An X-Linked Hyper-IgM Patient Followed Successfully for23 Years without Hematopoietic Stem Cell Transplantation

When caring for patients with life-limiting diseases, improving survival and optimizing quality of life are the primary goals.For patients with X-linked hyper-IgM syndrome (XHIGM), the treatment modality has to be decided for a particular patientregarding hematopoieticstem cell transplantation or intravenousimmunoglobulinreplacementtherapywithP. jiroveciprophylaxis.A seven-year-old male patient was admitted with recurrent upper and lower respiratory tract infections and recurrent otitis media.His initial immunologic evaluation revealed low IgG and normal IgA and IgM levels with normal lymphocyte phenotyping andinadequate specific antibody responses. He was diagnosed as common variable immunodeficiencyand began to receive intravenousimmunoglobulin (IVIG) (0.5 gm/kg) with four-week intervals. During follow-up for 23 years under IVIG therapy, he was extremelywell and never had severe infections. In 2017, targeted next generation sequencing was performed in order to understand hismolecular pathology. A previously described hemizygous c.31C>T(p.Arg11Ter) mutation was found inCD40LGgene. The motherwasheterozygouscarrierforthismutationandhissisterdidnothaveanymutation.FlowcytometricanalysisforCD40LGexpressionon activated T cells showed highly decreased, but not absent,CD40LGexpression. In conclusion, diagnostic delay is a clinicalproblem for patients withCD40LGdeficiency, because of low or normal IgM levels, showing that all the hypogammaglobulinemicpatients, not only with high serum IgM levels, but also with normal to low IgM levels, have to be examined forCD40LGexpressionon activated T lymphocytes. Secondly, type ofCD40LGmutations leads to enormous interpatient variations regarding serum IgMlevels, CD40LG levels on activated T cells, age at diagnosis, severity of clinical findings, and follow-up therapies with or withouthematopoietic stem cell therapy.