Anti-tumour necrosis factor-α antibodies and B cell homeostasis in human inflammatory bowel diseases

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Caterina Defendenti, Fabiola Atzeni, Sergio Malandrin, Sandro Ardizzone, Piero Luigi Almasio, Simone Saibeni, Cristina Bezzio, Simona Bollani, Raffaele Salerno, Paolo Declich, Zoe Sarno, Savino Bruno, Rossella Talotta, Piercarlo Sarzi-Puttini
BackgroundThe expression of CD70 on T cells is greatly enhanced by antigen-presenting cell (APC)-associated signals, such as tumour necrosis factor(TNF)-α, which is constitutionally high in patients with inflammatory bowel disease (IBD). Experimentally, the chronic activation of CD27 as a result of the constitutive expression of CD70 leads to the demise of B cells in bone marrow (BM) and the secondary lymphoid organs. The aim of this study was to assess the number and phenotype of circulating B cell in untreated IBD patients and their counterparts treated with biological anti-TNF drugs.MethodsThe study involved 13 untreated IBD patients, 36 IBD patients treated with biological drugs, and 10 healthy controls. The B cell phenotypes were assessed by means of flow cytometry using monoclonal antibodies specific for CD20, CD19, CD3, CD27 and CD43. In order to evaluate B cell development in bone marrow and peripheral B cell activation, we identified four B cell subsets: hematogones (HBs: CD20⁺19⁺3⁻27⁻43⁺), memory B cells (MBs: CD20⁺19⁺3⁻27⁺43⁻), pre-plasmablasts (PPBs: CD20⁺19⁺3⁻27⁺43⁺), and plasmablasts (PBs: CD20⁻19⁺3⁻27⁺43⁺).ResultsThe total number of B cells in the untreated patients was three times lower than that in the patients treated with biological drug (p<0.001), and half that in the healthy controls (p=0.03). The between-group differences (including the healthy donors) were statistically significant in the case of HBs and MBs, but not in the case of PPBs and PBs. Only one treated patient showed a transiently large increase in PPBs. There were statistically significant differences in all of the parameters between the untreated patients and those receiving biological therapy, and in some cases between the untreated patients and healthy controls, but never between the controls and the treated patients. Four non-responders to anti-TNF therapy had a smaller number of total circulating B cells than the untreated patients.ConclusionsAnti-TNF drugs disinhibit B cell production in IBD patients, but maintain the constant homeostasis of circulating B cells. The presence of individual variations may allow the activity of anti-TNF drugs to be monitored by studying B cell subgroups.



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