clinical outcomes of a cohort of patients with cd40l deficiency

Introduction: cd40 ligand (cd40l) deficiency is an x-linked form of hyper immunoglobulin m syndrome (xhigm), which is caused by mutations of cd40lgene. the aim of the present study was to investigate the clinical and molecular basis of this disorder with a long period of follow-up on an iranian patients group. methods: totally, 21 patients diagnosed with xhigm, who were referred to at children’s medical center (pediatrics center of excellence affiliated to tehran university of medical sciences, tehran, iran), and then were followed up, were enrolled in this retrospective cohort study. the medical and immunologic evaluations of patients were followed by mutation analysis to confirm the diagnosis. results: the median age of all participants was 7.50 (4.87-16.25) years old. the median age at the time of disease onset was 8.00 (6.00-13.50) months. also, majority of patients showed their first manifestation before the age of 4 years old. the median age of diagnosis was 23.00 (12.50-48.00) months, with a median diagnostic delay of 9.00 (1.50-28.00) months. anemia was the most frequent hematologic manifestation, which was occurred in 71.4% of the patients. the median serum igm concentration was 206 (82-335) mg/dl. six patients had normal igm levels, however, elevated igm levels were observed in fifteen patients based on age-references. the mutation analysis among patients with the cd40l mutations revealed 15 missense, 5 frame hiftnonsense, and 1 splice-site mutation. eight patients (38%) died in this study duration period. respiratory infection such as pneumonia were the main cause of death in 5 patients. conclusions: earlier diagnosis of x-higm may provide effective management and lead to patients’ survival, and consequently better quality of life. moreover, using whole-exome sequencing for detecting those patients with higm phenotype is strongly recommended in order to differentiate it from intrinsic humoral immunity defects and also to initiating the appropriate therapeutic procedures and management.