QUANTITATIVE TRAIT LOCI DISPOSING FOR BOTH EXPERIMENTAL ARTHRITIS ANDENCEPHALOMYELITIS IN THE DA RAT - IMPACT ON SEVERITY OF MYELIN OLIGODENDROCYTE GLYCOPROTEIN-INDUCED EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AND ANTIBODY ISOTYPE PATTERN
I. Dahlman et al., QUANTITATIVE TRAIT LOCI DISPOSING FOR BOTH EXPERIMENTAL ARTHRITIS ANDENCEPHALOMYELITIS IN THE DA RAT - IMPACT ON SEVERITY OF MYELIN OLIGODENDROCYTE GLYCOPROTEIN-INDUCED EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AND ANTIBODY ISOTYPE PATTERN, European Journal of Immunology, 28(7), 1998, pp. 2188-2196
Quantitative trail loci (QTL) controlling inflammatory diseases with d
ifferent organ specificity may hypothetically either be unique for one
disease or shared among different diseases. We have investigated whet
her five non-MHC QTL controlling susceptibility to experimental arthri
tis in the DA rat also influence myelin oligodendrocyte glycoprotein (
MOG)-induced experimental autoimmune encephalomyelitis (EAE) in an F2
intercross between inbred DA and PVG.RT1(a) rats. Two of the five chro
mosome regions affecting arthritis in the DA rat also regulate phenoty
pes of EAE. The DA allele at markers in Cia3 (collagen-induced arthrit
is QTL) on chromosome 4 is associated with more severe EAE and high le
vels 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 o
r 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 cell
s, this QTL may also control Th1/Th2 bias. We conclude that Cia3 and O
ia2 regulate MOG-induced EAE in rats. Furthermore, since both EAE and
arthritis phenotypes co-localize to these gene regions, they may harbo
r genes which are key regulators of pathogenic immune responses.