Macrophage-inducible C-type lectin is associated with anti-cyclic citrullinated peptide antibodies-positive rheumatoid arthritis in men / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Macrophage-inducible C-type lectin (MINCLE) is an important member of C-type lectin superfamily, which has been shown evidence for susceptibility to arthritis in animal models. We aimed to investigate the possible association of MINCLE with rheumatoid arthritis (RA) susceptibility in Chinese Han population.</p><p><b>METHODS</b>Haplotypes from HapMap database (Chinese Han Beijing, CHB) were used to select tag-single nucleotide polymorphism (SNP) (r(2) = 0.8) residing in MINCLE gene. A total of 563 patients with RA and 404 healthy controls were TagMan genotyped for SNP rs10841845. Association analyses were performed on the whole data set and on RA subsets based on gender difference and the status of anti-cyclic citrullinated peptide (anti-CCP) antibody in RA patients. Association statistics were calculated by age and sex adjusted logistic regression.</p><p><b>RESULTS</b>Overall, MINCLE SNP rs10841845 was not associated with susceptibility to RA. However, following anti-CCP stratification, rs10841845 GG genotypes conferred a significantly protective effects against anti-CCP-positive RA (OR 0.65, 95%CI 0.430 - 0.995, P = 0.048). Following gender stratification, SNP rs10841845 G allele appeared to insert its RA protective effect only in male patients, both at allele level (G vs. A OR 0.66, 95%CI 0.46 - 0.93, P = 0.018) and at genotype level (GG vs. AA+AG, OR 0.429, 95%CI 0.20 - 0.95, P = 0.036). Notably, the male RA protective effect of rs10841845 G allele was only seen in anti-CCP-positive RA (G vs. A: OR 0.64, 95%CI 0.43 - 0.96, P = 0.029; GG vs. AA+AG: OR 0.375, 95%CI 0.14 - 0.94, P = 0.038). Furthermore, we observed a significant reduction of Disease Activity Score (DAS) 28 score (3.91 ± 0.70 vs. 5.66 ± 0.31, P = 0.022) and serum C-reactive protein levels (31.64 ± 24.13 vs. 91.80 ± 12.02, P = 0.012) in male anti-CCP-positive RA patients carrying rs10841845 GG genotype, compared with patients carrying AA+AG genotypes.</p><p><b>CONCLUSIONS</b>Our study provides the evidence for a gender specific association between MINCLE rs10841845 and RA susceptibility. The SNP rs10841845 G allele appears to have protective effect against anti-CCP-positive RA and confer reduced RA activity in men.</p>

Serum IgA against type 3 muscarinic acetylcholine receptor is a novel marker in diagnosis of Sjögren's syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Antibodies against type 3 muscarinic acetylcholine receptor (M3R) are involved in the pathogenesis of Sjögren's syndrome (SS), but the clinical value of them in SS patients has been controversial. The aims of this study were to: (1) establish an improved enzyme-linked immunosorbent assay (ELISA) to detect IgA antibodies against M3R; (2) evaluate the value of IgA antibodies against the second extracellular loop of M3R205-220 (c2M3RP) in diagnosis of SS.</p><p><b>METHODS</b>To increase the ELISA sensitivity, c2M3RP was coupled to bovine serum albumin (BSA) by the glutaraldehyde method and a 96-well microplate was treated by ultraviolet rays before coated. Concentrations of anti-c2M3RP, anti-SSA, and anti-SSB were measured in the sera of 240 individuals: 91 patients with primary SS and 149 controls (16 secondary SS, 27 systemic lupus erythematosus, 40 rheumatoid arthritis and 66 healthy controls). Diagnostic properties of anti-c2M3RP were determined by receiver-operating characteristic curve analysis.</p><p><b>RESULTS</b>The prevalence of serum IgA anti-c2M3RP antibodies in patients with pSS (46%, 42/91) was significantly higher than that in patients with systemic lupus erythematosus (19%, 5/27), in rheumatoid arthritis (15%, 6/40) and in healthy controls (5%, 3/66). However, there was no significant difference between the two SS groups (P = 0.727). The diagnostic performance of IgA anti-M3RP antibodies was similar to anti-SSA assay, but had 22% higher sensitivity than anti-SSB. By analyzing of IgA anti-c2M3RP antibodies, combination of anti-SSA and anti-SSB resulted in increased sensitivity, whereas their specificity was not significantly changed.</p><p><b>CONCLUSIONS</b>The improved anti-c2M3RP ELISA is a novel, sensitive, and specific serological test for the diagnosis of SS. The combined application of anti-c2M3RP, anti-SSA and anti-SSB tests can improve the laboratory diagnosis of SS. The IgA anti-c2M3RP antibodies may serve as a novel diagnostic marker for SS.</p>