Heat Shock Protein Autoantibodies

Heat shock proteins (HSPs) are a wide family of molecular chaperones. The first members of HSPs were observed in cellular stress reactions, especially in thermic changes ascribing their generic names. HSPs can be induced not only following temperature shift but also after other stress pressures such as shear force, cellular injury, and heavy metal intoxication, which all upregulate their expression. In fact, any changes of cellular microenvironment leading to a disturbance of protein integrity will trigger an increased expression of HSPs. Many of them, such as HSP70 and HSP60 subfamilies, are expressed in basal condition as actors of synthesis, protection, and transport of proteins. In all these processes, HSPs will conduct, restore, or maintain the proper folding of proteins to preserve or help to acquire their functions. These purposes make most of them ubiquitously expressed in a similar way to housekeeping proteins. Indeed, knockout animals for HSP60 or GRP75 develop trouble during embryogenesis and are barely viable. Most HSP classifications sort them according to their molecular weights, including subfamilies of HSP90, HSP70, HSP60, HSP40, HSP27, and HSP10. Unfortunately, this classification is not physiologically relevant, especially regarding their implication in autoimmune processes. All HSPs do not derive from the same phylogenic origins. Eukaryotic cells derived from a fusion of eukaryote and mitochondria ancestors. During evolution, both pools of genes mixed with each other to be located either in mitochondria or in the nucleus. Nevertheless, the protein structures of HSPs overall preserve the characteristics of their source. Moreover, HSPs gather proteins from both eukaryotic and bacterial origin, which will later determine their structure and their potential immunogenicity. This feature enlightens the capacity of many HSPs to stimulate pathogen recognition receptors (PRR), which are key elements of innate immunity to detect pathogens during infection.