Investigation of immune markers that may explain association of CMV antibody titres and cardiovascular risk in HIV+ individuals stable on HAART
HIV patients stable on HAART have both high plasma cytomegalovirus (CMV) antibody titres and increased risk of cardiovascular disease (CVD), parameters that correlate in healthy persons. We examined the contribution of immune activation and autoimmunity to this correlation in HIV+ individuals stable on HAART.
Plasma samples from 70 HIV+ individuals stable on HAART for 14(2-29) years and 120 age-matched healthy controls were assayed for total immunoglobulin G (IgG) reactive with CMV, human fibroblasts, HIVgp41, cardiolipin and immunoglobulins (GAM) reactive to heterologous smooth muscle. A correlation between anti-cardiolipin and anti-HIVgp41 antibodies was sought as evidence for cross reactivity. Samples from HIV+ individuals were further assayed for the immune activation markers sCD40L, sCX3CL1 and sTNFR. Patients attended clinic at St Vincent’s Hospital, Darlinghurst NSW. Clinical data were compiled and Framingham scores calculated to assess of risk of CVD.
CMV antibody titres correlated with Framingham scores (p=0.009, Spearman R=0.317). Nadir CD4 T-cell counts displayed a strong inverse relationship with CMV antibody (p=0.0004, Spearman R=-0.42). A multivariate model identified nadir CD4 T-cell count, Framingham score, total IgG, sCD40L and sCX3CL1 as factors associating with levels of CMV antibody. There was no association with sTNFR. Preliminary data suggests HIV patients have higher levels of CMV antibody and a higher incidence of anti-smooth muscle antibody than healthy controls. Anti-smooth muscle antibody levels correlated with total IgG and anti-CMV pp65 in HIV+ individuals. The incidence of anti-cardiolipin antibodies was higher in HIV patients than healthy controls.
Elevation of CMV antibodies in HIV patients is not a simple consequence of generalised immune activation but may reflect high antigenic load before HAART. Anti-smooth muscle antibodies show a strong relationship with B-cell activation as measured by total IgG. Associations between CMV, autoimmunity and CVD are being investigated further.
