Dataset Information

Efficacy of abatacept for arthritis in patients with an overlap syndrome between rheumatoid arthritis and systemic lupus erythematosus.

ABSTRACT:

Introduction

This study aimed to investigate the efficacy of abatacept for arthritis in patients with rhupus, an overlap syndrome between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

Methods

Patients who fulfilled both the 2010 ACR/EULAR criteria for RA classification and the 1997 ACR revised criteria for classification of SLE and received abatacept treatment for arthritis were retrospectively studied.

Results

Six rhupus patients who fulfilled the inclusion criteria above were identified. All patients had active arthritis despite receiving antirheumatic drugs including methotrexate when abatacept was initiated. Clinical Disease Activity Index (CDAI) significantly decreased between baseline and 12 weeks (P = 0.028) and remained low through 24 weeks. All patients achieved either a good or moderate response according to the EULAR response criteria at 24 weeks. Health Assessment Questionnaire-Disability Index (HAQ-DI) also significantly decreased between baseline and 24 weeks (P = 0.043). In addition, the levels of immunoglobulin G and anti-DNA antibody significantly decreased between baseline and 24 weeks (P = 0.028 and P = 0.043, resp.).

Conclusions

Treatment with abatacept is likely to be efficacious in patients with rhupus whose arthritis is refractory to methotrexate. In addition, abatacept may have a moderate effect on abnormal antibody production in rhupus patients.

SUBMITTER: Ikeda K

PROVIDER: S-EPMC3845485 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Efficacy of abatacept for arthritis in patients with an overlap syndrome between rheumatoid arthritis and systemic lupus erythematosus.

Ikeda Kei K Sanayama Yoshie Y Makita Sohei S Hosokawa Junichi J Yamagata Mieko M Nakagomi Daiki D Takabayashi Katsuhiko K Nakajima Hiroshi H

Clinical & developmental immunology 20131114

<h4>Introduction</h4>This study aimed to investigate the efficacy of abatacept for arthritis in patients with rhupus, an overlap syndrome between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).<h4>Methods</h4>Patients who fulfilled both the 2010 ACR/EULAR criteria for RA classification and the 1997 ACR revised criteria for classification of SLE and received abatacept treatment for arthritis were retrospectively studied.<h4>Results</h4>Six rhupus patients who fulfilled the inclu ...[more]

PMID: 24324510

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Project description:BackgroundClinical and epidemiological studies have suggested systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are comorbidities and common genetic etiologies can partly explain such coexistence. However, shared genetic determinations underlying the two diseases remain largely unknown.MethodsOur analysis relied on summary statistics available from genome-wide association studies of SLE (N = 23,210) and RA (N = 58,284). We first evaluated the genetic correlation between RA and SLE through the linkage disequilibrium score regression (LDSC). Then, we performed a multiple-tissue eQTL (expression quantitative trait loci) weighted integrative analysis for each of the two diseases and aggregated association evidence across these tissues via the recently proposed harmonic mean P-value (HMP) combination strategy, which can produce a single well-calibrated P-value for correlated test statistics. Afterwards, we conducted the pleiotropy-informed association using conjunction conditional FDR (ccFDR) to identify potential pleiotropic genes associated with both RA and SLE.ResultsWe found there existed a significant positive genetic correlation (r g = 0.404, P = 6.01E-10) via LDSC between RA and SLE. Based on the multiple-tissue eQTL weighted integrative analysis and the HMP combination across various tissues, we discovered 14 potential pleiotropic genes by ccFDR, among which four were likely newly novel genes (i.e., INPP5B, OR5K2, RP11-2C24.5, and CTD-3105H18.4). The SNP effect sizes of these pleiotropic genes were typically positively dependent, with an average correlation of 0.579. Functionally, these genes were implicated in multiple auto-immune relevant pathways such as inositol phosphate metabolic process, membrane and glucagon signaling pathway.ConclusionThis study reveals common genetic components between RA and SLE and provides candidate associated loci for understanding of molecular mechanism underlying the comorbidity of the two diseases.

Project description:BackgroundRheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q.MethodsWe tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus.ResultsA SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P=2.81x10(-7); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P=0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P=1.87x10(-9); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis.ConclusionsA haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses.

Project description:BackgroundSjögren's syndrome (SS) shares many clinical and pathological similarities with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). These autoimmune diseases mostly affect women. In this study, concept profile analysis (CPA) and gene expression meta-analysis were used to identify genes potentially involved in SS pathogenesis.MethodsHuman genes associated with SS, SLE, and RA were identified using the CPA tool, Anni 2.1. The differential mRNA expression of genes common to SS and SLE (SS-SLE) was determined in female peripheral blood mononuclear cells (PBMCs) using NCBI-GEO2R. Differentially expressed (DE) SS-SLE PBMC genes in common with the SS-SLE CPA-identified genes were analyzed for differential expression in salivary glands or synovial biopsies, and for genes common to SS and RA and SLE and RA, analyzing differential expression in salivary glands in SS, synovial fibroblasts in RA, and synovial fluid in SLE. Among common genes, DE genes found in salivary gland mRNA expression in patients with SS were used for gene enrichment and SS molecular network construction. Secondary analysis was performed to identify DE genes unique to the disease site tissues, by excluding PBMC and CPA common DE genes to complement the SS network.ResultsWe identified 22 DE genes in salivary gland datasets in SS that have not previously been clearly associated with SS pathogenesis. Among these, higher levels of checkpoint kinase 1 (CHEK1), V-Ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS1), and lymphoid enhancer binding factor 1 (LEF1) were significantly correlated with higher matrix metalloproteinase 9 (MMP9) levels. Higher MMP9 levels have been implicated in degradation of salivary gland structural integrity, leading to hypo-salivation in patients with SS. Salivary gland mRNA expression of MMP9 and the expression of cytokine CXCL10 were higher in patients with SS. CXCL10 has been shown to increase MMP9 expression and therefore may also play an important role in SS pathogenesis.ConclusionUsing CPA and gene expression analysis, we identified factors targeting MMP9 expression and/or function, namely CHEK1, CXCL10, ETS1, LEF1, and tissue inhibitor of metalloproteinase 1; altered mRNA expression of these could increase expression/activity of MMP9 in a concerted manner, thereby potentially impacting SS pathogenesis.

Dataset Information

Efficacy of abatacept for arthritis in patients with an overlap syndrome between rheumatoid arthritis and systemic lupus erythematosus.

Introduction

Methods

Results

Conclusions

Publications

Efficacy of abatacept for arthritis in patients with an overlap syndrome between rheumatoid arthritis and systemic lupus erythematosus.

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