Classification of Inborn Errors of Immunity: Implications for Diagnosis and endocrinology Management

Classification of Inborn Errors of Immunity: Implications for Diagnosis and Management Background: Inborn errors of immunity (IEI) are a heterogeneous group of genetically driven disorders that impair the function of one or more component of immunity. With rapid progress in genomic technologies, the classification of IEI has evolved substantially to reflect clinical and molecular diversity. Objective: To present an updated classification framework of IEI that integrates new genetic discoveries and highlights clinical phenotypes. Methods: A comprehensive review of recent high-impact literature was conducted, focusing on the categorization of IEI by affected immune pathways, clinical features, and molecular defects. Results: Nearly ۵۵۵ different disorders have been genetically identified, with new disorders continually being recognized. Most IEIs are from germline mutations. Whereas, some are acquired which are called phenocopies. Current IEI classification encompasses ۱۰ principal categories based on the ۲۰۲۴ classification by the International Union of Immunological Societies (IUIS) Expert Committee: combined immunodeficiencies, combined immunodeficiency with syndromic features, predominantly antibody deficiencies, immune dysregulation disorders, autoinflammatory diseases, congenital defects of phagocyte number/function, defects in intrinsic and innate immunity, and complement deficiencies, bone marrow failure, and phenocopies of inborn error of immunity. Molecular diagnostics based on gene panels and whole-exome sequencing, facilitating early diagnosis. Although, immunological testing remains vital for phenotype confirmation. This classification may facilitate early diagnosis and recognition of the disease, enabling tailored precision medicine with biological therapies, thereby improving patient outcomes. Conclusions: IEI classification reflects the complexity of immune system impairment and guides personalized diagnostic and management strategies.