Induction of tolerance with intranasal administration of human cartilage gp-39 in DBA/1 mice: amelioration of clinical, histologic, and radiologic signs of type II collagen-induced arthritis.
OBJECTIVE
Human cartilage glycoprotein 39 (HC gp-39) was recently identified as a candidate autoantigen in the pathogenesis of rheumatoid arthritis. In the present studies, we investigated the capacity of HC gp-39 to interfere in clinical disease induced by an unrelated autoantigen, type II collagen (CII), by the induction of cross-tolerance.


METHODS
DBA-1j/Bom mice were immunized with bovine CII/complete Freund's adjuvant and were given intraperitoneal booster injections of CII on day 21. Tolerance was induced via the intranasal pathway with either the disease-inducing antigen (CII), a control antigen (ovalbumin), or HC gp-39 either before priming with CII or near the day of the booster injection. Arthritis was monitored visually, and joint pathology was examined histologically and radiologically. In addition, CII antibody levels in serum were analyzed by enzyme-linked immunosorbent assay.


RESULTS
In contrast to treatment before priming, intranasal application of HC gp-39 after immunization markedly suppressed disease activity and prevented joint destruction, whereas application of ovalbumin or CII was ineffective. Interference of HC gp-39 with the immune response to CII was demonstrated by decreased anti-CII antibody levels. The combined data indicate that intranasal treatment with HC gp-39 may trigger modulatory or regulatory mechanisms that interfere with the expression of disease in murine collagen-induced arthritis.


CONCLUSIONS
HC gp-39 is the first cross-tolerance-inducing protein in arthritis that down-modulates a spectrum of disease features when given in a semitherapeutic protocol.
Joosten
L A
LA
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Coenen-de Roo
C J
CJ
Helsen
M M
MM
Lubberts
E
E
Boots
A M
AM
van den Berg
W B
WB
Miltenburg
A M
AM
D054392:Adipokines; D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000187:drug effects / Q000378:metabolism; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy*; D000071451:Chitinase-3-Like Protein 1; D003094:Collagen / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects; D004361:Drug Tolerance; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007596:Joints / Q000473:pathology; D037102:Lectins; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA
D054392:Adipokines; D000906:Antibodies; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D003094:Collagen