Susceptibility of DA rats to arthritis induced with adjuvant oil or rat collagen is determined by genes both within and outside the major histocompatibility complex.
Inbred DA rats are remarkably susceptible to arthritis induced both by non-immunogenic mineral oil only (OIA) and by rat collagen II together with mineral oil (rCIA). This fact enables interesting studies concerning which DA genes are associated with the arthritogenicity of adjuvant oil and collagen, respectively. In this paper the authors have investigated the role of genes within and outside the major histocompatibility complex (MHC), in this respect by comparative susceptibility studies in inbred rat strains (DA, LEW) and MHC-congenic strains (DA.1I, DA.1O, DA.1M, DA.1H, LEW.1AV1, PVG.1AV1). The authors confirm earlier reports on the arthritis-promoting nature of the DA MHC haplotype (RT1av1), but demonstrate that neither OIA nor rCIA is restricted to this haplotype or its class II alleles (Ba, Da). A decisive role of non-MHC genes in determining susceptibility is also clear since the PVG.1AV1 strain, with the permissive RT1av1 haplotype, is resistant to both arthritis models. In conclusion, the authors demonstrate that the susceptibility of DA rats to OIA and rCIA is determined similarly, by permissive genes both within and outside the MHC. Second, and more interesting from a general perspective, the investigation demonstrates a notable influence of genes within and outside the MHC on the pathogenic capacity of a non-immunogenic adjuvant oil. This adjuvant is in turn a critical component in provocations leading not only to rCIA but also to many other experimental autoimmune diseases where the influence of 'adjuvant response genes' is rarely considered.
Lorentzen
J C
JC
Department of Medicine, Karolinska Institute, Stockholm, Sweden.
Klareskog
L
L
D000818:Animals; D001168:Arthritis / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D001169:Arthritis, Experimental / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D003094:Collagen / Q000494:pharmacology*; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology*; D020022:Genetic Predisposition to Disease; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics
D003094:Collagen; D005620:Freund's Adjuvant