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.

Association Between Galactose-Deficient IgA1 Derived From the Tonsils and Recurrence of IgA Nephropathy in Patients Who Underwent Kidney Transplantation

“…Acute tonsillitis can aggravate IgAN; therefore, the tonsils likely produce the Gd-IgA1 that causes IgAN (30). Double immunostaining showed that the distributions of IgA and Gd-IgA1 were identical in the tonsils and glomeruli, but of the two, serum Gd-IgA1 levels were more representative of the status of IgAN progression.…”

Tonsillectomy Improved Therapeutic Response in Anti-SRP Myopathy With Chronic Tonsillitis

“…Chronic infection has long been considered a risk factor for various disorders including autoimmune diseases, since the era of ancient Mesopotamia and Greece. ( 11 , 12 ) Chronic tonsillitis has been attracting attention as a trigger of many autoimmune diseases such as IgA nephritis, IgA vasculitis, palmoplantar pustulosis, psoriasis, rheumatoid arthritis, Behçet’s disease, and myositis. Tonsillectomy has been used to alleviate these diseases.…”

“…The following mechanism has been proposed to explain the abnormal immune reaction induced by chronic tonsillitis. ( 12 ) First, indigenous unmethylated bacterial nucleotides hyperactivate immune cells (B cells, T cells, and dendritic cells) that reside in the tonsils through Toll-like receptor 9. Interferon-γ and tumor necrosis factor-α produced by activated T cells reactivate these cells and expand the population of autoreactive T cells and autoantibodies-producing B cells.…”

The analysis of treatment of Immunoglobulin A-nephropathy

“…Такие же результаты получены в крупном исследовании аналогичного дизайна [49] и метаанализов других контролируемых и ретроспективных исследований, в которых комбинация ТЭ с КС более эффективна в снижении рисков прогрессирования IgAN в сравнении с ИСТ (в основном КС) без ТЭ [44,45,49]. Эти данные позволяют предполагать, что редукция активированных В-клеток, продуцентов Gd-IgA1 и Т-клеток, принимающих непосредственное участие в патогенезе IgAN [50], в результате ТЭ может иметь стратегическое значение в изменении эволюции случаев IgAN с высокой гистологической активностью. В пользу такого предположения свидетельствуют данные повторных биопсий, показавшие более выраженную регрессию воспалительных морфологических изменений у получавших КС в сочетании с ТЭ в отличие от монотерапии КС [19,51].…”