Activation of the Complement System in Human Immunodeficiency Virus Infection: Relevance of the Classical Pathway to Pathogenesis and Disease Severity

Publisher Website
Google Scholar
Abstract
In vitro studies implicate classical and alternative complement pathway activation in the pathogenesis of human immunodeficiency virus (HIV) infection. Toascertain their importance in vivo, activation fragments of the classical (C4d), alternative (Ba), and common (C3d) pathways were measured and fragment to parent molecule ratios derived in 74 HIV-infected individuals and related to circulating immune complex (CIC) levels, Centers for Disease Control (CDC) stage, and β2-microglobulin, neopterin, and CD4-positive (CD4+) lymphocyte levels. All fragments and ratios were significantly higher in patients (P < .01) than controls. C4 conversion indices (C4d and C4d to C4) increased linearly with increasing CDC stage (P < .001), while CD4+ lymphocytes decreased linearly (P < .001). C4d, C3d, C4d to C4, and C3d to C3 correlated with increasing CIC and β2-microglobulin, and C4d and C4d to C4 correlated with decreasing CD4+ lymphocytes (P < .05). The relationship of classical complement pathway activation to disease progression and CD4+lymphocytes suggests its involvement in the pathogenesis of HIV infection.