Primary minor immunodeficiencies as a cause of immunodependent pathology in humans: Etiology, epidemiology, classification, diagnosis, and treatment (Systematic review)

Deficiencies in immune protection (both congenital and acquired through life) significantly influence a human’s life quality. Primary minor immunodeficiencies (PMDs) are more common in the population than classical immunodeficiencies and place a high burden on society. However, the evidence on PMDs is not systematized. The aim of the current research became the analysis and synthesis of the evidence on etiology, epidemiology, diversity, clinical manifestations, diagnosis, and treatment of PMD in humans to synthesize a scientific concept. In this way, the systematic review of publications from PubMed and SCOPUS databases has been conducted by the keywords. The time of analysis was the period from 1960 to 2025. Out of 2937 primary publications, 424 that met the selection criteria were included in the final list. As a result, terminology, genetic heterogeneity, epidemiology, spectrum of manifestation, structuring of clinical syndromes, and classification of PMD were clarified due to the current research. A distinction is made between PMD and classical immunodeficiencies. The algorithms of diagnostics and immunotherapeutic interventions were considered. The scientific concept of PMD diagnosis and treatment was proposed, which presents PMDs as a universal natural model of the development of different human immune-dependent pathologies on a population scale. PMDs, by their prevalence in the population, diversity, and degree of clinical manifestation, can explain the development of the entire described spectrum of immunodependent diseases in humans. The proposed PMD concept can allow optimizing the clinical management of patients with associated immunodependent pathology using an integrative personalized multidisciplinary approach with the availability of etiology estimation and etiotropic treatment providing.