Complement, infection, and autoimmunity

Abstract

Purpose of review Complement system dysfunction in terms of upregulation, downregulation, or dysregulation can create an imbalance of both host defense and inflammatory response leading to autoimmunity. In this review, we aimed at describing the role of complement system in host defense to inflection and in autoimmunity starting from the evidence from primary and secondary complement system deficiencies. Recent findings Complement system has a determinant role in defense against infections: deficiencies of complement components are associated with increased susceptibility to infections. Primary complement system deficiencies are rare disorders that predispose to both infections and autoimmune diseases. Secondary complement system deficiencies are the result of the complement system activation with consumption. Complement system role in enhancing risk of infective diseases in secondary deficiencies has been demonstrated in patients affected by systemic autoimmune disorders, mainly systemic lupus erythematosus and vasculitis. Summary The relationship between the complement system and autoimmunity appears paradoxical as both the deficiency and the activation contribute to inducing autoimmune diseases. In these conditions, the presence of complement deposition in affected tissues, decreased levels of complement proteins, and high levels of complement activation fragments in the blood and vessels have been documented.

Alterations of Total Serum Immunoglobulin Concentrations in Pemphigus and Pemphigoid: Selected IgG2 Deficiency in Bullous Pemphigoid

“…However, this decrease was not as prominent as the reduced IgG2 concentrations in BP, but this finding also warrants follow-up and validation in prospective studies. Of note, patients with primary complement deficiencies are also prone to developing autoimmune diseases (21,22). In BP patients, plasma concentrations of C3a, C4a, and C5a are identical to those of age-and sex-matched controls (23).…”

Targeting complement cascade: an alternative strategy for COVID-19

“…Though complement is a stakeholder of a healthy immune system, uncontrolled activation of complement leads to inflammation (Conigliaro et al 2019 ). It was revealed that the viruses interact with complement components and its receptors to escape from the host-defense mechanisms (Lindahl et al 2000 ).…”

“…Duly, the complement system is a wing of an innate immune response having multifaceted biological effects against a wide range of bacterial, fungal, and viral infections. The complement cascade consists of soluble factors and cell surface receptors that can sensitize and counteract against both invading- (Stoermer and Morrison 2011 ) and self-antigens (Conigliaro et al 2019 ). The complement system bridges the innate and adaptive immune response through humoral immunity, and by modulating T- and B-cell functions (Carroll 2004 ).…”

“…In this sense, the regulation and dysregulation of complement systems and their sought-after roles in various pathological conditions have been studied (Carroll 2004 ; Guo and Ward 2005 ; Rus et al 2005 ; Conigliaro et al 2019 ). In fact, there are three main phases of complement activation such as (1) recognition of foreign molecules, (2) formation of convertase enzymes that can cleave C3 and C5, and (3) fabrication of MAC for cell lysis (Rus et al 2005 ).…”

From functions to mechanisms of the prototypic complement C5 antibody BB5.1

“…These functions have been widely researched and are not only critical for mediating protection against bacterial pathogens, 1 but can also contribute to tissue damage when dysregulated, for instance in animal models of systemic lupus erythematosus, 2 myasthenia gravis 3 and autoimmune uveoretinitis 4 . Therefore, when this system fails, as can occur in people with rare hereditary deficiencies or due to chronic inflammation, the consequences can be extremely serious, leading to persistent infections or autoimmunity 5 …”