Calreticulin’s Role(s) in Autoimmune Disorders

Abstract

For over ten years autoantibodies (Aab) against calreticulin (CRT) have been reported in a number of autoimmune disorders including rheumatoid arthritis, Sjögren’s syndrome, celiac disease and complete congenital heart block. The most studied group is patients with systemic lupus erythematosus (SLE), where Aab against CRT have been detected in 40% of all patients. A number of studies have sought to assess the pathogenicity of such antibodies. The production of CRT Aab shows similarities to classical heat shock stress responses such as hsp90, 70 and 60. Aab to CRT and hsp may penetrate living cells and interfere with cell function. Moreover since CRT plays an immunoregulatory role with antigen presentation through the MHC class I pathway, Aab may interfere with this important process. Furthermore, there is extensive evidence to show CRT binds to the first component of complement— C1q. This leads to a number of consequences; first, C1q binding to CRT prevents Aab against CRT binding to CRT. It has been observed in individuals with low levels of C1q, a higher rate of photosensitive lupus occurs. Second, C1q may bind to CRT on the cell surface of apoptotic neutrophils enhancing their clearance. In lupus patients, C1q does not appear to bind to these cells and therefore apoptotic mechanisms may be impaired in lupus patients. Third, CRT interaction with C1q leads to inhibition of classical complement activation that might control the inflammatory response to immune complex accumulation. This chapter reviews the immune related functions of CRT and the multistage pathogenic considerations of CRT autoantibody production. KeywordsSystemic Lupus ErythematosusCeliac DiseaseSysremic Lupus Erythematosus PatientPrimary Biliary CirrhosisRubella VirusThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.