Km. Mckown et al., Induction of immune tolerance to human type I collagen in patients with systemic sclerosis by oral administration of bovine type I collagen, ARTH RHEUM, 43(5), 2000, pp. 1054-1061
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.