Parvovirus B19-induced anemia as the presenting manifestation of X-linked hyper-IgM syndrome.
Parvovirus B19 (B19) can cause chronic anemia due to persistent infection in immunocompromised hosts who cannot produce neutralizing antibody necessary for clearing B19. Three patients with X-linked hyper-IgM syndrome (XHIM), who were all asymptomatic until they developed B19-induced chronic anemia at the ages of 8, 14, and 17 years, respectively, were found to have mutations of the CD40L gene, including a missense mutation (T254M), a nonsense mutation resulting in a new initiation codon and loss of the intracellular domain (R11X), and a splice site mutation (nt 309+2t-->a). Antibody responses to the T cell-dependent antigen, bacteriophage phiX174, were impaired, but neutralizing antibody titers were higher than in XHIM patients with classic phenotype. All 3 patients responded to intravenous immune globulin (IVIG) treatment. Certain mutations of the CD40L gene result in a mild XHIM phenotype that may become apparent following B19 infection in patients not on IVIG therapy and therefore not protected from B19 infection.
Department of Pediatrics, University of Washington, School of Medicine, Seattle 98195-6320, USA.
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K
Seyama
R
R
Kobayashi
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H
Hasle
A J
AJ
Apter
J C
JC
Rutledge
D
D
Rosen
H D
HD
Ochs
D000293:Adolescent; D000740:Anemia / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D023201:CD40 Ligand; D002478:Cells, Cultured; D002648:Child; D004252:DNA Mutational Analysis; D008040:Genetic Linkage; D006801:Humans; D006942:Hypergammaglobulinemia / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D007075:Immunoglobulin M; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D010322:Parvoviridae Infections / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D016732:Parvovirus B19, Human / Q000276:immunology* / Q000302:isolation & purification; D013577:Syndrome; D014960:X Chromosome
D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D023201:CD40 Ligand