Complement C2 deficiency disarranging innate and adaptive humoral immune responses in a pediatric patient: Treatment with rituximab

Introduction Complement deficiencies (CDs) are classified as primary immunodeficiency disorders (PIDs) because diminished opsonization or the inability to form the membrane attack complex increases the susceptibility to pyogenic bacterial infections (1). Moreover, diverse autoimmune manifestations occur that vary with the particular CD (1–3). Complement C2 deficiency (C2D; MIM217000) is classically associated with early-onset invasive pneumococcal infections and systemic lupus erythematosus (SLE) or SLE-like manifestations, which typically present in early or middle adulthood (3,4). Due to its low prevalence ( 1:20,000) (4) and variable clinical manifestations, publications on the treatment of C2D are scarce. In this case report, we describe a C2D patient with the earliest onset of SLE published, to our best knowledge, thus far. We report on rare complications such as immune complex–mediated leukocytoclastic vasculitis (LCV), destructive follicular bronchiolitis (DFB) with polyclonal B cell proliferation, and disturbed humoral immune responses, including dysgammaglobulinemia and specific antibody deficiency, therefore defining a novel phenotype. Providing a detailed histologic, immunologic, and genetic workup, we discuss the pathophysiology of C2D as a complex disorder at the interface between innate and adaptive humoral immunity. Finally, we describe, for the first time, the effective treatment with rituximab (RTX), implicating B cell depletion as a therapeutic strategy for the autoimmune manifestations of the PID.