IVIg products contain detectable autoantibodies to Ro52, M2, DFS70 and SSA

Abstract

BACKGROUND: Intravenous immunoglobulin (IVIg) is prescribed for immunoglobulin replacement or immunomodulatory therapy. We investigated if IVIg administration could yield false-positive detection of autoantibodies in recipients. METHODS: IVIg from eight lots of four brands (Privigen, Privigen AU, Gamunex, Flebogamma) available in Australia, were assayed by line blot immunoassay (Euroimmun, Germany) for presence of IgG against extractable nuclear antigens (ENA), myositis, liver, and neuronal-associated antigens, and IgM against gangliosides. RESULTS: At 10 g/L, all IVIg products contained detectable antibodies to Ro52 (band intensity [BI]:15-61), M2 (BI:12-33), DFS70 (BI:14-25) and SSA (BI:12-20). Flebogamma contained considerably less autoantibodies than the other three brands. No IVIg product had measurable antibodies to antigens in neuronal, liver, gangliosides, and myositis blots except Ro52. Antibodies to Ro52 and M2 were detectable as low as 2.5 g/L of titrated Privigen. Sera spiked with IVIg showed falsely elevated BI across antibodies to all antigens, except PL-7, Ku and dsDNA with BI decrease from 35 to 21, 45 to 34 and 82 to 47 respectively. CONCLUSIONS: IVIg can cause false-positive autoantibody detection. Of the autoantibodies assessed, Ro52, followed by M2, DFS70 and SSA were the most frequently targeted. The level of detectable autoantibodies increases with higher dose. Clinician awareness is necessary to avoid misinterpretation of the significance of detection of autoantibodies in patients treated with IVIg.