Extremely prolonged HIV seroconversion associated with an MHC haplotype carrying disease susceptibility genes for antibody deficiency disorders

Alex Padiglione; Eman Aleksic; Martyn French; Alicia Arnott; Kim M Wilson; Emma Tippett; Matthew Kaye; Lachlan Gray; Anne Ellett; Megan Crane; David E Leslie; Sharon R Lewin; Alan Breschkin; Chris Birch; Paul R Gorry; Dale A McPhee; Suzanne M Crowe

doi:10.1016/j.clim.2010.07.003

Extremely prolonged HIV seroconversion associated with an MHC haplotype carrying disease susceptibility genes for antibody deficiency disorders

Clin Immunol. 2010 Nov;137(2):199-208. doi: 10.1016/j.clim.2010.07.003. Epub 2010 Aug 8.

Authors

Alex Padiglione¹, Eman Aleksic, Martyn French, Alicia Arnott, Kim M Wilson, Emma Tippett, Matthew Kaye, Lachlan Gray, Anne Ellett, Megan Crane, David E Leslie, Sharon R Lewin, Alan Breschkin, Chris Birch, Paul R Gorry, Dale A McPhee, Suzanne M Crowe

Affiliation

¹ Infectious Diseases Unit, Monash Medical Centre, Clayton, Victoria, Australia.

PMID: 20696618
DOI: 10.1016/j.clim.2010.07.003

Abstract

Severe immunodeficiency during primary human immunodeficiency virus (HIV) infection is unusual. Here, we characterized viral and immunological parameters in a subject presenting with Pneumocystis jirovecii pneumonia in the setting of prolonged primary HIV illness and delayed seroconversion. HIV antibody was only detected by enzyme-linked immunosorbent assay 12 months after presentation, and Western blot profiles remain indeterminate. Isolated virus was of R5 phenotype, exhibited poor viral fitness, but was otherwise unremarkable. Analysis of HIV antibody isotypes showed failure to mount a detectable HIV IgG response over nearly 2 years of infection, in particular IgG(1)- and IgG(3)-specific responses, despite normal responses to common infections and vaccines. Genetic analysis demonstrated homozygosity for part of an MHC haplotype containing susceptibility genes for common variable immunodeficiency (CVID) syndrome and other antibody deficiency disorders. Thus, a primary disorder of specific antibody production may explain exceptionally slow antibody development in an otherwise severe seroconversion illness. This highlights the need for multiparameter testing, in particular use of a fourth generation HIV test, for confirming HIV infection and underscores the importance of host factors in HIV pathogenesis.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies / blood
Antibodies / immunology
Antibodies, Neutralizing / immunology
Antibody Formation / immunology
Common Variable Immunodeficiency / genetics
Common Variable Immunodeficiency / immunology
Genetic Predisposition to Disease / genetics*
HIV Antigens / immunology
HIV Core Protein p24 / blood
HIV Core Protein p24 / immunology
HIV Infections / blood
HIV Infections / complications
HIV Infections / diagnosis
HIV Infections / drug therapy
HIV Infections / immunology
HIV Seropositivity / genetics*
HIV Seropositivity / immunology
HIV-1 / genetics
HIV-1 / immunology
HIV-1 / isolation & purification
Haplotypes / genetics*
Hepatitis A Vaccines / immunology
Hepatitis B Vaccines / immunology
Histocompatibility Testing
Humans
Immunoglobulin G / blood
Immunoglobulin G / immunology
Immunologic Deficiency Syndromes / genetics*
Immunologic Deficiency Syndromes / immunology
Influenza Vaccines / immunology
Major Histocompatibility Complex / genetics*
Male
Middle Aged
Neutralization Tests
Pneumocystis carinii / isolation & purification
Pneumonia, Pneumocystis / diagnosis
Pneumonia, Pneumocystis / drug therapy
Pneumonia, Pneumocystis / etiology
Pneumonia, Pneumocystis / microbiology
RNA, Viral / genetics
Receptors, CCR5 / genetics
Time Factors
Viral Load / immunology
Virus Replication / genetics

Substances

Antibodies
Antibodies, Neutralizing
HIV Antigens
HIV Core Protein p24
Hepatitis A Vaccines
Hepatitis B Vaccines
Immunoglobulin G
Influenza Vaccines
RNA, Viral
Receptors, CCR5