Induction of immune tolerance to human type I collagen in patients with systemic sclerosis by oral administration of bovine type I collagen

Objective. To determine whether oral tolerance to type I collagen (CI) coul d be induced in patients with systemic sclerosis (SSc). Methods. Twenty adult patients with limited or diffuse SSc were enrolled in a study to receive 0.1 mg of solubilized native bovine CI daily for 1 mont h, followed by 0.5 mg daily for 11 months. Peripheral blood mononuclear cel ls (PBMC) were obtained from the patients and cultured with human alpha 1(I ) and alpha 2(I) chains, before and after CI treatment. Culture supernatant s were analyzed for levels of interferon-gamma (IFN gamma) and interleukin- 10 (IL-10). Sera obtained before and after treatment were analyzed for leve ls of soluble IL-2 receptor (sIL-2R). Although this study was not intended to assess the clinical efficacy of oral CI administration in SSc, selected measures of disease severity and organ involvement were evaluated. Results. Oral administration of CI to SSc patients induced significant redu ctions in levels of IFN gamma and IL-10 in alpha 1(I)- and alpha 2(I)-stimu lated PBMC culture supernatants, indicating that T cell immunity to CI was decreased by this treatment. Serum levels of sIL-2R also decreased signific antly after oral CI treatment, suggesting a reduction in T cell activation. Significant improvements occurred in the modified Rodnan skin thickness sc ore and the modified Health Assessment Questionnaire after 12 months of ora l CI in this open trial. The lung carbon monoxide diffusing capacity improv ed statistically and showed a trend toward clinically significant improveme nt. Conclusion. Oral administration of bovine CI to patients with diffuse or li mited SSc induces a reduction in T cell reactivity to human CI, appears to be well tolerated, and does not worsen the disease. Further evaluation of o ral tolerance to CI in patients with SSc is justified to determine whether it has therapeutic efficacy.