B cell depletion treatment decreases CD4+IL4+ and CD4+CD40L+ T cells in patients with systemic sclerosis

Rheumatol Int. 2019 Nov;39(11):1889-1898. doi: 10.1007/s00296-019-04350-4. Epub 2019 Jun 21.

Abstract

Recent data suggests that rituximab may favorably affect skin fibrosis and lung function in patients with systemic sclerosis. Based on experimental data suggesting a key role of B and T cells in scleroderma we aimed to explore the effect(s) of rituximab treatment on T cell subpopulations. Fifteen patients with scleroderma who received rituximab treatment and six who received standard treatment alone were recruited. Peripheral CD4+IL4+, CD4+INFγ+, CD4+IL17+ and CD4+CD40L+ T cells were assessed using flow cytometry. Using ELISA, serum levels of IL4 were assessed. Skin CD4+IL4+ T cells were assessed with confocal microscopy from skin biopsies. Following rituximab treatment skin CD4+IL4+ T cells obviously decreased as seen with confocal microscopy. Moreover, peripheral CD4+IL4+ T cells decreased significantly compared to those from patients who received standard treatment alone: median (IQR): 14.9 (22.63-12.88) vs 7.87 (12.81-4.9)%, p = 0.005 and 9.43 (19.53-7.50)% vs 14.86 (21.96-6.75)%, p = NS at baseline and 6 months later respectively, whereas there was no difference in serum IL4 levels. Peripheral CD4+CD40L+ T cells also decreased significantly following rituximab treatment compared to those from patients who received standard treatment alone: median (IQR): 17.78 (25.64-14.44)% vs 8.15 (22.85-3.08)%, p = 0.04 and 22.13 (58.77-8.20)% vs 72.11 (73.05-20.45)%, p = NS at baseline and 6 months later respectively. Furthermore, peripheral CD4+INFγ+ and CD4+IL17+ T cells revealed no differences following rituximab treatment. Our study demonstrates a link between rituximab treatment and CD4+IL4+ T cell decrease both in the skin and peripheral blood of patients with SSc.

Keywords: B cells; Lymphocytes; Rituximab; Scleroderma; T cells.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes / immunology*
  • CD40 Ligand
  • Female
  • Humans
  • Immunologic Factors / therapeutic use*
  • Interleukin-4 / blood*
  • Male
  • Middle Aged
  • Rituximab / therapeutic use*
  • Scleroderma, Systemic / blood
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / immunology
  • Treatment Outcome

Substances

  • Immunologic Factors
  • CD40 Ligand
  • Interleukin-4
  • Rituximab