To address the possibility that genes specifically control the chronic phase of
arthritis we have isolated a congenic fragment from the resistant E3 rat on the susceptible DA rat background. The isolated fragment covers the Pia6 quantitative trait locus on chromosome 14, which previously has been identified to be linked to chronic
pristane induced
arthritis (PIA) in gene segregation experiments of an (E3 x DA)F(2)-cross. Heterozygous Pia6 congenic rats (DA.Pia6) were protected from chronic active
arthritis specifically, as determined by macroscopic scoring, histopathology and release of
cartilage oligomeric matrix protein (-reflecting ongoing cartilage destruction). The difference was seen only during the chronic active phase of
arthritis starting approximately 5 weeks after onset of
arthritis. Interestingly, the plasma concentration of the
lipocalins alpha(1)-acid glycoprotein and
alpha(1)-microglobulin was found significantly altered in nai;ve congenic rats compared to the DA rat. The concentration of
alpha(1)-microglobulin was found to be significantly higher throughout the disease course, while
alpha(1)-acid glycoprotein had a lower concentration in nai;ve rats, which was highly significant in the chronic phase. The altered concentrations of these
proteins already before development of chronic
arthritis may provide a clue to the pathogenic process controlled by the Pia6 genes. We conclude that the active relapsing chronic
arthritis is under a unique genetic control that is different from the control of acute
arthritis and postulate that the liver plays an important role in this regulation.