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Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

The objective of this study was to determine the relationship between citrullinated proteins in synovial tissue with peripheral anti-citrullinated peptides autoantibodies (ACPA) and peptidylarginine deiminase (PADI) PADI2, PADI3, and PADI4 messenger RNA (mRNA) expressions in synovial tissue and fibroblast-like synoviocytes in rheumatoid arthritis (RA) patients. Eleven RA and 12 osteoarthritis (OA) patients who underwent knee replacement surgery were studied. We detected citrullinated proteins in synovial tissue homogenates by western blot and serum ACPA by ELISA to anti-cyclic citrullinated peptide (anti-CCP) antibodies, and PADI2, PADI3, and PADI4 mRNA expressions in synovial tissue and in fibroblast-like synoviocytes. Patients with high amount of citrullinated proteins in synovial tissue (3 out of 7) have high levels of anti-CCP in serum. However, in the remaining 4 patients, the amount of synovial citrullinated proteins was minimal and their sera showed low levels of anti-CCP antibodies. Furthermore, we observed an increase in PADI2 mRNA expression in RA synovial tissue compared with OA patients (p = 0.02). We detected PADI3 mRNA in the synovial tissue of RA patients, but not in the tissue of OA patients. Even though fibroblast-type synoviocytes in RA are not the main source of PADs in the synovial tissue, they express PADI2 mRNA moderately, PADI4 mRNA weakly, while there is no detectable expression of PADI3 mRNA. In conclusion, we found a variety of citrullinated proteins in the synovial tissue of RA patients and the amount of such proteins is related to serum concentration of anti-CCP antibodies. We identified the presence of PADI3 mRNA expression in synovial tissue and PADI2 and PADI4 mRNA expressions in fibroblast-like synoviocytes from patients with RA.

Introduction: Human leukocyte antigen (HLA) polymorphism studies in Systemic Sclerosis (SSc) have yielded variable results. These studies need to consider the genetic admixture of the studied population. Here we used our previously reported definition of genetic admixture of Mexicans using HLA class I and II DNA blocks to map genetic susceptibility to develop SSc and its complications., Methods: We included 159 patients from a cohort of Mexican Mestizo SSc patients. We performed clinical evaluation, obtained SSc-associated antibodies, and determined HLA class I and class II alleles using sequence-based, high-resolution techniques to evaluate the contribution of these genes to SSc susceptibility, their correlation with the clinical and autoantibody profile and the prevalence of Amerindian, Caucasian and African alleles, blocks and haplotypes in this population., Results: Our study revealed that class I block HLA-C*12:03-B*18:01 was important to map susceptibility to diffuse cutaneous (dc) SSc, HLA-C*07:01-B*08:01 block to map the susceptibility role of HLA-B*08:01 to develop SSc, and the C*07:02-B*39:05 and C*07:02-B*39:06 blocks to map the protective role of C*07:02 in SSc. We also confirmed previous associations of HLA-DRB1*11:04 and -DRB1*01 to susceptibility to develop SSc. Importantly, we mapped the protective role of DQB1*03:01 using three Amerindian blocks. We also found a significant association for the presence of anti-Topoisomerase I antibody with HLA-DQB1*04:02, present in an Amerindian block (DRB1*08:02-DQB1*04:02), and we found several alleles associated to internal organ damage. The admixture estimations revealed a lower proportion of the Amerindian genetic component among SSc patients., Conclusion: This is the first report of the diversity of HLA class I and II alleles and haplotypes Mexican patients with SSc. Our findings suggest that HLA class I and class II genes contribute to the protection and susceptibility to develop SSc and its different clinical presentations as well as different autoantibody profiles in Mexicans.

Rheumatoid arthritis is an autoimmune disease of multifactorial etiology characterized by inflammation of the joints and presence of autoantibodies directed against multiple autoantigens. Recently the study of the anti-citrullinated protein antibodies (ACP) has acquired great interest due to its high specificity and sensitivity for diagnosis, in addition to which it has shown to be a predictor of severity in patients with rheumatoid arthritis, suggesting an important participation in the pathogenesis of the disease., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

• Anti-lymphocyte autoantibodies (ALA) may contribute to inhibition of the HIV Env-mediated lymphocyte membrane fusion. • IgG and IgM binding to Jurkat CD4-negative cells was detected in most of HIV+ sera. • Absorption on CD4-negative Jurkat cells reduced the fusion inhibition activity of 58% of sera. • Detection of fusion inhibitory ALA, but not total ALA levels, associated with low plasma viral loads. • Specific ALA may participate in virus containment in many HIV+ patients. The HIV-1 envelope protein (Env) mediates the membrane fusion process allowing virus entry to target cells and the efficiency to induce membrane fusion is an important determinant of HIV-1 pathogenicity. In addition to virus receptors, other adhesion/signaling molecules on infected and target cells and virus particles can enhance fusion. The presence of antilymphocyte autoantibodies (ALA) in HIV patients' serum suggests that they may contribute to the inhibition of Env-mediated membrane fusion. Here, sera from 38 HIV-1 infected treatment-naïve men and 30 healthy donors were analyzed for the presence of IgG and IgM able to bind to CD4-negative Jurkat cells. The use of CD4-negative cells precluded the binding of virus-antibody immune complexes, and allowed detection of ALA different from anti-CD4 antibodies. IgG and IgM antibodies binding to Jurkat CD4-negative cells was detected in 74% and 84% of HIV-positive sera, respectively. Then, the activity of sera on fusion of CD4+ with HIV Env+ Jurkat cells was determined before and after their adsorption on CD4-negative Jurkat cells to remove ALA. Sera inhibited fusion at variable extents, and inhibitory activity decreased in 58% of serum samples after adsorption, indicating that ALA contributed to fusion inhibition in these sera (herein called fusion inhibitory ALA). The contribution of ALA to fusion inhibition in individual sera was highly variable, with an average of 33%. IgG purified from a pool of HIV+ sera inhibited fusion of primary CD4 T lymphocytes with Jurkat Env+, and adsorption of IgG on CD4-negative Jurkat cells diminished the fusion inhibitory activity. Thus, the inhibitory activity of sera was related to IgG ALA. Our observations suggest that fusion inhibitory ALA other than anti-CD4 antibodies may contribute significantly to the inhibition of Env-mediated cell-cell fusion. Fusion inhibitory ALA, but not total ALA levels, associated with low plasma viral loads, suggesting that specific ALA may participate in virus containment by inhibiting virus-cell fusion in a significant fraction of HIV-infected patients. [ABSTRACT FROM AUTHOR]