Incorporating robustness and an evaluation of independent mechanisms into studies evaluating virus reduction in a new IGIV product manufactured by a chromatography-based process

5 0 ~ Selective IgA Deficiency Associated With a Non-PR-3, Positive ~JIl~ C-ANCA Nancy Wasserbauer*, Robert W Hostoffer§ *Midwestern University, Highland Heights, OH §Case Western Reserve University, Highland Hts, OH Selective IgA deficiency is associated with multiple serologic autoantibodies and multiple autoimmune disorders such as hemolytic anemia, rheumatoid arthritis, and systemic lupus erythematosus. We report a patient with IgA deficiency, a positive C-ANCA, and a negative PR-3. RM is a 55year-old white female who presented for the evaluation of IgA deficiency, positive ANA, hemolytic anemia, and recurrent infections. The patient initially sought care for a bladder infection and submental lymphadenitis. She subsequently developed a Coombs positive hemolytic anemia. A C T scan revealed splenomegaly. Additional CT scans of the chest and sinuses were unremarkable except for a left maxillary sinus cyst. Lab studies revealed a positive C-ANCA, negative PR-3, positive mild proteinurea at 210 mg/L. Serum immunoglobulins revealed an absence of IgA, but an elevated IgG at 2681 mg/dl (620-1400 mg/dl). The IgM was normal. IgG subclasses revealed an increase in IgGl at 2038 mg/dl (450-1400 mg/dl). Serum immunoelectrophoresis showed an elevated gammaglobulin at 41.9 (0.012.5 mg/L) with no monoclonal spikes. Urine immunoelectrophoresis showed an increase in the alpha-1 at 36.7 mg/L (0.0-11.1 mg/L), alph-2 at 70.2 mg/L (0.9-14.1 mg/L), betaglobulin 28.6 mg/L (0.0-15.9 rag/L) and gammaglobulin at 41.9 mg/L (0.0-12.5 mg.L), suggestive of glomerular and tubular proteinuria. The ESR was high at 29 (0-20). CBC showed a depressed total leukocyte count due to a decreased lymphocyte count at 670 g/L (1200-4800 g/L). C3, C4 and CH50 were normal and her rheumatoid factor was normal. These urine results were transient and a subsequent nephrology consultation revealed an absence of renal involvement. A positive C-ANCA represents a family of cytoplasmic staining antibodies which includes anti-PR-3. We report the first case of IgA deficiency with a positive C-ANCA, a negative PR-3 and no evidence of vasculitis.