Cross-reactivity to proteoglycans in bacterial arthritis: lack of evidence for in vivo role in induction of disease.
Cross-reactivity between bacterial epitopes and cartilage components has been assumed to play a role in the pathology of bacterial-induced arthritis models. In this study, we report prominent proteoglycan (PG) depletion in Safranin-O stained ankle joint sections from collagen-induced arthritic rats. In adjuvant arthritis and streptococcal cell wall-induced arthritis (SCW-A), however, only limited PG degradation was observed. In vitro, PG fractions were able to stimulate T lymphocytes from these arthritic rats. To investigate the contribution of cross-reactivity, Lewis rats were primed with SCW in Freund's incomplete adjuvant (SCW/FIA). This immunization protocol resulted in in vitro stimulatory responses to the SCW antigens and cartilage PG antigens, but not to joint inflammation per se. Next, papain was injected intraarticularly to create a situation in which a large amount of potential cross-reactive cartilage epitopes are released. Interestingly, no inflammatory reaction could be observed in the papain-injected joints of SCW/FIA-primed rats. These data suggest that cross-reactivity between bacterial epitopes and PG does not seem to be a key element in the onset of joint inflammation in bacterial-induced arthritis. However, it cannot be ruled out that at later time points cross-reactivity will contribute to joint inflammation.
van de Langerijt
A G
AG
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Kingston
A E
AE
van Lent
P L
PL
Billingham
M E
ME
van den Berg
W B
WB
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001170:Arthritis, Infectious / Q000276:immunology*; D002356:Cartilage / Q000737:chemistry; D002473:Cell Wall / Q000276:immunology; D003429:Cross Reactions; D000939:Epitopes; D005260:Female; D007114:Immunization; D008213:Lymphocyte Activation; D010206:Papain / Q000494:pharmacology; D011509:Proteoglycans / Q000032:analysis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013291:Streptococcus / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D011509:Proteoglycans; D010206:Papain