A functional variant in FCRL3 is associated with higher Fc receptor-like 3 expression on T cell subsets and rheumatoid arthritis disease activity

University of California, San Francisco, CA 94110, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 08/2012; 64(8):2451-9. DOI: 10.1002/art.34457
Source: PubMed


CD4+FoxP3+ Treg cells suppress effector T cells and prevent autoimmune disease. Treg cell function is deficient in active rheumatoid arthritis (RA), a loss which may play a role in the pathogenesis of this disease. We previously showed that a single-nucleotide polymorphism in the FCRL3 gene led to higher expression of Fc receptor-like 3 (FcRL3) on Treg cells and that FcRL3+ Treg cells are functionally deficient in comparison to FcRL3- Treg cells. This study was undertaken to investigate the potential role of FcRL3 in RA.
A cross-sectional study was performed to evaluate the FCRL3 -169 genotype and FcRL3 expression on T cell subsets, including Treg cells, in peripheral blood samples from 51 patients with RA enrolled in the University of California, San Francisco (UCSF) RA Cohort. Clinical data were obtained from the UCSF RA Cohort database.
Patients with the FCRL3 -169C allele (genotype C/C or C/T) expressed higher levels of FcRL3 on Treg cells, and on CD8+ and γ/δ T cells, in comparison to RA patients with the T/T genotype. Higher FcRL3 expression on these T cell subpopulations correlated with RA disease activity in patients harboring the FCRL3 -169C allele. Furthermore, FcRL3 expression on Treg cells was higher in patients with erosive RA, and the FCRL3 -169C allele was overrepresented in patients with erosive RA.
Our findings indicate that FcRL3 expression, which is strongly associated with the presence of the FCRL3 -169C allele, may serve as a biomarker for RA disease activity.

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Available from: Jeff E Mold, Oct 27, 2015
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    • "The extracellular ligands as well as functions of these receptors are still unknown or controversial [33], [34], [35], [36]. However, several genetic studies also revealed FCRL gene variants were associated with multiple immune-related diseases, no matter in genome-wide association studies or in candidate gene based studies [37], [38], [39], [40], [41]. All the above highlighted the central bridging roles of FcγRs and FcRLs in immunity with their genetic variants to make up a sort of susceptibility background. "
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