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Targeting activated T cells: successful use of anti-CD25 monoclonal antibody basiliximab in a patient with systemic sclerosis
  1. H U Scherer,
  2. G-R Burmester,
  3. G Riemekasten
  1. Department of Rheumatology and Clinical Immunology, Charité—University Medicine Berlin, Berlin, Germany
  1. Correspondence to:
    H U Scherer
    Department of Rheumatology and Clinical Immunology, Charité—University Medicine Berlin, Schumannstrasse 20-21, 10117 Berlin, Germany; ulrich.scherer{at}charite.de

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Serum levels of soluble interleukin (IL) 2 receptor strongly correlate with skin involvement, disease progression and mortality in systemic sclerosis (SSc).1,2 This finding underlines the role of activated and possibly dysregulated T cells in the pathogenesis of the disease. Specifically targeting these cells may therefore be a new therapeutic approach. Basiliximab is a chimeric monoclonal antibody directed against the α chain (CD25) of the IL2 receptor.3 It is approved for the treatment of kidney allograft rejections. Here, we describe the successful use of basiliximab in combination with cyclophosphamide in a patient with severe, rapidly progressive SSc.

In February 2004, a 43-year-old woman with a 3-year history of Scl-70-positive, diffuse SSc presented to our department. Despite prior treatment with methotrexate, prostacycline infusions, azathioprine and calcium channel blockers, the patient presented with severe Raynaud’s phenomenon, digital ulcers (fig 1A) and progressive skin thickening. Polymorphic ventricular premature complexes, tricuspidal regurgitation of IV° (no coaptation of flags), dyspnoea at rest and pericardial effusion (30 mm) suggested cardiac involvement. Pulmonary artery pressure as assessed by right-heart catheterisation was normal. A high-resolution computed tomography scan showed mild basal “ground-glass” opacification indicative of interstitial lung disease (<10%). Table 1 summarises additional findings.

Table 1

 Selected laboratory and diagnostic findings and their change over time during treatment with basiliximab

Figure 1

 Regression of skin ulcers during therapy with basiliximab (A) before start of treatment, (B) after 6 months of treatment and (C) further improvement and prolonged effect after the end of basiliximab treatment. Mod., modified.

Faced by rapid disease progression with predominant cardiac and skin involvement despite conventional treatment, we started treatment with intravenous pulse cyclophosphamide (CYC, 1 g/month), prednisolone (initial dose 75 mg/day, reduced to 10 mg/day in June), angiotensin-converting enzyme inhibitor, prostacycline infusions (5-10 days a month) and, with a delay of 3 weeks, basiliximab as additional selective immunosuppressant. Alternative options such as oral CYC or high-dose glucocorticoids were discussed but deemed hazardous as they implied the risk of renal crisis or serious infections. Basiliximab (20 mg) was given twice in weekly intervals, followed by an infusion at day 28 and at monthly intervals thereafter. In total, basiliximab was given for 6 months. Thereafter, only CYC, prostacycline and low-dose prednisolone were continued.

Therapeutic efficacy was most prominent with regard to skin involvement (fig 1B). Modified Rodnan Skin Score reduced from 24 to 19 in 6 months, with a further reduction to 11 at month 9 (fig 1C). Cardiac involvement also reduced (table 1), but the structural damage remained. Lung involvement showed improvement in corrected carbon monoxide diffusion capacity, but forced vital capacity worsened.

Activated T cells have been associated with skin involvement and disease activity in SSc.1,2 Soluble IL2 receptor, large numbers of CD69 or CD3 infiltrating T cells and oligoclonal expansion of T cells suggesting antigen-specific activation have been found in scleroderma skin lesions.4–6 T cells are thought to be activated early during disease development, leading to fibroblast activation through cytokine secretion and cell-to-cell contact. Considering these observations, rapid disease progression and short overall disease duration in our patient, we decided to intensify treatment by selectively targeting activated T cells with anti-CD25 monoclonal antibody basiliximab. It is impossible to attribute aspects of efficacy solely to basiliximab in this setting of combination treatment. Excellent, rapid and sustained improvement in skin involvement, however, exceeded our expectations, which were based on published data.

Combination regimen comprising intravenous pulse CYC and prednisolone have mostly been evaluated with regard to SSc-related interstitial lung disease.7–9 Albeit methodological differences, small but consistent improvements in pulmonary function tests have been reported by various authors, generally in 6 months of treatment.9 Improvement of skin involvement has rarely been assessed, including one study reporting a mean reduction in modified Rodnan Skin Score of 4.9 after 6 months and 5.4 after 12 months.7 More prominent effects have been described in patients with early SSc treated with oral CYC.10

The case presented points towards a beneficial effect of targeting activated T cells in skin invlovement in SSc, especially early in the course of disease.

Acknowledgments

GR acknowledges financial support from the German Network for Systemic Sclerosis (Bundesministerium für Bildung und Forschung (BMBF)) and from the EUSTAR (EULAR) programme.

REFERENCES

Footnotes

  • Competing interests: None declared.