Sugar-free, glycine-stabilized intravenous immunoglobulin prevents skin but not renal disease in the MRL/lpr mouse model of systemic lupus

Abstract

Intravenous immunoglobulin (IVIG) has a therapeutic potential in many autoimmune diseases. Based on its immune modulating and complement inhibiting effects, IVIG has been tested in systemic lupus erythematosus (SLE), but due to osmotic tubular injury caused by immunoglobulin-stabilizing sugar components, lupus nephritis had been accelerated in some patients, thus IVIG use in SLE has been abandoned. The availability of non-sugar-stabilized IVIG raised the possible re-evaluation of IVIG for SLE. We investigated high-dose, long-term non-sugar-stabilized IVIG treatment on skin and renal SLE manifestations in the MRL/lpr mouse model. Animals were treated once a week with glycine-stabilized IVIG or saline (0.2 ml/ 10 g BW) from 6 weeks until they were humanely killed at 5 months of age. IVIG diminished macroscopic cutaneous lupus compared with saline treated mice. Histology and complement-3 immunostaining also demonstrated a significant reduction of skin disease after IVIG treatment. However, renal histology and function were similar in both groups. Compared with typical osmotic tubular damage induced by 5% sucrose and 10% maltose (used for IVIG stabilization), we did not observe any osmotic tubular injury in the glycine-stabilized IVIG treated mice. Our data demonstrate a beneficial effect of IVIG on skin lupus without renal side-effects. Deeper understanding of the organ-specific pathomechanism may aid an individualized SLE therapy.