Sule Haskologlu, Turkey
Ankara University Faculty of Medicine Pediatric Allergy and ImmunologyPresenter of 2 Presentations
CLINICAL SPECTRUM CHANGING FROM ASYMTOPMATIC TO FATAL DISEASE: MHC CLASS I DEFICIENCY
Abstract
Background and Aims
Major histocompability class I deficiency is a rare disease with remarkable clinical and biological heterogeneity. This deficiency consists of a group of autosomal recessive diseases caused by mutations in TAP1, TAP2, tapasin and β2 microglobulin, which are important for intracellular loading of antigens into MHC Class I molecules and stabilizing the complex. The clinical spectrum varies from complete absence of symptoms to life-threatening disease. We aimed to present the clinical, laboratory, genetic and follow-up results of 8 patients who were followed up with MHC Class I deficiency.
Methods
Patients' data were evaluated.retrospectively
Results
8 patients from 4 families (F/M:4/4); median age of 16,5years (range 10-30y), median age of onset of symptoms 3,5years (range 1-17y), median follow up 12,5years (2-15y). We observed bronchiectasia in 7, skin lesions in 4, uveitis in and retinitis in 1 of patients. MHC Class I expresion was measured by flow cytometry very low. The mutation analysis performed and validated by next generation sequencing (NGS) and Sanger’s methods. We detected TAP1 mutation in six patients, TAP2 mutation in two patients. While one of two sibling was almost asymptomatic the other died due to sepsis caused by severe skin lesions. Overall survival is 87.5%.
Conclusions
MHC Class 1 deficiency should be consider in patients with skin lesions, sinopulmonary infections and bronchiectasis. The measure of HLA ABC expression by routine lymphocyte subgroup analysis allows the diagnosis. Clinical manifestation changes from patient to patient. The knowledge about bone marrow transplantation in MHC Class I deficiency is insufficient
RASGRP1 DEFICIENCY PRESENTING WITH HODGKIN LYMPHOMA FOLLOWING BICYTOPENIA
Abstract
Background and Aims
RASGRP1 is a guanine-nucleotide-exchange factor that is involved in lymphocyte development and function. RASGRP1 deficiency was first described as a severe immunodeficiency in 2016. It is characterized by lymphopenia, recurrent infections, autoimmune features, hepatosplenomegaly, lymphadenopathy, EBV-associated lymphoproliferation and B cell lymphoma. Here, we report a patient with RASGRP1 deficiency developing Hodgkin’s Lymphoma following immune cytopenias.
Methods
Case: 8 year-old-boy referred with suspicion of primary immunodeficiency. He was born to consanguineous parents. He had hospitalized due to fever, immune thrombocytopenia and autoimmune hemolytic anemia at 4 years. He treated with glucocorticoids and IVIG. Then he had recurrent fever, otitis media and tonsilitis that require intravenous antibiotic treatments. At 8 years he developed Hodgkin’s Lymphoma. Lymphopenia, positive EBV serology. elevated TCR γδ T cells and decreased follicular T helper cells were detected in the laboratory assessment. Genetic analysis revealed a homozygous homozygous mutation in RASGRP1 gene.
Results
He successfully completed chemotherapy and radiotherapy regimens. He had a sister and we are waiting her genetic results. They are HLA matched siblings.
Conclusions
RASGRP1 deficiency is an immune dysregulation disorder that should be considered in patients with EBV-related lymphoproliferation or malignancy as well as patients with recurrent infections, autoimmune cytopenias and other aoutoimmune diseases. Early diagnosis is important and HSCT can be a curative treatment for patients with RASGRP1 deficiency.