Clinical characteristics and response to abatacept of three Mexican patients with LRBA deficiency

Abstract

Abstract Purpose. To describe the genetic and clinical characteristics of three patients with LRBA deficiency, an inborn error or immunity that has not been described previously in Latin American patients. Methods. This study included three pediatric patients with recurrent infections, hypogammaglobulinemia, thrombocytopenia, lymphopenia, and pulmonary and gastrointestinal effects. Exome sequencing was performed, variants in LRBA were confirmed by Sanger sequencing, and segregation was investigated to confirm the occurrence of compound heterozygous variants in two patients. LRBA detection in activated PBMCs was performed for all patients, and immunoglobulin levels and cell populations were determined. Clinical records for patients were consulted to determine the type of infection, lung and colon biopsy results and the response to immunosuppressive treatment, including abatacept. Results. Two of the three patients showed an early onset of manifestations. Two patients carried compound heterozygous genetic variants in LRBA, and one patient carried a homozygous variant. Of the five variants identified, three of them were novel and caused a loss of LRBA expression in two of the patients. The three patients presented lung damage and bowel disease. They showed lymphopenia and/or thrombocytopenia. Biopsy sample analysis showed lung or colon damage, and the colon mucosa showed polymorphonuclear infiltrates. Finally, two patients showed partial remission with abatacept; however, the patient with the largest protein truncation did not respond to abatacept treatment. Conclusion. The variants in LRBA reported in this manuscript are novel or were not previously associated with immunodeficiency. The patients whose cases are reported here showed a variable phenotype. The patient with the worst clinical phenotype had the largest protein truncation.