Enteroviral meningoencephalitis as a complication of X-linked hyper IgM syndrome

• Published in: The Journal of pediatrics Vol. 134; no. 5; pp. 584 - 588
• Main Authors: Cunningham, Coleen K., Bonville, Cynthia A., Ochs, Hans D., Seyama, Kuniaki, John, Patricia A., Rotbart, Harley A., Weiner, Leonard B.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-05-1999; Elsevier; Mosby-Year Book, Inc
• Subjects: Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD40 Antigens - immunology; CD40 Ligand; DNA Mutational Analysis; Enterovirus Infections - etiology; Flow Cytometry; Genetic Linkage; Humans; Hypergammaglobulinemia - complications; Hypergammaglobulinemia - genetics; Hypergammaglobulinemia - therapy; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin A - blood; Immunoglobulin G - blood; Immunoglobulin M - blood; Immunoglobulinopathies; Immunoglobulins, Intravenous - therapeutic use; Immunopathology; Infant; Ligands; Lymphocyte Activation; Male; Medical sciences; Membrane Glycoproteins - genetics; Meningoencephalitis - etiology; Mutation; Pedigree; Pneumonia, Pneumocystis - complications; Polymerase Chain Reaction; Syndrome; X Chromosome; United States; North America; America; CD40L; PMA; TMP/SMZ; CSF; IVIG; WBC; PCP; XHIM; PCR; Human; Immunopathology; Immunoglobulinemia; Nervous system diseases; Picornaviridae; Family study; Infant; Enterovirus; Immune deficiency; Genetic determinism; IgM; Meningoencephalitis; Virus; Case study; Immunoglobulinopathy; Central nervous system disease; Complication
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/S0022-3476(99)70245-3

We describe 5 children from 2 families with mutations in the CD40 ligand (CD40L) gene leading to absent expression of CD40L on activated CD4 cells. All subjects presented with interstitial pneumonia with low serum IgG and normal serum IgM. One child had normal and one child had elevated serum IgA. Four had confirmed
Pneumocystis carinii pneumonia. In spite of intravenous immunoglobulin treatment yielding therapeutic serum immunoglobulin levels, 3 children had enteroviral encephalitis. When assessed by flow cytometry, the 3 surviving affected male children had absent CD40L expression on activated CD4
+ T cells. The affected children from both families were shown to have the same single nucleotide insertion (codon 131) resulting in frameshift and early termination within exon 4 (extracellular domain). This observation demonstrates that persistent enteroviral infection is not only observed in X-linked agammaglobulinemia but may also occur in patients with X-linked hyper IgM syndrome. (J Pediatr 1999;134:584-8)