Complement Deficiencies in Systemic Lupus Erythematosus

Abstract

The complement system is a major, multifunctional part of innate immunity and serves as a bridge between the innate and adaptive immune systems. It consists of more than 30 distinct proteins that interact with one another in a specific sequence. There are three pathways of complement activation: the classical, the lectin, and the alternative pathways. The three pathways are initiated by distinct mechanisms, but they all generate the same core set of effector molecules. Inherited complete deficiencies in complement components are generally very rare and predispose to infections and autoimmune disease. One of the better described associations is between deficiencies in early classical pathway components and the development of systemic lupus erythematosus. The goal of this review will be to discuss the associations between and the causal mechanisms of complement deficiencies and systemic lupus erythematosus.

Complement in therapy and disease

“…Deficiencies within the early classical pathway components (C1q, C4 and C2) predispose for development of SLE, whereas complement also takes part in the auto-antibody inflammatory reaction in the disease leading to tissue and organ damage (Bryan and Wu, 2014;Truedsson et al, 2007). Reducing complement-related inflammatory responses with antibody therapeutics, potentially via the simultaneous inhibition at multiple levels could, therefore, be incorporated in future treatment regimens for SLE, RA and other autoimmune disorders.…”

Complement-Targeted Therapies in Lupus

“…Deficiency of early components of the classical complement pathway, i.e., C1q, C2, and C4, are associated with a high risk of developing lupus [6,7]. Indeed, penetrance of disease expression for C1q and C2 expression is the highest identified genetic risk for lupus [8].…”

“…The lack of these complement factors decreases clearance of immune complexes and delays clearance of apoptotic debris. These defective clearance mechanisms result in increased immune complex deposition and higher levels/longer exposure of the immune system to self-antigens [6]. Other genetic deficiencies that result in poor clearance of apoptotic debris (i.e., DNAse I and TREX1) also are associated with increased risk of lupus [10][11][12][13][14].…”

“…Other genetic deficiencies that result in poor clearance of apoptotic debris (i.e., DNAse I and TREX1) also are associated with increased risk of lupus [10][11][12][13][14]. Thus, complete inhibition of the complement pathway, especially early in the pathway, would likely be deleterious in lupus [6].…”

General Characteristics of Human Neonate Immunity

“…Patients with these disorders readily become victims of recurrent infections or systemic autoimmune diseases [75]. Complement deficiencies may involve deficiency in early complement pathway components (C1q, C1r, C2, and C4), late complement pathway components (C5, C6, C7, C8, and C9) or C3 and regulatory components [81].…”