title: The paradox of high availability and low recognition of soluble HLA-G by LILRB1 receptor in rheumatoid arthritis patients.
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 14 bp 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 14 pb 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.
authors: Laboratório de Imunogenética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Tiago Degani
authors: TD
authors: Veit
authors: Laboratório de Imunogenética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: José Artur Bogo
authors: JA
authors: Chies
authors: Institute for Transfusion Medicine, University Hospital of Essen, Essen, Germany.
authors: Magdalena
authors: M
authors: Switala
authors: Institute for Transfusion Medicine, University Hospital of Essen, Essen, Germany.
authors: Bettina
authors: B
authors: Wagner
authors: Institute for Transfusion Medicine, University Hospital of Essen, Essen, Germany.
authors: Peter A
authors: PA
authors: Horn
authors: Laboratório de Imunogenética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Mauricio
authors: M
authors: Busatto
authors: Serviço de Reumatologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors: Claiton Viegas
authors: CV
authors: Brenol
authors: Serviço de Reumatologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors: João Carlos
authors: JC
authors: Tavares Brenol
authors: Serviço de Reumatologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors: Ricardo
authors: R
authors: Machado Xavier
authors: Institute for Transfusion Medicine, University Hospital of Essen, Essen, Germany.
authors: Vera
authors: V
authors: Rebmann
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology / Q000473:pathology; D005260:Female; D005838:Genotype; D059951:HLA-G Antigens / Q000097:blood* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000276:immunology / Q000473:pathology; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000097:blood* / Q000276:immunology
chemical_list: D015703:Antigens, CD; D059951:HLA-G Antigens; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic