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) could 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 month, followed by 0.5 mg daily for 11 months. Peripheral blood mononuclear cells (PBMC) were obtained from the patients and cultured with human alpha1(I) and alpha2(I) chains, before and after CI treatment. Culture supernatants were analyzed for levels of interferon-gamma (IFNgamma) and interleukin-10 (IL-10). Sera obtained before and after treatment were analyzed for levels 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 reductions in levels of IFNgamma and IL-10 in alpha1(I)- and alpha2(I)-stimulated PBMC culture supernatants, indicating that T cell immunity to CI was decreased by this treatment. Serum levels of sIL-2R also decreased significantly after oral CI treatment, suggesting a reduction in T cell activation. Significant improvements occurred in the modified Rodnan skin thickness score and the modified Health Assessment Questionnaire after 12 months of oral CI in this open trial. The lung carbon monoxide diffusing capacity improved statistically and showed a trend toward clinically significant improvement.


CONCLUSIONS
Oral administration of bovine CI to patients with diffuse or limited 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 oral tolerance to CI in patients with SSc is justified to determine whether it has therapeutic efficacy.
McKown
K M
KM
Department of Veterans Affairs Medical Center, University of Tennessee, Memphis, USA.
Carbone
L D
LD
Bustillo
J
J
Seyer
J M
JM
Kang
A H
AH
Postlethwaite
A E
AE
D000284:Administration, Oral; D000818:Animals; D002417:Cattle; D003094:Collagen / Q000008:administration & dosage / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D012595:Scleroderma, Systemic / Q000276:immunology*
D007371:Interferon-gamma; D003094:Collagen