A Comparison of Immunoglobulin Variable Region N-Linked Glycosylation in Healthy Donors, Autoimmune Disease and Lymphoma
| Autor: | Esther M. Vletter, Marvyn T. Koning, Hans Ulrich Scherer, Hendrik Veelken, Rene E. M. Toes |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Glycan Glycosylation glycosylation Immunology Immunoglobulin Variable Region B-cells Somatic hypermutation lymphoma Review medicine.disease_cause Anti-Citrullinated Protein Antibodies Autoimmune Diseases Autoimmunity Arthritis Rheumatoid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Protein Domains N-linked glycosylation Polysaccharides Lectins Myasthenia Gravis medicine Humans Lupus Erythematosus Systemic Immunology and Allergy antibodies Genetics Autoimmune disease biology autoimmunity Autoantibody medicine.disease carbohydrates (lipids) 030104 developmental biology chemistry biology.protein Antibody lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in Immunology, Vol 11 (2020) Frontiers in Immunology, 11. FRONTIERS MEDIA SA Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | N-linked glycans play an important role in immunity. Although the role of N-linked glycans in the Fragment crystallizable (Fc) region of immunoglobulins has been thoroughly described, the function of N-linked glycans present in Ig-variable domains is only just being appreciated. Most of the N-linked glycans harbored by immunoglobulin variable domain are of the complex biantennary type and are found as a result of the presence of N-linked glycosylation that most often have been introduced by somatic hypermutation. Furthermore, these glycans are ubiquitously present on autoantibodies observed in some autoimmune diseases as well as certain B-cell lymphomas. For example, variable domain glycans are abundantly found by anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) as well as by the B-cell receptors of follicular lymphoma (FL). In FL, variable domain glycans are postulated to convey a selective advantage through interaction with lectins and/or microbiota, whereas the contribution of variable domain glycans on autoantibodies is not known. To aid the understanding how these seemingly comparable phenomena contribute to a variety of deranged B-responses in such different diseases this study summarizes the characteristics of ACPA and other auto-antibodies with FL and healthy donor immunoglobulins, to identify the commonalities and differences between variable domain glycans in autoimmune and malignant settings. Our finding indicate intriguing differences in variable domain glycan distribution, frequency and glycan composition in different conditions. These findings underline that variable domain glycosylation is a heterogeneous process that may lead to a number of pathogenic outcomes. Based on the current body of knowledge, we postulate three disease groups with distinct variable domain glycosylation patterns, which might correspond with distinct underlying pathogenic processes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|