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

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.

SUBMITTER: Bende RJ

PROVIDER: S-EPMC11231493 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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

Bende Richard J RJ Donner Naomi N Wormhoudt Thera Am TA Beentjes Anna A Scantlebery Angelique A Grobben Marloes M Tejjani Khadija K Chandler Felicity F Sikkema Reina S RS Langerak Anton W AW Guikema Jeroen Ej JE van Noesel Carel Jm CJ

Life science alliance 20240708 9

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 intr ...[more]

PMID: 38977312

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Project description:BackgroundThe choice of a primary treatment for ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) depends on the extent of tumor spread. However, radiotherapy is commonly used as a first-line therapy despite ophthalmic complications, because most OAMLs are in a limited stage of progression. However, the initial therapeutic modality, including chemotherapy and treatment of the advanced stage, has not been fully established for OAML. Therefore, we evaluated the optimal therapeutic options and survival outcome-related parameters for patients with primary OAML.MethodsWe evaluated 208 consecutive patients with primary OAML who were diagnosed at the Catholic University Lymphoma Group between January 2004 and April 2015.FindingsDuring a median follow-up of 70.0 months (range, 3.2-182.0 months) in 208 patients with primary OAML, most patients were female and the median age was 46 years old. Overall survival (OS) and progression-free survival (PFS) at 13 years were excellent (92.7% and 69.7%, respectively). Of the 117 patients who received the first-line radiotherapy, 92% achieved complete remission (CR), usually by being treated with less than 30 Gy. Radiation-related ophthalmic complications including dry eye syndrome (59%) and cataract (22%) caused a decline in the quality of life (QoL). Chemotherapy alone was used to treat 86 OAML patients, with 84.9% achieving CR and 12.8% achieving partial remission with tolerable toxicities. There were no differences in survival outcomes between patients treated with radiotherapy versus those treated with rituximab-containing chemotherapy, although the latter group had more advanced stages of OAML (OS, p = 0.057; PFS, p = 0.075).InterpretationOAML patients were predominantly female and relatively young, and radiotherapy as a primary therapeutic option was more likely to lead to radiation-related complications, resulting in lower QoL. On the other hand, frontline chemotherapy showed consistent therapeutic outcomes with tolerable toxicities compared to radiotherapy, and there were no long-term or delayed adverse events. Therefore, when considering therapeutic efficacy and therapy-related QoL, chemotherapy is recommended for younger patients, and radiotherapy is recommended for older and chemotherapy-ineligible patients.FundingA National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. NRF-2016R1A2B4007282).

Dataset Information

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

Publications

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

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