Quantitative trait loci disposing for both experimental arthritis and encephalomyelitis in the DA rat; impact on severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis and antibody isotype pattern.
Quantitative trait loci (QTL) controlling inflammatory diseases with different organ specificity may hypothetically either be unique for one disease or shared among different diseases. We have investigated whether five non-MHC QTL controlling susceptibility to experimental arthritis in the DA rat also influence myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in an F2 intercross between inbred DA and PVG.RT1a rats. Two of the five chromosome regions affecting arthritis in the DA rat also regulate phenotypes of EAE. The DA allele at markers in Cia3 (collagen-induced arthritis QTL) on chromosome 4 is associated with more severe EAE and high levels of anti-MOG antibodies of the IgG2c subclass. Since production of antibodies of the IgG2c subclass may be stimulated by Th1 cells, and there is previous evidence that such cells promote EAE, it is possible that both of the studied phenotypes are controlled by the same gene or genes regulating Th1/Th2 cell differentiation. Furthermore, we show that Oia2 (oil-induced arthritis QTL) on chromosome 4 regulates levels of anti-MOG antibodies of the IgG1 subclass and of anti-MOG IgE, but that this gene region does not affect clinical disease severity in our study. Since production of IgE and IgG1 may be stimulated by Th2 cells, this QTL may also control Th1/Th2 bias. We conclude that Cia3 and Oia2 regulate MOG-induced EAE in rats. Furthermore, since both EAE and arthritis phenotypes co-localize to these gene regions, they may harbor genes which are key regulators of pathogenic immune responses.
Department of Medicine, Karolinska Hospital, Stockholm, Sweden. Ingrid.Dahlman@cmm.ki.se
I
I
Dahlman
J C
JC
Lorentzen
K L
KL
de Graaf
A
A
Stefferl
C
C
Linington
H
H
Luthman
T
T
Olsson
D000818:Animals; D001168:Arthritis / Q000235:genetics*; D002874:Chromosome Mapping; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007132:Immunoglobulin Isotypes / Q000032:analysis*; D007371:Interferon-gamma / Q000502:physiology; D008297:Male; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D019655:Quantitative Trait, Heritable; D051381:Rats; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D007371:Interferon-gamma