On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis
| Autor: | Anders Lundquist, Heidi Kokkonen, Manfred Wuhrer, René E. M. Toes, Lise Hafkenscheid, Solbritt Rantapää-Dahlqvist, Theresa Kissel, Karin Anna van Schie, Hans Scherer, Tom W J Huizinga |
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| Přispěvatelé: | Graduate School, AII - Inflammatory diseases |
| Jazyk: | angličtina |
| Předmět: |
musculoskeletal diseases
Glycan Glycosylation Immunology Somatic hypermutation Human leukocyte antigen Anti-Citrullinated Protein Antibodies General Biochemistry Genetics and Molecular Biology Arthritis Rheumatoid Epitopes 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Rheumatology immune system diseases medicine Humans Immunology and Allergy Allele skin and connective tissue diseases Alleles Chromatography High Pressure Liquid 030304 developmental biology 030203 arthritis & rheumatology 0303 health sciences HLA-A Antigens biology Transition (genetics) business.industry medicine.disease carbohydrates (lipids) chemistry Immunoglobulin G Rheumatoid arthritis Disease Progression biology.protein Antibody business Follow-Up Studies Forecasting |
| Zdroj: | Annals of the rheumatic diseases, 78(12), 1616-1620. BMJ Publishing Group Annals of the Rheumatic Diseases, 78(12), 1616-1620 Annals of the Rheumatic Diseases Annals of the Rheumatic Diseases, 78(12), 1616-1620. BMJ PUBLISHING GROUP |
| ISSN: | 1468-2060 0003-4967 |
| DOI: | 10.1136/annrheumdis-2019-215698 |
| Popis: | ObjectiveAnti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains). Recently, we showed that N-glycosylation sites, which are required for the incorporation of V-domain glycans, are introduced following somatic hypermutation. However, it is currently unclear when V-domain glycosylation occurs. Further, it is unknown which factors might trigger the generation of V-domain glycans and whether such glycans are relevant for the transition towards RA. Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.MethodsACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).ResultsV-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset. Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.ConclusionOur observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life. Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA. |
| Databáze: | OpenAIRE |
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