A 21-year-old female with a history of recurrent sinus infections, asthma, thrombocytopenia, atrioventricular nodal reentrant tachycardia, and neonatal seizures presented with fever and new-onset status epilepticus. Lumbar puncture demonstrated a lymphocytic pleocytosis with elevated protein. MRI brain showed T2 hyperintensities in the mesial temporal lobe. Infectious etiologies were excluded, and no clinically significant autoantibodies were identified. Treatment included multiple antiseizure medications, ketogenic diet, deep brain simulation and immunotherapies (corticosteroids, intravenous immunoglobulins, plasmapheresis, rituximab, tocilizumab and anakinra). Diagnostic evaluations showed low IgA levels prior to her first dose of rituximab, and she developed pan-hypogammaglobulinemia after rituximab. Genetic testing revealed a pathogenic heterozygous variant in TNFRSF13B c.311G>A (p.Cys104Tyr) which encodes for TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor), a tumor necrosis factor receptor expressed on B cells. Her prolonged hospitalization has been complicated by various infections and posterior reversible encephalopathy syndrome. Currently, she is seizure-free for one month with slow but encouraging signs of neurological recovery.