B-cell driven autoimmunity in two patients with monogenic autoinflammatory disorders

Autoimmunity and autoinflammation are classically recognized as two different disease processes. In this report, we present two patients with Behcet’s disease (BD)-like autoinflammation who subsequently developed lupus-like serology and B-cell phenotypes. A retrospective review of medical records and research-based flow cytometry of two patients with the monogenetic autoinflammatory disease was performed. Our first patient had a history of multiple skin and genital lesions, as well as persistent cough with pulmonary nodules. Her immune evaluation demonstrated marked CD4 activation with decreased naïve CD4 cells. Throughout her disease course, she developed high titer ANA and dsDNA. Her genetic analysis revealed a heterozygous c.1039C>T (p. Gln347*) variant of the RELA gene, a truncation mutation. The downstream truncated variant of the RELA gene has been reported to be associated with BD-like autoinflammatory syndrome. Our second patient had a BD-like presentation with recurrent mouth and vaginal ulcers, Crohn’s disease-like GI inflammation, and periodic fevers. She also had features of autoimmune disease with Hashimoto thyroiditis. At disease onset, she was negative for ANA. However, over a period of eight years, her ANA titers increased to >1:2560, with high titer anti-chromatin antibody and new-onset bilateral sacroiliitis. Her genetic testing revealed a (p.Arg364Lysfs*25) variant of the TNFAIP3 gene associated with BD-like autoinflammatory syndrome. Research-based B-cell profiles in both patients revealed increased B-cell autoreactivity and B-cell dysregulation similar to classical lupus patients. Our case report demonstrated that the monogenetic autoinflammatory disease process could evolve to develop autoimmunity, thus complicating clinical presentation and management.