Comparison of Plasma Cytokine Levels before and after Treatment with Rituximab in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus-Associated Polyautoimmunity

Abstract

Introduction: Coexistence of more than one autoimmune disease (AD) in a single patient is known as polyautoimmunity, and may be seen in up to 35% of patients with ADs. The elimination of B-cells using Rituximab (RTX) improves clinical status in different ADs. The role of cytokine production by B-cells is unclear in systemic lupus erythematosus (SLE) and polyautoimmunity. Methods: As an exploratory study, plasma from 11 patients with either rheumatoid arthritis (RA) or SLE-associated polyautoimmunity was assessed prior and 6 months after therapy with RTX. Eight healthy individuals were used as controls. Cytokine levels were measured using ELISA (IFN-α and TGF-β1) or Cytometric Bead Array (TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12p70). Results: Prior to RTX, IL-6 was only elevated in RA and IL-8 was elevated in both RA and SLE-associated polyautoimmunity, compared with controls. After RTX, significant decreases of IL-6 in RA and IL-8 in SLE-associated polyautoimmunity were observed. Levels of other cytokines measured were either similar (IFN-α, TGF β1) or below the detection limit (TNF-α, IL-1β, IL-10, IL-12p70) for both patients and controls. Conclusion:Our data highlight the importance of B-cell cytokine secretion in RA and SLE-associated polyautoimmunity, and suggest a differential role in each pathology. A significant increase of IL-8 prior to RTX in both groups, and a significant decrease after therapy only in SLE-associated polyautoimmunity support the potential of IL-8 as a therapeutic target. The heterogeneity of the polyautoimmunity patient population highlights the importance of the selection of specific subsets in future research.