Primary immunodeficiency: IPEX-syndrome. Literature review and clinical case
DOI:
https://doi.org/10.15574/SP.2022.122.63Keywords:
infants, primary immunodeficiency, IPEX-syndrome, FOXP3 gene mutations, autoimmune enteropathy, diagnosisAbstract
IPEX-syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome) is a severe inherited X-linked disease from the group of primary immunodeficiencies associated with mutations in the FOXP3 gene, which encodes a key transcription factor for T-regulatory lymphocytes. In the pathogenesis of the disease the main role plays disorder of maturation of CD25 + CD4 + -T-regulatory lymphocytes (TR), which carry out negative selection of autoreactive clones of T- and B-lymphocytes, resulting in loss of autotolerance and early development of multiorgan autoimmune pathology in combination with severe violation of antiviral and antibacterial immunity. The typical clinical picture of IPEX-syndrome is a triad: autoimmune enteropathy, endocrinopathy (diabetes mellitus type 1, autoimmune thyroiditis), skin and/or mucosal lesions, but any combination of autoimmune pathology or isolated organ damage is possible. At the same time, intestinal lesions (autoimmune enteropathy) are found in almost 100% of patients. Laboratory immunological markers of IPEX-syndrome are absent (the disease can be detected only by genetic testing - panel sequencing of genes), which, along with the variability of clinical manifestations, creates significant diagnostic difficulties.
The article presents a clinical case of IPEX-syndrome, the clinical features of which were isolated enteropathy without clinical and laboratory signs of autoimmune damage to other organs, as well as severe lesions of the small intestinal mucosa (total villi atrophy) and rapid disease progression despite late onset (during second year of life). Although immunologists associate the late onset with «soft» mutations in the gene, easier course and more favorable prognosis. Laboratory features of this case were: negative serological markers of autoimmune intestinal lesions and elevated levels of T-regulatory lymphocytes CD4 + CD25 + CD127low +, although IPEX-syndrome is characterized by a decrease or absence of T-regulatory cells.
IPEX-syndrome in this patient was confirmed by genetic research - sequencing of the FOXP3 gene revealed a pathogenic mutation с. 736-2А>Т (Splice acceptor).
The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
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