Predominantly Antibody Deficiencies Publisher



Abolhassani H ; Aghamohammadi A ; Plebani A ; Lougaris V ; Durandy A ; Condinoneto A ; Kanegane H ; Hammarstrom L
Source: Inborn Errors of Immunity: Definition, Diagnosis, and Management Published:2025

Abstract

Predominantly antibody deficiency (PAD) seem to be the most common subcategory of inborn errors of immunity characterized by low immunoglobulin serum levels in the presence or absence of B cells. Thus, poor humoral immunity makes PADs prone to recurrent infections, immune dysregulation and cancer. Broad clinical phenotypes and complex immunologic profiles in PAD patients have led to diagnostic difficulties and long delays for appropriate treatment, which increase the life-threatening complications in these patients. PAD is one of the main inborn errors of immunity categories which majority of patients are without defined monogenic molecular pathogenesis despite routine genetic analysis. Despite the above-mentioned molecularly unsolved PAD patients, next generation sequencing is still an important tool in identifying the underlying genetic diagnoses of a minority of these patients. Many of the known 508 genes underlying inborn errors of immunity (both intrinsic or extrinsic B cell defect) have been described in the past decade with defects in antibody production. Ultimately, during the past decades, better insights into molecular diagnosis and clinical prognosis have contributed to the understanding of the immunological mechanism of PAD patients. Immunoglobulin replacement therapy, as one of the most important treatments for PAD patients since 1981, can be sufficiently compelling for preventing infections and treating inflammatory complications. The advances in treatment and improvement of personalized therapies aim for a better quality of life for these patients. The Algorithm Diagram 4.1 shows the phenotypic classification of predominantly antibody deficiencies. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2025.