Distinct groups of autoantigens as drivers of ocular adnexal MALT lymphoma pathogenesis.

Autor:	Bende RJ; Department of Pathology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands r.j.bende@amsterdamumc.nl.; Lymphoma and Myeloma Center (LYMMCARE), Amsterdam, Netherlands.; Cancer Center Amsterdam (CCA), Amsterdam, Netherlands., Donner N; Department of Pathology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands., Wormhoudt TA; Department of Pathology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands.; Lymphoma and Myeloma Center (LYMMCARE), Amsterdam, Netherlands.; Cancer Center Amsterdam (CCA), Amsterdam, Netherlands., Beentjes A; Department of Pathology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands., Scantlebery A; Department of Pathology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands., Grobben M; Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, Netherlands., Tejjani K; Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, Netherlands., Chandler F; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands., Sikkema RS; Department of Viroscience, Erasmus MC, Rotterdam, Netherlands., Langerak AW; Department of Immunology, Laboratory Medical Immunology, Erasmus MC, Rotterdam, Netherlands., Guikema JE; Department of Pathology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands.; Lymphoma and Myeloma Center (LYMMCARE), Amsterdam, Netherlands.; Cancer Center Amsterdam (CCA), Amsterdam, Netherlands., van Noesel CJ; Department of Pathology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands c.j.vannoesel@amsterdamumc.nl.; Lymphoma and Myeloma Center (LYMMCARE), Amsterdam, Netherlands.; Cancer Center Amsterdam (CCA), Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2024 Jul 08; Vol. 7 (9). Date of Electronic Publication: 2024 Jul 08 (Print Publication: 2024).
DOI:	10.26508/lsa.202402841
Abstrakt:	Chronic B-cell receptor signals incited by cognate antigens are believed to play a crucial role in the pathogenesis of mucosa-associated lymphoid tissue lymphomas. We have explored the immunoglobulin variable regions (IGHV) expressed by 124 ocular adnexal MALT lymphomas (OAML) and tested the in vitro reactivity of recombinant IgM derived from 23 OAMLs. Six of 124 OAMLs (5%) were found to express a high-affinity stereotyped rheumatoid factor. OAMLs have a biased IGHV4-34 usage, which confers intrinsic super auto-antigen reactivity with poly-N-acetyllactosamine (NAL) epitopes, present on cell surface glycoproteins of erythrocytes and B cells. Twenty-one OAMLs (17%) expressed IGHV4-34-encoded B-cell receptors. Five of the 23 recombinant OAML IgMs expressed IGHV4-34, four of which bound to the linear NAL i epitope expressed on B cells but not to the branched NAL I epitope on erythrocytes. One non-IGHV4-34-encoded OAML IgM was also reactive with B cells. Interestingly, three of the 23 OAML IgMs (13%) specifically reacted with proteins of U1-/U-snRNP complexes, which have been implicated as cognate-antigens in various autoimmune diseases such as systemic lupus erythematosus and mixed connective tissue disease. The findings indicate that local autoimmune reactions are instrumental in the pathogenesis of a substantial fraction of OAMLs. (© 2024 Bende et al.)
Databáze:	MEDLINE
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