Juvenile idiopathic arthritis in X-linked agammaglobulinemia with a novel in-frame deletion: a case report and functional analysis

Introduction: X-linked agammaglobulinemia (XLA) is a rare primary humoral immunodeficiency caused by mutation of Bruton tyrosine kinase (BTK), featuring early onset and repeated bacterial infections. Arthritis is an intriguing presentation because despite the constant threat of infection, inflammatory and rheumatic arthritis occur in rare cases, suggesting that unregulated autoimmunity can arise in the context of immunodeficiency. Case presentation: A 17-year-old Chinese male presented with a 4-month course of arthritis in his right knee and right hand. The clinical features and laboratory findings were consistent with juvenile idiopathic arthritis. He had many prior infections and received antibiotic treatment at various local clinics without a definite diagnosis. Immunological studies revealed severely decreased level of serum immunoglobulin and circulating B lymphocytes. Sequencing of the BTK gene in this pedigree identified a novel 3 base pairs deletion in exon 3 resulted in a glutamine deletion, and established the diagnosis of XLA. The patient responded well to oral naproxen and maintained asymptomatic on monthly intravenous immunoglobulin. Conclusions: This case strengthened the importance of early and accurate diagnosis and careful management of XLA patients to maintain the Yin-Yang balance of immunodeficiency and autoimmunity.