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Distinct groups of autoantigens as drivers of ocular adnexal MALT lymphoma pathogenesis.
Bende, Richard J; Donner, Naomi; Wormhoudt, Thera Am; Beentjes, Anna; Scantlebery, Angelique; Grobben, Marloes; Tejjani, Khadija; Chandler, Felicity; Sikkema, Reina S; Langerak, Anton W; Guikema, Jeroen Ej; van Noesel, Carel Jm.
Afiliação
  • Bende RJ; Department of Pathology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands r.j.bende@amsterdamumc.nl.
  • Donner N; Lymphoma and Myeloma Center (LYMMCARE), Amsterdam, Netherlands.
  • Wormhoudt TA; 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; Lymphoma and Myeloma Center (LYMMCARE), Amsterdam, Netherlands.
  • Tejjani K; Cancer Center Amsterdam (CCA), Amsterdam, Netherlands.
  • Chandler F; Department of Pathology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands.
  • Sikkema RS; Department of Pathology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands.
  • Langerak AW; Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands.
  • Guikema JE; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, Netherlands.
  • van Noesel CJ; Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands.
Life Sci Alliance ; 7(9)2024 Sep.
Article em En | MEDLINE | ID: mdl-38977312
ABSTRACT
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoantígenos / Imunoglobulina M / Linfoma de Zona Marginal Tipo Células B / Neoplasias Oculares Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoantígenos / Imunoglobulina M / Linfoma de Zona Marginal Tipo Células B / Neoplasias Oculares Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article