Category: Immunodeficiency: primary or acquired
BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses.
OBJECTIVE: We intended to report most common monogenic PADs and to investigate how PAD patients who were primarily diagnosed as agammaglobulinemia, hyper IgM syndrome (HIgM) and common variable immunodeficiency (CVID) have different clinical and immunological findings.
METHODS: Stepwise next generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as agammaglobulinemia, HIgM and CVID.
RESULTS: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 BTK and 6 μ heavy chain deficiencies), HIgM (21 CD40L and 7 AID deficiencies) and CVID (17 LRBA deficiency and 12 atypical ICF syndromes) were identified. Clinical disease severity was significantly higher in patients with μ heavy chain and CD40L compared to patients with BTK and AICDA mutations. Paralysis following live polio vaccination was considerably higher in patients with μ heavy chain deficiency compared with BTK deficiency. We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in the majority of ICF patients were respiratory complications, while first presentations in LRBA patients were non-respiratory complications.
CONCLUSION: This study highlights similarities and differences in clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.