins, but also with differences in their expression levels.

Chronic Cutaneous GVHD Does Not Correlate with Frequency and FoxP3 Gene Expression of Regulatory T Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1819-1819
Author(s):  
Peter Haeusermann ◽  
Laura Tabellini ◽  
Mary E. Flowers ◽  
Paul J. Martin ◽  
Paul A. Carpenter ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Regulatory T Cells ◽  
Whole Blood ◽  
Hematologic Malignancy ◽  
Chronic Gvhd ◽  
Immunosuppressive Drugs ◽  
Comparable Amount ◽  
Preliminary Results

Abstract OBJECTIVE: The pathogenesis of chronic GVHD and particularly of its skin involvement is incompletely understood. Regulatory CD4+CD25+ T-cells have been shown to influence acute and chronic GVHD disease and so far heterogeneous results considering the frequency of these cells in chronic GVHD have been published. Additionally, reports indicate that chronic GVHD is associated with reduced expression of FoxP3 of these specific T-cells potentially related to posttransplant thymic insufficiency. These investigations have so far not been conducted in the particular setting of isolated chronic cutaneous GVHD. Our objective therefore was to investigate number, immunophenotype and gene expression of T-cells and particularly of regulatory T-cells in whole blood, CD4-enriched T-cells and regulatory T-cells in these patients. Moreover, as immunosuppressive drugs (calcineurin inhibitors and Rapamycine) have been shown to influence the frequency of regulatory T-cells in vitro, our focus was to specifically study highly selected patients without immunosuppressive medications including cyclosporine, FK-506, Rapamycine, Glucocorticosteroids and MTX and with or without active chronic cutaneous GVHD. METHODS: Since June 2005, 14 patients more than 365 days posttransplant because of hematologic malignancy and 4 normal controls have been investigated in this still ongoing study clinically and by T-cell immunophenotyping (whole blood, CD4+ T cells and regulatory T-cells) and gene expression (FoxP3, Il–10 and TGF-beta) with real time PCR. RESULTS: Of all patients included so far, preliminary results indicate, that patients without GVHD at all and without immunosuppressive drugs as well as patients with isolated chronic cutaneous GVHD and off immunosuppressive drugs have a comparable amount of regulatory T-cells and level of gene expression for FoxP3. Patients within these two highly selected subgroups do not have clinical and/or laboratory evidence for gastrointestinal or liver affection. CONCLUSION: With respect to our preliminary results, active chronic cutaneous GVHD in posttransplant patients after day 365 is not related to a decreased number of regulatory T-cells as well as to a reduced level of FoxP3 expression.

scholarly journals Vitamins D2 and D3 have overlapping but different effects on human gene expression revealed through analysis of blood transcriptomes in a randomised double-blind placebo-controlled food-fortification trial

2020 ◽  
Author(s):  
Louise R. Durrant ◽  
Giselda Bucca ◽  
Andrew Hesketh ◽  
Carla Möller-Levet ◽  
Laura Tripkovic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Human Physiology ◽  
South Asian ◽  
Whole Blood ◽  
Biological Effects ◽  
Controlled Trial ◽  
Vitamin D Supplementation ◽  
Differentially Expressed ◽  
Double Blind

AbstractFor the first time, we report the influence of vitamin D2 and vitamin D3 on genome-wide gene expression in whole blood from healthy women representing two ethnic groups, white European and South Asian. In this randomised placebo-controlled trial, participants were given daily physiological doses (15 μg) of either vitamin D2 or D3 for 12 weeks and changes in the transcriptome were compared relative to the transcriptome at baseline. While there was some overlap in the repertoire of differentially expressed genes after supplementation with each vitamin D source, most changes were specific to either vitamin D3 or vitamin D2, suggesting that each form of the vitamin may have different effects on human physiology. Notably, following vitamin D3 supplementation, the majority of changes in gene expression reflected a down-regulation in the activity of genes, many encoding components of the innate and adaptive immune systems. These are consistent with the emerging concept that vitamin D orchestrates a shift in the immune system towards a more tolerogenic status. The profound differences in gene expression after supplementation with vitamin D2 compared with vitamin D3 warrant a more intensive investigation of the biological effects of the two forms of vitamin D on human physiology.Significance statementsThis study suggests that the influence of vitamins D2 and D3 on human physiology may not be the same, as deduced from differences in gene expression within whole blood.South Asian participants were found to respond differently to vitamin D supplementation at the transcriptome level from white Europeans.The differentially expressed immune pathways identified in this study are consistent with vitamin D orchestrating a more tolerogenic immune status and this could be relevant in the context of the severity of immune response to viral infections such as COVID-19.

