Síndrome Linfoproliferativa Autoimune: descrição clínica, laboratorial e genética dos pacientes acompanhados no Serviço de Imunologia do Hospital das Clínicas da UFMG

Abstract

Introduction: Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder caused by a defect in the apoptosis of lymphocytes. Patients usually present in their first decade of life with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, recurring multilineage cytopenias, increased risk of lymphomas and an characteristic expansion of a specific lymphocyte subpopulation called DNT (CD3 + CD4- CD8-). Deleterious germline mutations in the FAS gene are the most common cause of ALPS followed by somatic mutations in the same gene and other genetic changes in FASL, CASP8, CASP10, NRAS, KRAS and PRKCD may be responsible for the minority of cases. There remain those patients who carry undefined genetic defects. Objectives: To describe clinically and genetically and to analyze patients with probable ALPS referred to the Immunodeficiency outpatient clinic at the Federal University of Minas Gerais (UFMG). Methods: This is a descriptive study of a series of cases including six children with probable ALPS, attended at the Immunodeficiency outpatient clinic at UFMG, between 2008 and 2015. The patients clinical data was collected from the medical records and complementary information was gathered through interviews with their families. Results: Among the six patients with probable diagnosis of ALPS, 83.3% (5/6) were male and 100% (6/6) showed the symptoms in the first decade of life (range 18m- 6 years). Lymphoproliferation and autoimmune anemia were the most common clinical manifestations affecting the entire sample and resulted in drug treatment in 83.3% (5/6) of patients. One single child was treated with a splenectomy. Drug treatment to control autoimmune anemia consisted of oral corticosteroids, with complete response in 80% (4/5) of patients, only one child showed a partial response and required the use of corticosteroid-sparing drugs. There was a 40% incidence of lymphoma in children (2/5). Survival in six years was of 83.3% (5/6) of patients. The values of DNT cells were elevated in 83.3% of patients (5/6); the soluble FAS ligand was greater than 200 pg / ml in 40% (2/5) of patients, and serum vitamin B12 showed values of over 1000pg / ml in 60% (3/5) of the sample. The genetic analysis showed variation with clinical significance in FAS in one patient, while five showed no significant variations in the analyzed genes. The study showed incidence of lymphoma in two patients without mutation in FAS, which broadens the spectrum of patients at risk for malignancies. The association of the biomarkers soluble FAS ligand and serum vitamin B12 resulted in a high probability of mutation in FAS in two children in one the significant variation in FAS was identified and in the other there was a high probability of somatic mutation in the same gene. Conclusion: The prognosis of patients with ALPS was good and depends on the proper management of the autoimmune cytopenias. Avoiding a splenectomy and maintaining constant surveillance for early detection of malignancies enables a better quality of life for patients and their families.