Maternal serum α-fetoprotein and human chorionic gonadotropin levels in women with human immunodeficiency virus

Abstract

To the Editors: We have read with great interest the article by Gross et al1.Gross S. Castillo W. Crane M. Espinosa B. Carter S. DeVeaux R. et al.Maternal serum α-fetoprotein and human chorionic gonadotrophin levels in women with human immunodeficiency virus.Am J Obstet Gynecol. 2003; 188: 1052-1056Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar on maternal serum alpha-fetoprotein (MSAFP) and human chorionic gonadotropin (hCG) levels in pregnant women with human immunodeficiency virus (HIV). In their discussion, the authors proposed 2 hypotheses to explain their findings of elevated MSAFP with increased viral load and decreased CD4 counts with hCG. Having discounted chronic placental damage as the first possible cause of elevated MSAFP levels, the authors favored maternal AFP immunoregulatory activity during the course of the HIV disease. During the last 20 years, the immunoregulatory role of human AFP, in contrast to that of rodent AFP, has remained highly controversial and largely unconfirmed, with results difficult to duplicate among laboratories. Indeed, the references cited to support their contention of an AFP immunoregulatory role employed largely rodent cells, which were used as in vitro systems in studies performed during the 1970s. However, more recent research has addressed the physiologic and biochemical aspects of AFP interaction with monocyte/macrophage membrane receptor complexes. Studies by Uriel et al2.Uriel J. Lunardi-lskandar Y. Labordo I.L. Torres J.M. Naval J. Ceorgoulias V. et al.Defective uptake of alpha-fetoprotein (AFP) and transferring (Tf) by PHA-activated peripheral blood lymphocytes from patients with AIDS and related syndromes.AIDS Res Hum Retroviruses. 1990; 6: 401-410Crossref PubMed Scopus (8) Google Scholar have shown that monocytes/macrophages from patients with acquired immunodeficiency syndrome (AIDS)-related disorders display defective AFP-cell surface signaling pathways, loss of membrane fluidity, altered endocytotic trafficking, and a reduction in cell-surface cytokine receptors. More recently, human (H) AFP was found to bind to CCR5 receptors at both high- and low-affinity binding sites localized on human monocyte-derived macrophages in vitro.3.Atemezem A. Mbemba E. Marfiang R. Vaysse J. Pontet M. Saffar L. et al.Human AFP binds to primary machrophages. Biochem.Biophys Res Comm. 2002; 296: 507-514Crossref PubMed Scopus (26) Google Scholar The CCR5 chemokine receptor (M-trophic) serves as a coreceptor to the CD4 major receptor for HIV intake and transfection. In this latter report, HAFP was reported to displace the dade-B HIV gp 120-VC3 loop from its binding to the CCR5 receptor on the macrophage cell surface; conversely, CCR5 ligands were found to displace HAFP from its binding to the macrophage cell surface receptor. Therefore, we propose that HAFP binding to the macrophage/monocyte at the placental interface might enhance the fetal-to-maternal gradient of AFP placental transport, thus increasing AFP levels in the maternal circulation. It is tempting to speculate that the positive correlation observed between increasing viral load and elevation of MSAFP is related to AFP sterochemical interference with viral fusion to the CD4+ cell surface receptor and its coreceptors, thus impairing viral transmission and down-regulating the CD4 counts. In this regard, it should be noted that all HIV-infected mothers in the study had normal pregnancy outcomes in that none of the screened infants, followed-up for 1 year, developed HIV. Therefore, AFP intervention may provide at least 1 explanation for the lower incidence of HIV vertical transmission from mother to fetus in the second trimester.4.Pascual A. Brina I. Cerrolaza J. Moreno P. Amos J.T. Noriega A.R. et al.Absence of maternal-fetal transmission of HIV-type-l to second trimester fetuses.Am J Obstet Gynecol. 2000; 183: 638-642Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar