Analysis of B cell selection in autoimmune diseases
PhD ceremony: Ms. N. Hamza, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen
Dissertation: Analysis of B cell selection in autoimmune diseases
Promotor(s): prof. N.A. Bos, prof. C.G.M. Kallenberg, prof. F.G.M. Kroese
Faculty: Medical Sciences
In this thesis, we studied patients with the autoimmune disease primary Sjorgen Syndrome (pSS) who were treated with a B cell-targeting therapeutic antibody (rituximab, RTX). Immunoglobulin variable heavy chain gene (IGHV) sequences were used as B cell markers to trace the presence of B cell clonal populations before and after treatment. Significantly increased clonal expansions in salivary glands of pSS patients and a prevalence of acquired N-glycosylation motifs (ac-Nglycs) in their IgG sequences were observed. Also a strong emphasis on conservation of IgG framework regions in pSS patients compared to non-pSS controls was seen. Treatment with RTX failed to reset these core characteristics of immunoglobulin (Ig)-producing cell populations in pSS patients. This suggested that Ig-producing cells which persisted after RTX could contribute to the disease relapse observed after RTX. This study is the first to suggest that a proportion of B-cells in pSS patients could be selected on the basis of ac-Nglycs in their Ig variable regions. Further studies clearly indicated a similar selection of B cells in other autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. The presence of ac-Nglycs within IGHV sequences from certain autoimmune diseases could indicate an unconventional selection pressure that enables B-cells with glycosylated BCRs to engage, survive and persist within autoimmune lesions through their interaction with lectin-expressing cells such as dendritic cells or macrophages.
Last modified: | 13 March 2020 01.00 a.m. |
More news
-
06 May 2024
Impact: 'URinControl', treatment of urine loss through app
One of the three researchers nominated for the Ben Feringa Impact Award 2024 is general practicioner and researcher-epidemiologist Anne Loohuis. Loohuis conducted research on the treatment of urine loss through the self-help app URinControl'.
-
29 April 2024
Tactile sensors
Every two weeks, UG Makers puts the spotlight on a researcher who has created something tangible, ranging from homemade measuring equipment for academic research to small or larger products that can change our daily lives. That is how UG...
-
29 April 2024
Royal Decoration awarded to Gerard van den Berg
The Faculty of Economics and Business is very proud to announce that Professor Gerard van den Berg has been appointed Officer of the Order of Orange-Nassau. The decoration was presented to him by Mayor Koen Schuiling of the Municipality of...