Dense Genotyping of Immune-Related Regions Identifies Loci for Rheumatoid Arthritis Risk and Damage in African Americans.

Over 100 risk loci for rheumatoid arthritis (RA) have been identified in individuals of European and Asian descent, but the genetic basis for RA in African Americans is less well understood. We genotyped 610 African Americans with autoantibody positive RA and 933 African American controls on the ImmunoChip (iChip) array. Using multivariable regression we evaluated the association between iChip markers and the risk of RA and radiographic severity.

Increased pretreatment serum IFN-β/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis.

Objective: Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement.

Methods: We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry.

The Genotype and Phenotype (GaP) registry: a living biobank for the analysis of quantitative traits.

We describe the development of the Genotype and Phenotype (GaP) Registry, a living biobank of normal volunteers who are genotyped for genetic markers related to human disease. Participants in the GaP can be recalled for hypothesis driven study of disease associated genetic variants. The GaP has facilitated functional studies of several autoimmune disease associated loci including Csk, Blk, PDRM1 (Blimp-1) and PTPN22.

Modular analysis of peripheral blood gene expression in rheumatoid arthritis captures reproducible gene expression changes in tumor necrosis factor responders.

Objective: To establish whether the analysis of whole-blood gene expression is useful in predicting or monitoring response to anti-tumor necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA).

Methods: Whole-blood RNA (using a PAXgene system to stabilize whole-blood RNA in the collection tube) was obtained at baseline and at 14 weeks from 3 independent cohorts, consisting of a combined total of 240 RA patients who were beginning therapy with anti-TNF. We used an approach to gene expression analysis that is based on modular patterns of gene expression, or modules.

Identification of a genetic variant for joint damage progression in autoantibody-positive rheumatoid arthritis.

Background: Joint destruction is a hallmark of autoantibody-positive rheumatoid arthritis (RA), though the severity is highly variable between patients. The processes underlying these interindividual differences are incompletely understood.

Methods: We performed a genome-wide association study on the radiological progression rate in 384 autoantibody-positive patients with RA.

Beliefs and attitudes towards participating in genetic research - a population based cross-sectional study.

Background: Biobanks have the potential to offer a venue for chronic disease biomarker discovery, which would allow for disease early detection and for identification of carriers of a certain predictor biomarker. To assess the general attitudes towards genetic research and participation in biobanks in the Long Island/Queens area of New York, and what factors would predict a positive view of such research, participants from the NSLIJ hospital system were surveyed.

Methods: Participants were recruited at six hospital centers in the NSLIJ system during the summers of 2009 and again in 2011 (n = 1,041).

Gene expression patterns in peripheral blood cells associated with radiographic severity in African Americans with early rheumatoid arthritis.

Gene expression profiling may be used to stratify patients by disease severity to test the hypothesis that variable disease outcome has a genetic component. In order to define unique expression signatures in African American rheumatoid arthritis (RA) patients with severe erosive disease, we undertook a gene expression study using samples of RNA from peripheral blood mononuclear cells (PBMCs). RNA from baseline PBMC samples of 96 African American RA patients with early RA (<2 years disease duration) was hybridized to cDNA probes of the Illumina Human HT-V3 expression array.

Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy.

Objective: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy.

Methods: A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts.

Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction in rheumatoid arthritis.

Objective: The severity of joint destruction in rheumatoid arthritis (RA) is highly variable from patient to patient and is influenced by genetic factors. Genome-wide association studies have enormously boosted the field of the genetics of RA susceptibility, but risk loci for RA severity remain poorly defined. A recent meta-analysis of genome-wide association studies identified 6 genetic regions for susceptibility to autoantibody-positive RA: CD40, KIF5A/PIP4K2C, CDK6, CCL21, PRKCQ, and MMEL1/TNFRSF14.

Genome-wide association scan identifies candidate polymorphisms associated with differential response to anti-TNF treatment in rheumatoid arthritis.

The prediction of response (or non-response) to anti-TNF treatment for rheumatoid arthritis (RA) is a pressing clinical problem. We conducted a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning anti-TNF therapy as part of Autoimmune Biomarkers Collaborative Network (ABCoN [Autoimmune Bio-markers Collaborative Network]) patient cohort. Response to therapy was determined by the change in Disease Activity Score (DAS28) observed after 14 wks.

Interaction between smoking, the shared epitope, and anti-cyclic citrullinated peptide: a mixed picture in three large North American rheumatoid arthritis cohorts.

Objective: Recently, Swedish members of the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) provided evidence that smoking may trigger RA-specific immune reactions to citrullinated protein in carriers of HLA-DR shared epitope alleles. In an effort to confirm this interaction between smoking and shared epitope alleles, we performed a case-only analysis of 3 North American RA cohorts.

Methods: A total of 2,476 white patients with RA were studied, 1,105 from the North American Rheumatoid Arthritis Consortium (NARAC) family collection, 753 from the National Inception Cohort of Rheumatoid Arthritis Patients (Inception Cohort), and 618 from the Study of New Onset Rheumatoid Arthritis (SONORA).

Microarray analyses of peripheral blood cells identifies unique gene expression signature in psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic and erosive form of arthritis of unknown cause. We aimed to characterize the PsA phenotype using gene expression profiling and comparing it with healthy control subjects and patients rheumatoid arthritis (RA). Peripheral blood cells (PBCs) of 19 patients with active PsA and 19 age- and sex-matched control subjects were used in the analyses of PsA, with blood samples collected in PaxGene tubes.

Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: contrasting effects of HLA-DR3 and the shared epitope alleles.

Objective: To examine the association between HLA-DRB1 alleles and the production of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) autoantibodies in patients with rheumatoid arthritis (RA).

Methods: We studied 1,723 Caucasian RA patients enrolled in the North American Rheumatoid Arthritis Consortium (NARAC) family cohort and the Study of New Onset Rheumatoid Arthritis (SONORA) cohort. All patients were tested for anti-CCP antibodies (by enzyme-linked immunosorbent assay), RF (by nephelometry), and HLA-DR genotype (by polymerase chain reaction and sequence-specific oligonucleotide hybridization).

Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes.

Autoimmune disorders constitute a diverse group of phenotypes with overlapping features and a tendency toward familial aggregation. It is likely that common underlying genes are involved in these disorders. Until very recently, no specific alleles--aside from a few common human leukocyte antigen class II genes--had been identified that clearly associate with multiple different autoimmune diseases.