Immunodeficiency and autoimmunity: lessons from systemic lupus erythematosus

Abstract

Recent evidence suggests that systemic autoimmunity and immunodeficiency are not separate entities, but rather interconnected processes. Immunodeficiency results from distinct defects of the immune response and primarily presents as infections, but also frequently with autoimmune features. Systemic autoimmunity is the combined effect of multiple genetic variations, infectious and immunoregulatory factors that result in dominant autoimmune manifestations in addition to frequent and opportunistic infections. The overlap in disease manifestations and symptoms suggests that immunodeficiency should be considered in the presence of autoimmunity, and vice versa. In this review, we present the shared or similar aspects of immunodeficiency and autoimmunity using systemic lupus erythematosus as a paradigm and discuss the implications for clinical care.

Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

“…Such defects though not being critical enough to allow overwhelming infections to develop, seem to provide the ideal background for chronic inflammatory responses typical of SLE (60).…”

“…Although no single pathogen (except for a putative role for Epstein-Barr virus and parvovirus B19 (61,62)) has yet been associated with SLE immunopathogenesis, recent data seem to point towards the fact that chronic inflammation in SLE could arise from chronic immune system activation towards unknown infections (60).…”

Transcription factor Ikaros Represses Protein Phosphatase 2A (PP2A) Expression through an Intronic Binding Site

“…the pathology of this disease (2). In T cells isolated from SLE patients, aberrant signaling leads to atypical characteristics, such as enhanced tyrosine phosphorylation as well as increased calcium influx (3).…”

Complement-mediated ‘bystander’ damage initiates host NLRP3 inflammasome activation

“…The third component of complement in particular represents a key opsonin that promotes the uptake of complement activators into professional phagocytes. Complement activation has long been associated with inflammation (Merle et al, 2015;Morgan, 2015) and patients deficient in complement regulatory proteins frequently suffer from inflammatory immunopathology (Grammatikos and Tsokos, 2012;Lewis and Botto, 2006;Sullivan, 1998). The multiple complement activation pathways share a common terminal pathway consisting of C5b-C9, which forms MAC on cells.…”