Work

Using Helper T Cell Function to Predict the Response of Chronic GVHD Patients to ECP Therapy

Year: 2017

Type: article

Abstract: Chronic graft-versus host disease (GvHD) affects approximately 30-70% of patients undergoing hematopoietic stem cell transplantation. Extracorporeal photopheresis (ECP) therapy has emerged as a promising second-line therapy for patients with steroid-refractory chronic GvHD. However, ECP is only successful in 50-80% of these patients and there is considerable delay between the onset of ECP therapy and clinical improvement in symptoms. Thus, a method to predict which patients might benefit from ECP would be highly valuable. To determine whether CD4+ T cell differentiation might serve as a predictor, CD4+ T cells were isolated from ten steroid-resistant GvHD patients prior to the initiation of ECP therapy. Patients (Table 1) underwent ECP therapy two times per week for four weeks and then two times per week every other week. CGVHD was scored using NIH criteria (Table 2). CD4+ T cells were purified via negative selection and were stimulated with plate-bound anti-CD3 10 mg/ml and anti-CD28 5 mg/ml for five days. Tissue culture supernatants were collected and stored at −80°C until analysis, Data were collected using a Luminex 200 and analyzed using MILLIPLEX® Analyst software (Millipore).The production of 42 cytokines and chemokines were measured in the tissue culture supernatant and compared to the change in GvHD NIH score over a six-month period.Table 1Patient demographics.Table 2The immunosuppressive agents are shown for each patient. In addition, the NIH score and prednisone dose at baseline and 6 months are shown, as well as any immunosuppressive drugs added during the study.Table 2The immunosuppressive agents are shown for each patient. In addition, the NIH score and prednisone dose at baseline and 6 months are shown, as well as any immunosuppressive drugs added during the study. The scatter plots for change in NIH versus cytokine are presented in Figure 1. In scatter plots, a linear regression line along with 95% confidence band are fitted to data. The linear regression line provides prediction for change in NIH score based on the cytokine values. The cytokines that correlated most strongly with the change in NIH score included a mixture of Th1, Th2, and Th9 cytokines. In addition, a principal component analysis showed that five principal components accounted for 90% of the variation. The results of our small pilot study suggest that cytokine production by CD4+ T cells may be a useful prognostic indicator of successful ECP therapy in steroid-resistant chronic GvHD patients.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2016.12.305