Immunoglobulin G2 Antibodies and HIV‐Infected Long‐Term Nonprogressors: What Is the Mechanism?

To the Editor—The article by Martinez et al. demonstrating that CD4 Th1 cell frequencies and IgG2 antibody titers correlated with the persistence of long-term nonprogression during HIV infection was of considerable interest [1]. Their data provide both prognostic and potentially mechanistic information that may become very valuable to clinicians and basic im-munologists. However, a word of caution is warranted with respect to the interpretation of IgG2 antibody titers. The authors may overstate matters when they indicate that human IgG2 antibodies are induced by interferon (IFN)–g and that human IgG2 antibody titers, therefore, can be used as a biomarker of Th1 cell activity in vivo. The studies cited by Martinez et al. indicating that IFN-g induces IgG2 anti-bodies are all of murine antibodies. Unfortunately , there is no direct correlation between the structure, function, activities, and/or cytokine induction of the 4 murine IgG subtypes (IgG1, IgG2a, IgG2b, and IgG3) and the 4 human IgG subtypes (IgG1, IgG2, IgG3, and IgG4) [2, 3]. Furthermore , in contrast to mice, the role played by IFN-g in the induction of IgG subtypes in humans is not well established. With respect to functional activity, of the human IgG subtypes, it is IgG3, not IgG2, that most strongly supports the cell-mediated phagocytic activities induced by IFN-g [4]. Specifically, IgG3 antibodies fix complement significantly more efficiently and bind significantly more avidly to phagocytic Fcg receptors than do IgG2 antibodies [2, 3]. In light of observations made in patients with selective IgG2 deficiency, this antibody subtype appears to be particularly important for human antibody responses to carbohydrate antigens [5–9]. How this relates to the progression of HIV infection is not immediately apparent. However, it is interesting to speculate that Martinez et al.'s impressive findings on IgG2 may suggest a mechanistic link between titers of antibodies to specific, but unknown, carbohydrate epitopes and prevention of the progression of HIV infection. Combination of HIV-1–specific CD4 Th1 cell responses and IgG2 antibodies is the best pre-dictor for persistence of long-term nonpro-gression. a healthy blood donor: concomitant lack of IgG2, IgA and IgE immunoglobulins and specific anti-carbohydrate antibodies. et al. Subclass restriction pattern of antigen-specific antibodies in donors with defective expression of IgG or IgA subclass heavy chain constant region genes. of the antibody repertoire in individuals with multiple immunoglobulin heavy chain constant region gene deletions. To the Editor—We are grateful to Spell-berg for his comments [1] regarding our article [2] demonstrating …