Recent advances in the immunological understanding of association between tonsil and immunoglobulin A nephropathy as a tonsil-induced autoimmune/inflammatory syndrome

Abstract

Introduction: Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. It is well known that upper respiratory tract infections, particularly acute tonsillitis, often worsen IgAN. Recent many clinical studies clearly show that tonsillectomy with steroid pulse therapy is the effective treatments for IgAN patients. Recently, the immunological evidence of association between tonsil and IgAN has been reported. Methods: In this review, the mechanism underlying the onset of IgAN, as a tonsil-induced autoimmune/inflammatory syndrome (TIAS), is outlined with the main focus on the authors' research results. Results: In the tonsils of patients with IgAN, hyperimmune response to the unmethylated deoxycytidyl-deoxyguanosine oligodeoxynucleotides (CpG-ODN) take place, resulting in hyperproduction of interferon-γ. The hyperproduction is followed by both overproduction of mutated IgA via B-cell activating factor (BAFF)/a proliferation-inducing ligand (APRIL)-mediated pathways and overexpression of T-cell receptor Vβ6, CXCR3, and CX3CR1 on tonsillar T cells. These IgA and T cells home to the kidney via the systemic circulation, resulting in nephritis of IgAN. Conclusions: Scientific evidence supporting the use of tonsillectomy has gradually accumulated. We hope that many additional researchers will publish new evidence linking the tonsils and kidneys in the future.