Clinical And İmmunological Features Of Three Lrba Deficiency Patients

Year 2019, Volume: 7 Issue: Ek - IRUPEC 2019 Kongresi Tam Metin Bildirileri, 54 - 56, 10.12.2019

Aylin Yücel

Abstract

LPS-responsive beige-like anchor (LRBA) deficiency is a primary immunodeficiency characterized by; recurrent sinopulmonary infections with hypogammaglobulinemia, lymphoproliferation, immunodysregulation, which presents by enteropathy, cytopenias, and autoimmune endocrinopathy.
The LRBA protein is a cytosolic protein that is expressed in several cell types including hematopoietic, neural, gastrointestinal and endocrine cells. LRBA regulates cytotoxic T lymphocyte antigen-4 (CTLA-4) turnover in endosomes. CTLA-4 is a critical and potent inhibitor of T-cell proliferation that serves as a “checkpoint” of immune responses. CTLA-4 is a crucial T-cell inhibitory receptor. CD28 is principal T-cell costimulatory molecule and critical for inducing T-cell proliferation CD28 and CTLA-4 compete for the same ligands, on the surface of antigen-presenting cells (CD80 and CD86). Moreover, CTLA-4 binds CD80 and CD86 with significantly higher affinity and avidity than CD28. CTLA4 inhibits T cell proliferation by binding to these ligands. Most CTLA-4 is stored in recycling endosomes, which cycle to the cell surface following T-cell activation. LRBA regulates intracellular CTLA-4 traffic. It prevents lysosomal degradation of CTLA4. Therefore, the inflammatory response cannot be limited in LRBA deficiency.
The clinical features are heterogeneous. Age of presentation ranging from two months to 12 years. The majority (71 %) presented at or before 5 years of age. The disease phenotype can be divided into an enteropathy phenotype, an autoimmunity phenotype and an immunodeficiency phenotype. The enteropathy phenotype includes autoimmune enteropathy, IBD/IBD-like disease and non-infectious diarrhea; the immunodeficiency phenotype includes combined immunodeficiency (CID), CVID and a CVID-like disease and the autoimmunity phenotype includes mainly AIHA and/or ITP were the most common, followed by autoimmune thyroid disease, type 1 diabetes mellitus, JIA and celiac like disease.
Case 1.
NG, 14 years 6 months old, female patient
She was diagnosed with Type 1 DM at 9 months of age (Anti-GAD Antibody positive). Her complaints of diarrhea began at the age of 5 (6-7 times / day, watery). She had been brought to an outer center for chronic diarrhea. In the histopathological examination obtained by upper GIS endoscopy, villus atrophy, crypt hiperplasia, and intraepithelial lymphocytosis were detected. Anti-tissue transglutaminase IgA and Anti-endomisium IgA were negative. Other tests for the etiology of chronic diarrhea were normal. She started a gluten-free diet at the age of 5. Since there was no response to the gluten-free diet. HLA DQ2, and DQ8 tests were negative, the gluten-free diet was discontinued when she was 7years old. During this two-year period of gluten-free diet, steroid treatment had also been tried for refractory celiac, for 6 months. A partial response to steroid treatment was achieved and diarrhea increased after discontinuation. At the age of 8, she had swelling, redness and limitation of movement in one knee and then in both knees, which repeated intermittently. She was thought to have JIA and a NSAID was used.

Keywords

Clinical

References

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