Year: 2026
Type: article
Abstract: Immune dysregulation is being increasingly recognized as a prominent feature of a wide range inborn errors of immunity (IEIs) with different molecular backgrounds. Among the manifestations of immune dysregulation, inflammatory arthritis has emerged as an important yet underrecognized complication that may occur across multiple IEI categories, including humoral immunodeficiencies (such as X-linked agammaglobulinemia, hyper-IgM syndrome, common variable immunodeficiency, and others), complement deficiencies, disorders of immune dysregulation (STAT3 gain of function mutation, CTLA4 and LRBA haploinsufficiency), and combined immunodeficiencies. In some patients, arthritis may represent the first or predominant clinical manifestation, resulting in a diagnostic challenge in the rheumatologic setting. The pathogenesis of arthritis in IEIs reflects different immunological mechanisms, including the defective clearance of immune complexes, dysregulated B- and T-cell responses, impaired regulatory T-cell function, and aberrant cytokine signaling. Clinically, IEI-associated arthritis may mimic classical rheumatologic conditions such as juvenile idiopathic arthritis, rheumatoid arthritis, or other connective tissue diseases, although distinctive immunological and histopathological features are often present. Recognizing arthritis as a potential manifestation of IEIs has important clinical implications. The presence of specific "red flags", including treatment refractoriness, recurrent infections, or additional signs of immune dysregulation (other autoimmune diseases, atopy, lymphoproliferation, enteropathy), should prompt targeted immunological evaluation. While management often relies on conventional immunosuppressive therapies, advances in the molecular characterization of IEIs are increasingly enabling the use of targeted treatments directed at the underlying pathogenic mechanisms. This paper provides an overview of the current knowledge of arthritis associated with IEIs, highlighting diagnostic challenges, underlying immunopathogenic mechanisms, and emerging therapeutic perspectives.
Source: Journal of Clinical Medicine
DOI: 10.3390/jcm15093298
Institutions: University of Pisa, Azienda Ospedaliera Universitaria Pisana
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,137
OpenAlex ID: W7157277320