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Clinical and Diagnostic Laboratory Immunology, October 2005, p. 1168-1176, Vol. 12, No. 10
1071-412X/05/$08.00+0 doi:10.1128/CDLI.12.10.1168-1176.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Cryptococcus neoformans-Reactive and Total Immunoglobulin Profiles of Human Immunodeficiency Virus-Infected and Uninfected Ugandans
Krishanthi Subramaniam,1 Neil French,3,4 and Liise-anne Pirofski1,2*Departments of Microbiology and Immunology,1 Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, and Montefiore Medical Center, Bronx, New York,2 Liverpool School of Tropical Medicine, Liverpool, United Kingdom,3 Medical Research Council Programme on AIDS, Entebbe, Uganda4
Received 14 April 2005/ Returned for modification 21 June 2005/ Accepted 26 July 2005
We determined total and Cryptococcus neoformans glucuronoxylomannan (GXM)-reactive antibody repertoires of human immunodeficiency virus (HIV)-infected and HIV-uninfected Ugandans in a retrospective, case-control study of participants in a randomized controlled trial of pneumococcal vaccination. The study included 192 adults: 48 who subsequently developed cryptococcal meningitis (CM); (HIV+ CM+); 2 individuals who matched them in CD4+ T-cell level, stage of HIV disease, and age but did not develop CM (HIV+ CM–); and 48 HIV-uninfected individuals. Total serum immunoglobulin concentrations and titers of immunoglobulin M (IgM), IgG, and IgA to GXM, pneumococcal polysaccharides, and antibodies expressing certain VH3 idiotypes were determined with banked sera obtained before the development of cryptococcosis for HIV+ CM+ subjects. The results showed that HIV-infected subjects had significantly lower levels of IgM to GXM but higher levels of total immunoglobulin and IgG and IgA to GXM than those of HIV-uninfected subjects. HIV-infected subjects with a history of pneumonia had higher levels, and those with a history of herpes zoster had lower levels of GXM-binding antibodies than subjects with no history of either disease. Minimal to no cross-reactivity was demonstrated between antibodies to GXM and polysaccharides in a pneumococcal vaccine. No significant differences between the antibody repertoires of HIV+ CM+ and HIV+ CM– subjects were identified, but among subjects without a history of pneumonia, there was a trend towards lower VH3-positive antibody levels among HIV+ CM+ than among HIV+ CM– subjects. Our findings demonstrate an association between previous infectious diseases and differences in the total and GXM-reactive antibody repertoires of HIV-infected subjects and suggest the question of whether certain microbes modulate subsequent antibody responses to GXM deserves further study.
* Corresponding author. Mailing address: Division of Infectious Diseases, Albert Einstein College of Medicine, Room 709 Forchheimer, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-2372. Fax: (718) 430-2292. E-mail: pirofski{at}aecom.yu.edu.
Clinical and Diagnostic Laboratory Immunology, October 2005, p. 1168-1176, Vol. 12, No. 10
1071-412X/05/$08.00+0 doi:10.1128/CDLI.12.10.1168-1176.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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