Wen-I Lee, Taiwan
Chang Gung Memorial Hospital and Chang Gung University PediatricsPresenter of 1 Presentation
THE NOVEL CD3G MUTATION WITH THE PREDOMINATELY B CELL-DEFICIENCY PRESENTATION AND PHENOTYPE/GENOTYPE COMPARISON IN ALL MUTATIONS
Abstract
Background and Aims
TCR/CD3 complex is crucial for the development and regulation of T cells. In humans, CD3D, CD3E, and CD3Z gene defects cause severe immune deficiency and present early in life with increased susceptibility to infections. By contrast, CD3G mutations lead to milder phenotypes, mainly characterized by autoimmunity.
Methods
Bearing recurrent sinopulmonary infections without opportunistic infections compatible to hypogammaglobuliemia but normal PHA lymphocyte proliferation, a male 36-year-old adult receives genetic analysis after regular IVIG over 15 years. His lymphocyte subsets, CD3 expression, T regulatory (Treg) cells and suppression are assessed. To comprehensively review this rare disease, we analyze the phenotypes, genotypes, treatment and prognosis from a PubMed search to hopefully guide optimal management.
Results
In contrast to the previous CD3G mutations presenting as autoimmunity, the novel CD3G mutation maintains sufficient Treg number and suppression makes him free of autoimmunity of autoimmune thyroiditis, inflammatory bowel disease, and pancytopenia. CD27+memory B cells are almost absent. Pubmed research reveals 7 Turkish and 2 Spanish patients (5 unrelated families). They are the splicing mutations 80(-1)G>C (in 14), missense mutations c.1G>A (2), and nonsense mutations c.250A>T (2). Three only present with isolated autoimmune thyroiditis without significant infections. Only our patient has neither any autoimmunity nor detectable autoantibody. Three mortalities were severe infection at 31 months, post-transplant viral pneumonia at 17 months and graft vs host disease (GvHD) at 47 months.
Conclusions
With the novel CD3G mutation, the patient presents as predominantly B cell deficiency mimicking the CVID phenotype and lacking the recognizable autoimmunity. This finding expands the phenotype in patients with CD3G mutations.