Parvovirus B19-Induced Anemia as the Presenting Manifestation of X-Linked Hyper-IgM Syndrome

• Published in: The Journal of infectious diseases 1998-08, Vol.178 (2), p.318-324
• Main Authors: Seyama, Kuniaki, Kobayashi, Roger, Hasle, Henrik, Apter, Andrea J., Rutledge, Joe C., Rosen, David, Ochs, Hans D.
• Format: Article
• Language: English
• Subjects: Adolescent; Anemia; Anemia - complications; Anemia - genetics; Anemia - immunology; Anemia - physiopathology; Antibodies; Bacteriophages; Biological and medical sciences; Bone marrow; CD40 Ligand; Cells, Cultured; Child; DNA Mutational Analysis; Exons; Genetic Linkage; Genetic mutation; Humans; Hypergammaglobulinemia - complications; Hypergammaglobulinemia - genetics; Hypergammaglobulinemia - immunology; Hypergammaglobulinemia - physiopathology; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin M; Immunopathology; Immunophenotyping; Infections; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Ligands; Major Articles; Medical sciences; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Parvoviridae Infections - complications; Parvoviridae Infections - genetics; Parvoviridae Infections - immunology; Parvoviridae Infections - physiopathology; Parvovirus; Parvovirus B19, Human - immunology; Parvovirus B19, Human - isolation & purification; Syndrome; T lymphocytes; X Chromosome
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/515633

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 φX174, 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.