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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Methotrexate and BAFF interaction prevents immunization against TNF inhibitors
Annals of the Rheumatic Diseases, Volume 77, No. 10, Year 2018
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Description
Objectives TNF inhibitors (TNFi) can induce anti-drug antibodies (ADA) in patients with autoimmune diseases (AID) leading to clinical resistance. We explored a new way of using methotrexate (MTX) to decrease this risk of immunisation. Methods We treated BAFF transgenic (BAFFtg) mice, a model of AID in which immunisation against biologic drugs is high, with different TNFi. We investigated the effect of a single course of MTX during the first exposure to TNFi. Wild-type (WT) and BAFFtg mice were compared for B-Cell surface markers involved in MTX-related purinergic metabolism, adenosine production and regulatory B-cells (Bregs). We translated the study to macaques and patients with rheumatoid arthritis from the ABIRISK cohort to determine if there was an interaction between serum BAFF levels and MTX that prevented immuniation. Results In BAFFtg but not in WT mice or macaques, a single course of MTX prevented immunisation against TNFi and maintained drug concentration for over 52 weeks. BAFFtg mice B-cells expressed more CD73 and CD39 compared to WT mice. MTX induced adenosine release from B cells and increased Bregs and precursors. Use of CD73 blocking antibodies reversed MTX-induced tolerance. In patients from the ABIRISK cohort treated with TNFi for chronic inflammatory diseases, high BAFF serum level correlated with absence of ADA to TNFi only in patients cotreated with MTX but not in patients on TNFi monotherapy. Conclusion MTX and BAFF interact in mice where CD73, adenosine and regulatory B cells were identified as key actors in this phenomenon. MTX and BAFF also interact in patients to prevent ADA formation. © Author(s) (or their employer(s)) 2018.
Authors & Co-Authors
Nocturne, Gaétane
France, Gif-sur-yvette
Commissariat a L'energie Atomique et Aux Energies Alternatives
France, Gif-sur-yvette
Université Paris-saclay
Roques, Pierre A.
France, Fontenay-aux-roses
Immunologie Des Maladies Virales, Auto-immunes, Hematologiques et Bacteriennes
Pruvost, A. G.
France, Gif-sur-yvette
Commissariat a L'energie Atomique et Aux Energies Alternatives
Allez, Matthieu
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Pallardy, Marc J.
France, Gif-sur-yvette
Université Paris-saclay
Le-Grand, Roger
France, Fontenay-aux-roses
Immunologie Des Maladies Virales, Auto-immunes, Hematologiques et Bacteriennes
Mariette, Xavier
France, Gif-sur-yvette
Commissariat a L'energie Atomique et Aux Energies Alternatives
France, Gif-sur-yvette
Université Paris-saclay
Statistics
Citations: 22
Authors: 7
Affiliations: 9
Identifiers
Doi:
10.1136/annrheumdis-2018-213403
ISSN:
00034967
Research Areas
Maternal And Child Health
Study Design
Cohort Study