Expanding the Clinical and Genetic Spectrum of Human CD40L Deficiency: the Occurrence of Paracoccidioidomycosis and Other Unusual Infections in Brazilian Patients

Expanding the Clinical and Genetic Spectrum of Human CD40L Deficiency: the Occurrence of Paracoccidioidomycosis and Other Unusual Infections in Brazilian Patients

Author Cabral-Marques, Otavio Google Scholar
Schimke, Lena-Friederike Google Scholar
Soeiro Pereira, Paulo Vitor Google Scholar
Falcai, Angela Google Scholar
Oliveira, Joao Bosco de Google Scholar
Hackett, Mary J. Google Scholar
Errante, Paolo Ruggero Google Scholar
Weber, Cristina Worm Google Scholar
Ferreira, Janaira Fernandes Google Scholar
Kuntze, Gisele Google Scholar
Rosario-Filho, Nelson Augusto Google Scholar
Ochs, Hans D. Google Scholar
Torgerson, Troy R. Google Scholar
Costa-Carvalho, Beatriz Tavares Autor UNIFESP Google Scholar
Condino-Neto, Antonio Google Scholar
Institution Universidade de São Paulo (USP)
Univ Washington
Pediat Allergy & Immunol Clin
Albert Sabin Hosp
Pequeno Principe Hosp
Univ Fed Parana
Universidade Federal de São Paulo (UNIFESP)
Abstract CD40 ligand (CD40L) deficiency or X-linked hyper-IgM syndrome (X-HIGM) is a well-described primary immunodeficiency in which Pneumocystis jiroveci pneumonia is a common clinical feature. We have identified an unusual high incidence of fungal infections and other not yet described infections in a cohort of 11 X-HIGM patients from nine unrelated Brazilian families. Among these, we describe the first case of paracoccidioidomycosis (PCM) in X-HIGM. the molecular genetic analysis of CD40L was performed by gene sequencing and evaluation of CD40L protein expression. Nine of these 11 patients (82%) had fungal infections. These included fungal species common to CD40L deficiency (P. jiroveci and Candida albicans) as well as Paracoccidioides brasiliensis. One patient presented with PCM at age 11 years and is now doing well at 18 years of age. Additionally, one patient presented with a simultaneous infection with Klebsiella and Acinetobacter, and one with condyloma caused by human papilloma virus. Molecular analysis revealed four previously described CD40L mutations, two novel missense mutations (c.433 T>G and c.476 G>C) resulting in the absence of CD40L protein expression by activated CD4(+) cells and one novel insertion (c.484_485insAA) within the TNFH domain leading to a frame shift and premature stop codon. These observations demonstrated that the susceptibility to fungal infections in X-HIGM extends beyond those typically associated with X-HIGM (P. jiroveci and C. albicans) and that these patients need to be monitored for those pathogens.
Keywords Paracoccidioides brasiliensis
CD40 ligand
primary immunodeficiency
X-linked hyper-IgM syndrome
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Jeffrey Modell Foundation
Grant number FAPESP: 2008/06635-0
FAPESP: 2008/55700-9
Date 2012-04-01
Published in Journal of Clinical Immunology. New York: Springer/plenum Publishers, v. 32, n. 2, p. 212-220, 2012.
ISSN 0271-9142 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 212-220
Origin http://dx.doi.org/10.1007/s10875-011-9623-6
Access rights Closed access
Type Article
Web of Science ID WOS:000302615200002
URI http://repositorio.unifesp.br/handle/11600/34751

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