Lin X, etal., Hum Immunol. 2016 Feb;77(2):223-9. doi: 10.1016/j.humimm.2015.12.007. Epub 2015 Dec 31.
BACKGROUND: Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. As a member of FCRLs clusters, Fc receptor-like 3 (FCRL3) has been recognized as a neoteric autoimmune activation factor for RA. The aim of our study is to evaluate the correl
ation between four single-nucleotide polymorphisms (SNPs) on FCRL3 and RA risk in a Chinese Han population. MATERIAL AND METHODS: The hospital-based case-control study included 630 RA patients together with 696 healthy individuals as the control group and all subjects are Chinese ancestry. Four tagging single-nucleotide polymorphisms (tag-SNPs) on FCRL3 were selected and genotyped by TaqMan assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were employed to evaluate the correlations between FCRL3 polymorphisms and RA. A systematic meta-analysis was also carried out based on the present study and previously published studies to further examine the association between FCRL3 variations and RA risk. RESULTS: Significant association was found between -169T/C SNP and RA risk (CC vs. TT, OR=1.62, 95% CI=1.18-2.22; TC/CC vs. TT, OR=1.47, 95% CI=1.18-1.84; C vs. T, OR=1.32, 95% CI=1.12-1.54). Apart from that, mutations of -169T/C was significantly correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) positive status. The meta-analysis also suggested that -169T/C mutation might have positive correlation with risk of RA in the overall population, particularly for Asian. Stratified analysis based on clinical characteristics of RF and ACPA also provided evidence that -169T/C polymorphisms could alter phenotypes of RA. CONCLUSION: The FCRL3 -169T/C variant was significantly linked with an increased RA risk in the Chinese Han population. Moreover, this meta-analysis also provides notion that -169T/C variant could act as a susceptible factor for RA. However, further investigations about the functional impacts of this polymorphism are essential to confirm the above conclusions.
Wysocka M, etal., J Invest Dermatol. 2014 Jan;134(1):229-36. doi: 10.1038/jid.2013.279. Epub 2013 Jun 21.
Sezary syndrome (SS) cells express cell surface molecules also found on normal activated CD4 T cells. In an effort to find a more specific surface marker for malignant SS cells, a microarray analysis of gene expression was performed. Results showed significantly increased levels of mRNA for CD164, a
sialomucin found on human CD34+ hematopoietic stem cells, and FCRL3, a molecule present on a subset of human natural T regulatory cells. Both markers were increased in CD4 T cells from SS patients compared with healthy donors (HD). Flow cytometry studies confirmed the increased expression of CD164 and FCRL3 primarily on CD4+CD26- T cells of SS patients. Importantly, a statistically significant correlation was found between an elevated percentage of CD4+CD164+ T cells and an elevated percentage of CD4+CD26- T cells in all tested SS patients but not in patients with mycosis fungoides and atopic dermatitis or HD. FCRL3 expression was significantly increased only in patients with high tumor burden. CD4+CD164+ cells displayed cerebriform morphology and their loss correlated with clinical improvement in treated patients. Our results suggest that CD164 can serve as a marker for diagnosis and for monitoring progression of cutaneous T-cell lymphoma (CTCL)/SS and that FCRL3 expression correlates with a high circulating tumor burden.
Rheumatoid arthritis (RA) is a multifactorial disease. A combination of genetic and environmental risk factors contributes to its etiology. Several genes have been reported to be associated with susceptibility to the development of RA. The MHC2TA and FCRL3 genes
have been associated previously with RA in Swedish and Japanese populations, respectively. In two recent reports, we show an association between FCRL3 and juvenile rheumatoid arthritis (JRA), and MHC2TA and acute coronary syndrome (ACS) in Mexican population. We assessed the association between three single nucleotide polymorphisms (SNPs) of the MHC2TA (-168G/A; rs3087456, and +16G/C; rs4774) and FCRL3 (-169T/C; rs7528684) genes and rheumatoid arthritis in Mexican population through a genotyping method using allelic discrimination assays with TaqMan probes. Our case-control study included 249 patients with RA and 314 controls. We found no evidence of an association between the MHC2TA -168G/A and +1614G/C or FCRL3 -169T/C polymorphisms and RA in this Mexican population. In this cohort of Mexican patients with RA, we observed no association between the MHC2TA or FCRL3 genes and this autoimmune disease.