Quantification and phenotype of regulatory T cells in rheumatoid arthritis according to Disease Activity Score-28

Autoimmunity ◽  
2009 ◽  
pp. 1-1
Author(s):  
Jose Miguel Sempere-Ortells ◽  
Vicente Perez-Garcia ◽  
Gema Marin-Alberca ◽  
Alejandra Peris-Pertusa ◽  
Jose Miguel Benito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Score

scholarly journals Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proinflammatory cytokines in Th17 cells

2020 ◽  
Vol 117 (48) ◽  
pp. 30639-30648
Author(s):  
Dan Hu ◽  
Emily C. Tjon ◽  
Karin M. Andersson ◽  
Gabriela M. Molica ◽  
Minh C. Pham ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
T Cells ◽  
Transcription Factor ◽  
Proinflammatory Cytokines ◽  
Th17 Cells ◽  
Gene Set Enrichment Analysis ◽  
Aberrant Expression ◽  
Signature Genes ◽  
The Impact

IL-17–producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3−CD45RA−CD4+T (CCR6+T) cells isolated from anti-TNF–treated RA patients classified as responders or nonresponders to therapy. CCR6+T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targetingUSF2in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.

scholarly journals OP0286 PROTEOMICS AND RNA SEQUENCING APPROACHES HIGHLIGHT THE ROLE OF ENDOTHELIAL CELL DYSREGULATION IN IL-1 AND IFN MEDIATED AUTOINFLAMMATORY DISEASES, NOMID AND CANDLE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 178-179
Author(s):  
S. Alehashemi ◽  
M. Garg ◽  
B. Sellers ◽  
A. De Jesus ◽  
A. Biancotto ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Whole Blood ◽  
Cell Activation ◽  
Immune Cell ◽  
Differentially Expressed ◽  
Neutrophilic Dermatosis ◽  
Healthy Controls ◽  
Differentially Expressed Proteins ◽  
Rna Seq ◽  
Before And After

Background:Systemic Autoinflammatory diseases present with sterile inflammation. NOMID (Neonatal-Onset Multisystem Inflammatory Disease) is caused by gain-of-function mutations inNLRP3and excess IL-1 production, presents with fever, neutrophilic dermatosis, aseptic meningitis, hearing loss and eye inflammation; CANDLE (Chronic Atypical Neutrophilic Dermatosis, Lipodystrophy and Elevated Temperature) is caused by loss-of-function mutations in proteasome genes that lead to type-1 interferon signaling, characterized by fever, panniculitis, lipodystrophy, cytopenia, systemic and pulmonary hypertension and basal ganglia calcification. IL-1 blockers are approved for NOMID and JAK-inhibitors show efficacy in CANDLE treatment.Objectives:We used proteomic analysis to compare differentially expressed proteins in active NOMID and CANDLE compared to healthy controls before and after treatment, and whole blood bulk RNA seq to identify the immune cell signatures.Methods:Serum samples from active NOMID (n=12) and CANDLE (n=7) before and after treatment (table 1) and age matched healthy controls (HC) (n=7) were profiled using the SomaLogic platform (n=1125 proteins). Differentially expressed proteins in NOMID and CANDLE were ranked after non-parametric tests for unpaired (NOMIDp<0.05, CANDLE,p<0.1) and paired (p<0.05) analysis and assessed by enriched Gene Ontology pathways and network visualization. Whole blood RNA seq was performed (NOMID=7, CANDLE=7, Controls =5) and RPKM values were used to assess immune cells signatures.Table 1.Patient’s characteristicsNOMIDN=12, Male =6CANDLEN=7, Male =6AgeMedian (range)12 (2, 28)16 (3, 20)Ethnicity%White (Hispanic)80 (20)100 (30)GeneticsNLRP3mutation(2 Somatic, 10 Germline)mutations in proteasome component genes(1 digenic, 6 Homozygous/compound Heterozygous)Before treatmentAfter treatmentBefore treatmentAfter treatmentCRPMedian (range) mg/L52 (16-110)5 (0-23)5 (0-101)1 (0-4)IFN scoremedian (range)0NA328 (211-1135)3 (0-548)Results:Compared to control, 205 proteins (127 upregulated, 78 downregulated) were significantly different at baseline in NOMID, compared to 163 proteins (101 upregulated, and 62 downregulated) in CANDLE. 134 dysregulated proteins (85 upregulated, 49 downregulated) overlapped in NOMID and CANDLE (Figure 1). Pathway analysis identified neutrophil and monocyte chemotaxis signature in both NOMID and CANDLE. NOMID patients had neutrophilia and active neutrophils. CANDLE patients exhibited active neutrophils in whole blood RNA. Endothelial cell activation was the most prominent non-hematopoietic signature and suggest distinct endothelial cell dysregulation in NOMID and CANDLE. In NOMID, the signature included neutrophil transmigration (SELE) endothelial cell motility in response to angiogenesis (HGF, VEGF), while in CANDLE the endothelial signatures included extracellular matrix protein deposition (COL8A) suggesting increased vascular stiffness. CANDLE patients had higher expression of Renin, 4 out of 7 had hypertension, NOMID patients did not have hypertension. Treatment with anakinra and baricitinib normalized 143 and 142 of dysregulated proteins in NOMID and CANDLE respectively.Conclusion:Differentially expressed proteins in NOMID and CANDLE are consistent with innate immune cell activation. Distinct endothelial cell signatures in NOMID and CANDLE may provide mechanistic insight into differences in vascular phenotypes. Treatment with anakinra and Baricitinib in NOMID and CANDLE leaves 30% and 13% of the dysregulated proteins unchanged.Acknowledgments:This work was supported by Intramural Research atNational Institute of Allergy Immunology and Infectious Diseases of National Institutes of Health, Bethesda, Maryland, the Center of Human Immunology and was approved by the IRB.Disclosure of Interests:None declared

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