Abstract
Background:Systemic Lupus Erythematosus (SLE) is an incurable autoimmune disorder with complement activation playing a key role in the pathogenesis of immune-mediated tissue injury. While quantifying complement to monitor SLE disease activity has been the standard of care since the 1950s, decreased complement levels are not consistently associated with flares.Objective:We seek to clarify the SLE phenotype in which complement deficiency is causative, concomitant, or coincidental.Methods:A PUBMED literature review was conducted using key words 'complement,' 'SLE,’ and ‘SLE flares’ in English-only journals from 1972-2017. Relevant clinical studies and review articles were found that examined the measurement of complement levels in SLE, and more specifically, interpretation of low serum complement levels regardless of disease activity.Conclusion:Complement activation plays a key role in the pathophysiology of SLE and it is recommended to continue monitoring serum levels of C3 and C4 to assess for disease activity. However, it is important to note that decreased serum complement is not consistently associated with disease flares.It is clinically important to find novel ways to assess disease activity in SLE. Increased serum levels of cell-bound complement activation products may more accurately reflect disease activity than conventional serum C3 and C4 monitoring.
Highlights
Systemic Lupus Erythematosus (SLE) is a heterogeneous incurable autoimmune disorder characterized by both Band T-cell dysfunction that results in immune-mediated multi-system tissue damage
A confounding factor often encountered in monitoring serum complement levels to ascertain SLE disease activity lies within the subset of SLE patients with a primary complement deficiency
Recent data has identified serum cell-bound complement activation products (CB-CAPS) with half-lives as long as the hematopoietic cells with which C3d and C4d are bound [43]. These CB-CAPS are identified in most patients with SLE and have demonstrated greater sensitivity and specificity compared to the use of low serum complements for the diagnosis of SLE [6, 44]
Summary
Systemic Lupus Erythematosus (SLE) is an incurable autoimmune disorder with complement activation playing a key role in the pathogenesis of immune-mediated tissue injury. While quantifying complement to monitor SLE disease activity has been the standard of care since the 1950s, decreased complement levels are not consistently associated with flares
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