Introduction: This report highlights a rare case of genetic LRBA deficiency, resulting in autoimmunity and humoral immunodeficiency, and discusses targeted treatment with abatacept, a CTLA4-immunoglobulin fusion drug. [1]
Case Description: A 21-year-old Lebanese male had a history of hypogammaglobulinaemia, autoimmune cytopaenias, juvenile idiopathic arthritis, uveitis, alopecia and enteropathy with recurrent infections and weight loss. Treatment had included corticosteroids, intravenous immunoglobulin, methotrexate and adalimumab with recent change to tofacitinib. Due to a family history of consanguinity and autoimmunity, genetic testing was performed. This revealed a biallelic loss-of-function mutation in the gene LRBA, encoding the LRBA (lipopolysaccharide-responsive beige-like anchor) protein. The same mutation was also identified in his brother, who presented with humoral immunodeficiency, autoimmunity and non-malignant lymphoproliferation. Tofacitinib was ceased and abatacept IV was commenced.
Discussion: The LRBA protein plays an important role in the expression, function and trafficking of CTLA-4 (cytotoxic T lymphocyte antigen-4), a potent inhibitory immune receptor. [1] Loss of function mutations in the LRBA gene encoding the LRBA protein cause a reduction in the surface expression of CTLA-4. There is a variable clinical phenotype, which can include immune dysregulation and autoimmunity, lymphoproliferation, recurrent infections with parenchymal lung damage, hypogammaglobulinaemia and failure to thrive. [2] There may be reduced T regulatory cell counts and B-cell subset counts, particularly in switched memory B cells and plasmablasts. [2] This case explores targeted treatment with abatacept, a CTLA4-immunoglobulin fusion drug. [1] Other treatment modalities have included corticosteroids, intravenous immunoglobulin, mycophenolate mofetil, tacrolimus/sirolimus, hydroxychloroquine and haematopoietic stem cell transplantation. [2] This case also highlights links with immune-related adverse events of immune checkpoint inhibition for cancer therapy. [3]