Chronicity of pristane-induced arthritis in rats is controlled by genes on chromosome 14

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×DA)F₂-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 α₁-acid glycoprotein and α₁-microglobulin was found significantly altered in naïve congenic rats compared to the DA rat. The concentration of α ₁-microglobulin was found to be significantly higher throughout the disease course, while α₁-acid glycoprotein had a lower concentration in naïve 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.