Dataset Information

Autoimmune lymphoproliferative immunodeficiencies (ALPID) in childhood: breakdown of immune homeostasis and immune dysregulation.

ABSTRACT: Many inborn errors of immunity (IEI) manifest with hallmarks of both immunodeficiency and immune dysregulation due to uncontrolled immune responses and impaired immune homeostasis. A subgroup of these disorders frequently presents with autoimmunity and lymphoproliferation (ALPID phenotype). After the initial description of the genetic basis of autoimmune lymphoproliferative syndrome (ALPS) more than 20 years ago, progress in genetics has helped to identify many more genetic conditions underlying this ALPID phenotype. Among these, the majority is caused by a group of autosomal-dominant conditions including CTLA-4 haploinsufficiency, STAT3 gain-of-function disease, activated PI3 kinase syndrome, and NF-κB1 haploinsufficiency. Even within a defined genetic condition, ALPID patients may present with staggering clinical heterogeneity, which makes diagnosis and management a challenge. In this review, we discuss the pathophysiology, clinical presentation, approaches to diagnosis, and conventional as well as targeted therapy of the most common ALPID conditions.

SUBMITTER: Toskov V

PROVIDER: S-EPMC10499775 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Autoimmune lymphoproliferative immunodeficiencies (ALPID) in childhood: breakdown of immune homeostasis and immune dysregulation.

Toskov Vasil V Ehl Stephan S

Molecular and cellular pediatrics 20230913 1

Many inborn errors of immunity (IEI) manifest with hallmarks of both immunodeficiency and immune dysregulation due to uncontrolled immune responses and impaired immune homeostasis. A subgroup of these disorders frequently presents with autoimmunity and lymphoproliferation (ALPID phenotype). After the initial description of the genetic basis of autoimmune lymphoproliferative syndrome (ALPS) more than 20 years ago, progress in genetics has helped to identify many more genetic conditions underlying ...[more]

PMID: 37702894

Similar Datasets

Project description:Background: Chronic silica exposure can lead to silicosis, complicated or not by autoimmune diseases (AID). The pathophysiology of silica-induced AID remains not fully understood, especially immune mechanisms that may develop in patients without yet established silicosis. We conducted a prospective clinical study to analyze the impact of crystalline silica (CS) on T cell phenotype and regulatory T cells (Tregs) frequency, as well as on auto-antibodies development in non-silicotic workers exposed to CS. Methods: Workers with moderate to high exposure level to CS and aged between 30 and 60 years-old were considered for inclusion. Peripheral blood mononuclear cells were analyzed by flow cytometry. Auto-antibodies were screened in serum by immunofluorescence. Blood from 42 and 45 healthy subjects (HC) was used as control for T cell phenotype and serum analyses, respectively. Results: Among the 63 included workers exposed to CS, 55 had full data available and were analyzed. Ten were exposed to CS for <5 years, 18 for 5-10 years and 27 for more than 10 years. The frequency of Tregs (CD4+CD25+CD127-FoxP3+) was significantly lower in CS exposed workers as compared to HC. We found an increased expression of the activation marker HLA-DR on T cells (CD3+, CD4+, and CD8+) of CS exposed workers as compared to HC. Tregs to activated T cells ratio was also lower in exposed subjects. In the latter, HLA-DR expression level and Tregs frequency were significantly associated with CS exposure duration. Serum autoantibody detection was significantly higher in CS exposed workers as compared to HC. Especially, among workers exposed more than 10 years, antinuclear antibodies and ANCA were detected in 44 and 22% among them, as compared to 5 and 2.5% in HC, respectively. Conclusion: This work shows that CS exposure is associated with a decrease of Tregs frequency, an increase of T cell activation status, and a tolerance breakdown against auto-antigens. These results show that alterations of the T cell compartment can be detected early over the course of CS exposure, preceding silicosis development or AID onset.

Dataset Information

Autoimmune lymphoproliferative immunodeficiencies (ALPID) in childhood: breakdown of immune homeostasis and immune dysregulation.

Publications

Autoimmune lymphoproliferative immunodeficiencies (ALPID) in childhood: breakdown of immune homeostasis and immune dysregulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets