Collagen-Induced Arthritis is Exacerbated in C-Reactive Protein Deficient Mice

Objective—Blood C-Reactive Protein (CRP) is routinely measured to gauge inflammation and in rheumatoid arthritis (RA), heightened CRP is predictive of a poor outcome and lowered CRP indicative of a positive response to therapy. CRP interacts with the innate and adaptive immune systems in ways that suggest it may be causal in RA and, although this is not proven, it is widely assumed CRP makes a detrimental contribution to the disease process. Paradoxically, animal studies indicate CRP might be beneficial in RA. Methods—We compared the impact of CRP deficiency versus transgenic over-expression on the inflammatory and immune responses using CRP deficient mice (Crp−/−) versus human CRP transgenic mice (CRPTg), respectively, and we compared the susceptibility of wild type, Crp −/− , and CRPtg to collagen-induced arthritis (CIA), a disease that resembles RA in humans. Results—CRP deficiency significantly altered the inflammatory cytokine response evoked by challenge with endotoxin or anti-CD3 antibody, and heightened some immune responses. Compared to CIA in wild type mice, CIA in Crp −/− progressed more rapidly and was more severe whereas CIA in CRPTg was dramatically attenuated. Despite these disparate clinical outcomes, anti-collagen autoantibody responses during CIA did not differ among the genotypes. Conclusion—CRP exerts an early and beneficial effect in mice with CIA. The mechanism of this effect remains unknown but does not involve improvement of the autoantibody profile. In humans the presumed detrimental role of heightened blood CRP during active RA might be balanced by a beneficial effect of baseline CRP manifest during the pre-clinical stages of disease.