Tonsil-induced autoimmune/inflammatory syndrome: Current insights into the pathogenic role of tonsils in immunoglobulin a nephropathy, palmoplantar pustulosis and psoriasis

Abstract

The tonsils, specifically the palatine tonsils, serve as a first line of defense against pathogenic microorganisms that enter the nasal or oral cavity. They release antigen-specific immune cells and antibodies that circulate not only in the upper respiratory tract but also throughout the rest of the body. Numerous clinical studies, including randomized prospective trials, have shown that tonsillectomy is highly effective in treating immunoglobulin A nephropathy (IgAN), palmoplantar pustulosis (PPP), and psoriasis. However, the precise pathogenic association of the tonsils with these diseases remains incompletely understood. The author previously proposed the concept of tonsil-induced autoimmune/inflammatory syndrome (TIAS) as a common underlying mechanism for these diseases. TIAS suggests that an excessive immune response initiated by the tonsils, often triggered by common bacteria such as α- and β-hemolytic streptococcus and Haemophilus parainfluenzae, which are indigenously present in the oral cavity, can become dysregulated. This immune response also involves unmethylated DNA sequences (CpG-ODN) that are shared among various bacteria. In reaction to these bacteria or CpG-ODN, tonsillar T-cell populations, including type 17 helper T (Th17), Th22, Th1, and cytotoxic T cells, become proliferative. Simultaneously, tonsillar B-cell populations responding to these triggers produce antibodies against epidermal keratins and heat shock proteins, or aberrant IgA1. These tonsillar T-cell populations and the antibodies then enter the systemic circulation, migrating to the kidneys or skin. Upon reaching the organs, they contribute to tissue damage, aided by various cytokine actions. IgAN, PPP, and psoriasis, which are representative disorders of TIAS, all share this common pathogenic mechanism. In this article, the author discusses the pathogenesis of TIAS based on recent research findings.