X-linked hyper-IgM syndrome with CD40LG mutation presents with pediatric respiratory tract infection

Background: X-linked hyper-immunoglobulin M (XHIGM), a primary immunodeficiency syndrome caused by mutations in the CD40 ligand gene, presents with recurrent respiratory infections in pediatric patients. We aimed to evaluate the spectrum of clinical features and respiratory pathogens in pediatric patients with XHIGM in China. Methods: We retrospectively reviewed seven pediatric patients who were diagnosed with XHIGM and received follow-up treatment at the Guangzhou Women and Children’s Medical Center between January 2010 and January 2021. We determined their clinical characteristics, causative pathogens, and prognosis by performing peripheral immunological and genetic tests. Results: The majority of respiratory infections in four of the seven patients were caused by Talaromyces marneffei. Two patients had viral infections caused by cytomegalovirus (CMV) and human adenovirus. One patient had a mixed infection caused by Pneumocystis carinii and CMV. Except for one child who died of respiratory failure, the other six patients survived with regular infusions of intravenous immunoglobulin (IVIg) during the follow-up period. Six patients had reduced antibody levels, especially IgG, IgA, and IgE levels. Increased serum IgM levels were detected in four cases, and three cases presented normal IgM levels at onset. All children were diagnosed with XHIGM with CD40LG variation. Three novel mutations were identified in the present study. Conclusions: Our study suggests that fungi and viruses are important pathogens causing respiratory infections in children with XHIGM. In endemic areas, children with T. marneffei infections have abnormal Ig levels in their peripheral blood, suggesting the ease of early gene detection in these patients.