Affiliation:
1. Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
2. Department of Medicine, Division of Infectious Disease, University of Alabama at Birmingham, Birmingham, Alabama, USA
Abstract
Summary
The complement system is now a therapeutic target for the management of serious and life-threatening conditions such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, glomerulonephritis and other diseases caused by complement deficiencies or genetic variants. As complement therapeutics expand into more clinical conditions, monitoring complement activation is increasingly important, as is the baseline levels of complement activation fragments in blood or other body fluid levels. Although baseline complement levels have been reported in the literature, the majority of these data were generated using non-standard assays and with variable sample handling, potentially skewing results. In this study, we examined the plasma and serum levels of the soluble membrane attack complex of complement (sMAC). sMAC is formed in the fluid phase when complement is activated through the terminal pathway. It binds the regulatory proteins vitronectin and/or clusterin and cannot insert into cell membranes, and can serve as a soluble diagnostic marker in infectious disease settings, as previously shown for intraventricular shunt infections. Here we show that in healthy adults, serum sMAC levels were significantly higher than those in plasma, that plasma sMAC levels were similar between in African Americans and Caucasians and that plasma sMAC levels increase with age. Plasma sMAC levels were significantly higher in virally suppressed people living with HIV (PLWH) compared to non-HIV infected healthy donors. More specifically, PLWH with CD4+ T cell counts below 200 had even greater sMAC levels, suggesting diagnostic value in monitoring sMAC levels in this group.
Funder
Impact Fund of Children's of Alabama
National Institute of Allergy and Infectious Diseases
National Heart, Lung, and Blood Institute
University of Alabama at Birmingham
University of Washington
University of California San Diego
University of California San Francisco
Case Western Reserve University
Johns Hopkins University
Fenway Health/Harvard
University of North Carolina Chapel Hill
Publisher
Oxford University Press (OUP)
Subject
Immunology,Immunology and Allergy
Cited by
7 articles.
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