Activation of the complement system in human immunodeficiency virus infection: relevance of the classical pathway to pathogenesis and disease severity.
In vitro studies implicate classical and alternative complement pathway activation in the pathogenesis of human immunodeficiency virus (HIV) infection. To ascertain 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 beta 2-microglobulin, neopterin, and CD4-positive (CD4+) lymphocyte levels. All fragments and ratios were significantly higher in patients (P less than .01) than controls. C4 conversion indices (C4d and C4d to C4) increased linearly with increasing CDC stage (P less than .001), while CD4+ lymphocytes decreased linearly (P less than .001). C4d, C3d, C4d to C4, and C3d to C3 correlated with increasing CIC and beta 2-microglobulin, and C4d and C4d to C4 correlated with decreasing CD4+ lymphocytes (P less than .05). The relationship of classical complement pathway activation to disease progression and CD4+ lymphocytes suggests its involvement in the pathogenesis of HIV infection.
Senaldi
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Department of Immunology, King's College School of Medicine and Dentistry, London, United Kingdom.
Peakman
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M
McManus
T
T
Davies
E T
ET
Tee
D E
DE
Vergani
D
D
D000328:Adult; D000936:Antigen-Antibody Complex / Q000097:blood; D001708:Biopterins / Q000031:analogs & derivatives / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes; D015933:Complement C3d / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D015935:Complement C4b; D011415:Complement Factor B / Q000032:analysis; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D005260:Female; D015658:HIV Infections / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D019798:Neopterin; D010446:Peptide Fragments / Q000032:analysis; D012044:Regression Analysis; D001613:beta 2-Microglobulin / Q000032:analysis
D000936:Antigen-Antibody Complex; D003181:Complement C4; D010446:Peptide Fragments; D001613:beta 2-Microglobulin; D001708:Biopterins; D019798:Neopterin; D015933:Complement C3d; D015935:Complement C4b; C032261:complement C4d; D011415:Complement Factor B