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.
Highlights
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 Autoimmune diseases (ADs)
Analysis of plasma cytokines levels prior to B-cell depletion therapy (BCDT) and six months after RTX treatment of all rheumatic patients showed that IL-6 and IL-8 were significantly elevated in patients prior to RTX compared with controls (Figures 1A and 1B, Table S1)
Our analysis of plasma cytokines before and after BCDT therapy supports the importance of B-cells cytokine secretion in rheumatoid arthritis (RA) and SLEassociated PolyA, and suggests a differential role in each pathology
Summary
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. 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. BAFF (B-cell activating factor, known as B lymphocyte stimulator, BLyS) and APRIL (aproliferation inducing ligand) are some of the most important cytokines influencing development and survival of B-cells, and, in turn, play a major role in ADs pathophysiology [6]. As mentioned, measured plasma cytokines may be produced by several cell populations, which must be considered during the translation of bench results to the bedside
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