Multiple sclerosis (MS) is an autoimmune/inflammatory neurodegenerative disease which mainly affects the central nervous system in young adults. Fc-receptor-like-3 (FCRL3) gene, which involved in immune cell regulation, has drawn lots of attentions. This study a
ims to investigate the association between common polymorphisms of FCRL3 gene and MS risk in a Chinese Han population. Nine single nucleotide polymorphisms (SNPs) were genotyped in 120 patients and 240 healthy controls through PCR assay. t test and chi-square test was conducted to find a possible association between FCRL3 genetic mutations and risk of MS. This analysis results performed that four SNPs, rs7528684 (FCRL3_3), rs945635 (FCRL3_5), rs3761959 (FCRL3_6), and rs2282284 (FCRL3_8), were significantly associated with the risk of MS. Further haplotype analysis showed two haplotypes of FCRL3_3, 5, 6, 8, CCAG and CGAG, presented the significant associations with the susceptibility to MS. Four SNPs in FCRL3 gene could possibly associate with the susceptibility of MS in a Chinese Han population. Moreover, the haplotype analysis confirmed that the linkage disequilibrium exists in polymorphisms in FCRL3. Based on the supporting evidence, we deduced that FCRL3_3C, FCRL3_5C, FCRL3_6A, and FCRL3_8G caused increased risk of MS. Nevertheless, large cohort studies are required in the future to validate the autoimmune function.
Wojciechowska-Durczynska K, etal., Neuro Endocrinol Lett. 2016;37(1):65-9.
BACKGROUND: Numerous genetic studies revealed several susceptibility genes of autoimmune thyroid diseases (AITD), including CTLA4, PTPN22 and FCRL3. These immune-modulating genes are involved in genetic background of AITD among children and adult patients. Howev
er, possible age-related differences in overexpression of these genes remain unclear. PURPOSE: The goal of this single centre cohort study was evaluation of expression levels of three (3) genes CTLA4, PTPN22 and FCRL3 in adult patients and children with autoimmune thyroiditis. METHODS: A total of 47 patients--24 adults (mean age--47.7 years) and 23 children (mean age--12.4 years) with autoimmune thyroiditis were assessed for the level of expression of CTLA4, PTPN22 and FCRL3 genes, utilizing ABI PRISM' 7500 Sequence Detection System (Applied Biosystem, Foster City, CA, USA). RESULTS: The overexpression of PTPN22 (mean RQ = 2.988) and FCRL3 (mean RQ = 2.544) genes were confirmed in adult patients with autoimmune thyroiditis, at the same time the expression level of CTLA4 gene was significantly decreased (mean RQ = 0.899) (p < 0.05). Similar discrepancies were not observed in children with autoimmune thyroiditis in whom overexpression of all three genes--CTLA4, PTPN22 and FCRL3--was observed. Differences in CTLA4 and FCRL3 genes expression levels in patients with autoimmune thyroiditis were found depending on the age, with increased expression levels of CTLA4 (mean RQ = 3.45 1) and FCRL3 (mean RQ = 7.410) in children when compared to adults (p < 0.05) (Mann-Whitney's U-test). There were moderate negative linear correlations between two genes in question (CTLA4 and FCRL3) expression level and patients' age [correlation coefficient (r) = -0.529 (p < 0.0002) and -0.423 (p < 0.0032), respectively; Spearman's rank correlation test]. CONCLUSION: Our results are consistent with the hypothesis that there are few age-dependent genetic differences as regards autoimmune thyroiditis in adults and children. Accordingly, CTLA4 and FCRL3 genes overexpression may play an important role in children suffering from autoimmune thyroiditis.
Takata Y, etal., J Hum Genet. 2008;53(2):163-73. Epub 2007 Dec 18.
We conducted population-based association tests for the four selected SNPs (rs2240340/padi4_94, rs7528684/fcrl3_3, rs3792876/slc2F2 and rs2268277/runx1) previously reported to be associated with rheumatoid arthritis (RA). The study population consisted of 950 un
related Japanese subjects with RA and 507 controls, none of whom had previously been tested for these variants. Only the SNP rs2240340/padi4_94 was modestly associated with RA [allele odds ratio (OR) 1.22, 95% confidence interval (CI) 1.04-1.43, P=0.012]. The most significant association effect was found for genotype contrast between minor and major allele homozygotes (OR 1.53, 95% CI 1.10-2.12, P=0.010). No other SNPs showed a statistically significant association with RA in our population. Meta-analysis of published studies and our new data confirmed a highly significant association between PADI4 gene SNPs and increased risk of RA in East Asian populations (allele fixed-effects summary OR 1.31, 95% CI 1.22-1.41, P<0.0001). We found some evidence for an association of either rs7528684/fcrl3_3 or rs3792876/slc2F2 with RA; however, because the magnitudes of effects were apparently much weaker than those reported in the initial positive reports, and there were substantial levels of inter-study OR heterogeneity, we concluded that additional studies are needed to fully understand the present results.
