Background
LPS Responsive Beige like Anchor Protein (LRBA) is a BEACH Domain Containing Protein that was first fully cloned in mouse and human in 2001. LRBA mRNA is expressed in almost all cell types with an elevated expression in immune cells. LRBA deficient patients have inadequate proliferation of B cells and defective autophagy resulting in hypogammaglobulinemia and autoimmunity. Here we present the first Indian cohort of LRBA deficiency.
Clinical and immunological phenotype, therapeutic approach and outcome of 3 patients from 3 different families were assessed retrospectively in this study.
Demographics: Age of first symptom varied from 10 months for homozygous mutation to average of 4 years for the heterozygous one. All patients had autoimmune cytopenias with age of onset around 3 years of age.Clinical phenotype: The most common clinical manifestations was organomegaly and autoimmunity. Autoimmunity mainly presented as immune mediated cytopenia. One child had family history of autoimmunity. One patient had insulin dependent diabetes mellitus with celiac disease.Infectious profile: All patients had at least one documented infectious episode. 2 episodes of viral infections were seen, EBV and severe chickenpox.Immunological phenotype:The only non-immunosuppressed patient had a normal lymphocyte subset analysis. All 3 patients had a normal immunoglobulin assay at presentation, one child developed hypogammaglobulinemia after rituximab. Therapeutic Approach:As abatacept is too costly and non-affordable in our patient cohort we used sirolimus for all 3 patients. All children have no side effects to sirolimus therapy so far. None of them have undergone HSCT.
Sirolimus can be effective as single drug with good disease control in LRBA deficiency.