The Role of Complement in the Development of Systemic Lupus Erythematosus

Abstract

Complement has both beneficial and deleterious roles in the pathogenesis of systemic lupus erythematosus (SLE). On the one hand, patients with SLE present with decreased complement levels and with complement deposition in inflamed tissues, suggestive of a harmful role of complement in the effector phase of disease. On the other hand, homozygous deficiency of any of the classical pathway proteins is strongly associated with the development of SLE. There are two main hypotheses to explain these observations. The first invokes an important role for complement in the physiological waste-disposal mechanisms of dying cells and immune complexes. The second hypothesis is based around the role of complement in determining the activation thresholds of B and T lymphocytes, with the proposal that complement deficiency causes incomplete maintenance of peripheral tolerance. These two hypotheses are not mutually exclusive. In addition, there is evidence for a contribution from other genetic factors in determining the phenotype of disease in the absence of complement.

Markers of childhood lupus nephritis indicating disease activity

“…Soluble VCAM-1 (sVCAM-1) has been reported as a useful marker of adult SLE activity [9,10]. On the other hand, deficiency of the early classical pathway component C1q induces tissue damage [11,12] and the occurrence of autoantibodies to C1q in SLE has been shown to be associated with hypocomplementemia and severe active LN [13][14][15].…”

Immunological mechanisms and clinical implications of regulatory T cell deficiency in a systemic autoimmune disorder: Roles of IL‐2 versus IL‐15

“…In contrast to B cell hyperactivity [3], reduced IL-2 production and hyporesponsiveness of T cells are characteristic of SLE [4,5]. Moreover, impaired cellular immunity, complement deficiency, defects in the clearance of dying cells by macrophages [6][7][8], and the disrupted mechanisms of tolerance induction [9][10][11] are among many immunological characteristics of, or potential mechanisms proposed for, the disease.…”

Bioinformatic identification of genes encoding C1q-domain-containing proteins in zebrafish

“…In invertebrate and even bacterial species, we also identified C1qDC proteins, whereas in many species that have a more recent evolutionary history with zebrafish, we did not find the homologous sequences for encoding C1qDC proteins. In human and in mouse, deficiency of C1q is strongly associated with the development of systemic lupus erythematosus (SLE) (Manderson et al, 2004). However, we haven't found the exactly complement C1q in non-mammal animals until now.…”