Elsevier

Medical Hypotheses

Volume 107, September 2017, Pages 12-13
Medical Hypotheses

IgA nephropathy during treatment with TNF-alpha blockers: Could it be predicted?

https://doi.org/10.1016/j.mehy.2017.07.016Get rights and content

Abstract

Immunoglobulin A (IgA) nephropathy (IgAN) may sometimes be related to exposure to pharmacological agents, among which anti-Tumor Necrosis Factor (TNF)-alpha agents. The characteristic pathological feature is a deposition of IgA-containing immune complexes in vessel walls in the kidney mesangium. The link between TNF-alpha blockers and IgAN may be hypothesized examining diseases which share pathologic features. In this respect, idiopathic IgAN and Henoch Schonlein Purpura have been the object of studies revealing a pathogenetic role of aberrant glycosylation of IgA1 molecules. The Authors suggest that anti-drug antibodies against glycan structures of TNF-alpha inhibitors may cross react against serum aberrant IgA1 leading to large antigen-antibody complexes. These large polymeric IgA complexes are then able to deposit in the mesangium and activate the complement cascade. Such hypothesis may be tested by measuring serum levels of galactose-deficient IgA1 of patients developing IgAN following introduction of TNF-alpha blockers. Such a test would be useful also before administration of anti-TNF alpha agents. The presence of aberrant IgA1 may represent a contraindication for treatment with TNF blockers.

Section snippets

Background

Tumor necrosis factor (TNF)-alpha is an extremely important regulatory cytokine in the immune system. The recognition of its central role in several immune‐mediated inflammatory diseases led to the introduction of a number of biologic drugs belonging of the group of TNF-alpha inhibitors [1], [2]. These drugs have been developed with the aim to produce a more targeted approach to immunomodulation [3]. TNF-alpha blockers have in fact changed the course of dermatologic, rheumatic and intestinal

Hypothesis

Patients developing IgAN after treatment with anti-TNF alpha agents may have a similar intrinsic defect in the structure of IgA1. Since aberrant glycosylation alone is insufficient to induce renal injury, the participation of antibodies directed against glycan structures of the heavy chains of TNF alpha blockers and cross-reacting with glycans on IgA1 molecules may occur. Alternatively, aberrantly glycosylated IgA1 might bind to antigenic epitopes of TNF-blockers. One way or another, large

Discussion

IgAN has been associated with several diseases, including dermatitis herpetiformis, celiac sprue and seronegative spondylarthropathies [17]. Patients with moderate-to-severe psoriasis have an increased risk of glomerular disease, particularly IgA nephropathy [18]. Psoriasis patients show elevated serum and salivary IgA levels compared with healthy individuals and with eczema. In addition patients with severe psoriasis, longer duration of disease and psoriatic arthritis have higher serum IgA

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