Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

Abstract

Inborn errors of immunity (IEI) are multifaced diseases which can present with a variety of phenotypes, ranging from infections to autoimmunity, lymphoproliferation, and neoplasms. In recent decades, research has investigated the relationship between autoimmunity and IEI. Autoimmunity is more prevalent in primary humoral immunodeficiencies than in most other IEI and it can even be their first manifestation. Among these, the two most common primary immunodeficiencies are selective IgA deficiency and common variable immunodeficiency. More than half of the patients with these conditions develop non-infectious complications due to immune dysregulation: autoimmune, autoinflammatory, allergic disorders, and malignancies. Around 30% of these patients present with autoimmune phenomena, such as cytopenia, gastrointestinal and respiratory complications, and endocrine and dermatologic features. Complex alterations of the central and peripheral mechanisms of tolerance are involved, affecting mainly B lymphocytes but also T cells and cytokines. Not only the immunophenotype but also advances in genetics allow us to diagnose monogenic variants of these diseases and to investigate the pathogenetic basis of the immune dysregulation. The diagnosis and therapy of the primary humoral immunodeficiencies has been mostly focused on the infectious complications, while patients with predominant features of immune dysregulation and autoimmunity still present a challenge for the clinician and an opportunity for pathogenetic and therapeutic research.

Crosstalk between Inflammation and Atherosclerosis in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Is There a Common Basis?

“…In addition, emerging evidence points to a role of viral and bacterial triggers in the pathogenesis of atherosclerosis [ 39 ], triggers that are also implicated in the pathogenesis of autoimmune diseases [ 40 ], hepatitis viruses, periodontal bacteria, LPS, etc., due to molecular mimicry phenomena. Further research has revealed the presence of autoantibodies that can enhance the inflammatory process, such as antibodies against glucose-regulated protein 78 (GRP78) and those against heat shock proteins 60 and 90 (HSP60, HSP90) [ 39 ].…”