Bruton's Tyrosine Kinase Is Essential for Human B Cell Tolerance

Most polyreactive and antinuclear antibodies are removed from the human antibody repertoire during B cell development. To elucidate how B cell receptor (BCR) signaling may regulate human B cell tolerance, we tested the specificity of recombinant antibodies from single peripheral B cells isolated from patients suffering from X-linked agammaglobulinemia (XLA). These patients carry mutations in the Bruton's tyrosine kinase (BTK) gene that encode an essential BCR signaling component. We find that in the absence of Btk, peripheral B cells show a distinct antibody repertoire consistent with extensive secondary V(D)J recombination. Nevertheless, XLA B cells are enriched in autoreactive clones. Our results demonstrate that Btk is essential in regulating thresholds for human B cell tolerance

Central retinal artery occlusion secondary to Barlow's disease

Purpose: To report a rare case of isolated, unilateral CRAO in a young patient with mitral valve prolapse secondary to Barlow's disease. Observations: A 29-year-old woman with history of premature ventricular contractions and cardiac ablation presented to the emergency room after sudden onset painless visual loss in her left eye (OS). Her vision was 20/20 in her right eye and hand motion in the left. Fundus exam demonstrated a central retinal artery occlusion (CRAO) OS. Computerized tomography of head and neck were unremarkable. She underwent cerebral angiogram and local intra-arterial thrombolysis. Her vision remained stable post-procedure, with marked APD and stable fundus examination. Her cardiac work-up revealed a left atrial mass with calcified mitral valve, and small atrial septal defect. Rheumatologic, hematologic, and auto-immune work-up were unremarkable. She underwent resection of the mass with repair of mitral valve and ASD closure. Surgical pathology was compatible with diagnosis of Barlow's disease, a cause of mitral valve prolapse. The patient underwent intravitreal injection of anti-VEGF therapy at one month follow-up, with vision stable at hand motion and without neovascularization on subsequent evaluation. Conclusions: In young patients presenting with CRAO, aggressive work-up for systemic disease or embolic source must be undertaken to avoid future sequelae. Keywords: Central retinal artery occlusion, Barlow's disease, Mitral valve prolapse, Intra-arterial thrombolysis, Tissue plasminogen activator, tP

Daratumumab-induced transient myopic shift

Purpose: To describe an unprecedented case of transient myopic shift induced by a chemotherapeutic agent, daratumumab. Observations: A 43-year-old emmetropic female with multiple myeloma experienced sudden onset of myopic shift during her first intravenous dose of daratumumab, an increasingly common FDA-approved chemotherapeutic agent. Her myopia was corrected with -4D lenses in both eyes, and the patient reports cessation of symptoms and disuse of lenses after two days. Conclusions and importance: A number of medications have been documented to induce transitory myopic shift, and this report now includes daratumumab among such agents. Further clinical findings regarding the mechanism and frequency of daratumumab-induced myopic shift are needed to further develop our understanding of its tangential effect on the eye. Keywords: Transient myopia, Myopic shift, Multiple myeloma, Daratumuma