Pathological Role of Tonsillar B Cells in IgA Nephropathy

Abstract

Although impaired immune regulation along the mucosa-bone marrow axis has been postulated to play an important role, the pathogenesis of IgA nephropathy (IgAN) is unknown; thus, no disease-specific therapy for this disease exists. The therapeutic efficacy of tonsillectomy or tonsillectomy in combination with steroid pulse therapy for IgAN has been discussed. Although randomized control trials for these therapies are ongoing in Japan, the scientific rationale for these therapies remains obscure. It is now widely accepted that abnormally glycosylated IgA1 and its related immune complex (IC) are probably key molecules for the pathogenesis, and are thus considered possible noninvasive biomarkers for this disease. Emerging evidence indicates that B cells in mucosal infections, particularly in tonsillitis, may produce the nephritogenic IgA. In this paper, we briefly summarize characteristics of the nephritogenic IgA/IgA IC, responsible B cells, and underlying mechanisms. This clinical and experimental information may provide important clues for a therapeutic rationale.

A case of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome complicated by IgA nephropathy with nephrotic syndrome

“…These antibodies often show reactivity against antigens from extrinsic microorganisms that represent subsequent hits, and they can arise following recurrent mucosal infections. Emerging evidence also indicates that B cells arising in response to mucosal infections, particularly tonsillitis, may produce the nephritogenic IgA1 molecule [14]. Tonsillar infection is also known to be involved with other diseases, including palmoplantar pustulosis, sternocostoclavicular hyperostosis, psoriasis vulgaris, nodular erythema, and rheumatoid arthritis [15], but overlap of these diseases with IgAN is rare.…”

Recurrent IgA nephropathy complicated with Crohn’s disease after renal transplantation

“…Emerging evidence indicates that B cells in mucosal infections, particularly in tonsillitis, may produce the nephritogenic IgA [7]. Tonsillectomy may affect upstream of the pathogenic mechanism by eliminating antigenic stimuli from the tonsillar mucosa.…”

The role of memory B cell in tonsil and peripheral blood in the clinical progression of IgA nephropathy

“…Impaired immune regulation along the mucosa-bone marrow axis, mainly in animal researches, has been postulated to play an important role in the pathogenesis of IgAN [14,[21][22][23][24][25]. And there exist of the hypothesis of the abnormal axis in the pathogenesis of IgAN could provide theoretical basis for tonsillectomy to cure IgAN patients, but no laboratorial evidence to support it in IgAN patients at present.…”

“…Emerging evidence indicates that B cells in mucosal infections, particularly in tonsillitis, may produce the nephritogenic IgA [14]. Then, what role does memory B cell play in the pathogenesis of IgAN, specially before and after the tonsillectomy in IgAN patients?…”