The Paradox of High Availability and Low Recognition of Soluble HLA-G by LILRB1 Receptor in Rheumatoid Arthritis Patients |
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Authors: | Tiago Degani Veit José Artur Bogo Chies Magdalena Switala Bettina Wagner Peter A Horn Mauricio Busatto Claiton Viegas Brenol Jo?o Carlos Tavares Brenol Ricardo Machado Xavier Vera Rebmann |
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Institution: | 1. Laboratório de Imunogenética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.; 2. Institute for Transfusion Medicine, University Hospital of Essen, Essen, Germany.; 3. Serviço de Reumatologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.; University of London, St George''s, UNITED KINGDOM, |
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Abstract: | HLA-G is a regulatory molecule involved in immunologic tolerance. Growing evidence indicates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. This study aimed at a systematic evaluation of soluble HLA-G (sHLA-G) in plasma of rheumatoid arthritis (RA) patients with long-lasting chronic inflammation. RA patients (n=68) and healthy controls (n=26) had their plasmatic sHLA-G measured by ELISA whereas the binding capability of sHLA-G to its cognate LILRB1 receptor was measured by a Luminex-based assay. All subjects were PCR-genotyped for HLA-G 14bp polymorphism (rs66554220). Significantly higher sHLA-G levels were observed in patients (p<0.001), however no significant differences were observed in LILRB1 binding capacity between RA patients and controls. Remarkably, the proportion of patients presenting specific binding of sHLA-G to LILRB1 was significantly decreased as compared to controls (56% vs. 81%, p=0.027). Patients without rheumatoid factor (RF-) were significantly overrepresented in the group of patients positive for LILRB1 binding as compared to patients without LILRB1 binding (31% vs 10%, p=0.033). Furthermore, methotrexate treated patients (n=58) revealed significantly lower LILRB1 binding to sHLA-G molecules than non-treated patients (medians: 12.2 vs. 67.7 units/ml, p=0.031). Unlike in controls, no significant differences in sHLA-G levels were observed among patients grouped by 14pb genotype. Thus, in a substantial number of late RA patients, the circulating sHLA-G molecules are impaired regarding LILRB1 recognition, meaning that although increased levels are observed; these molecules are not qualified to exert their protective functions against inflammation. Our findings offer new insights into the immunopathology of RA patients with long-lasting anti-RA-treatment and highlight the importance to also measure the binding capability of sHLA-G to LILRB1. |
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