HSP60 and Anti-HSP60 Antibodies in Vasculitis: They are Two of a Kind

Abstract

Clinical and pathological manifestations present as heterogeneous in vasculitides. Thus, inflammation can affect arteries, arterioles, capillaries, venules, and veins toward major body regions. One common feature of vascular diseases appears to be the presence of anti-HSP60 autoantibodies arising either consecutively to infection and molecular mimicry reaction with bacterial HSP60, or following recognition of endogenous HSP60 translocated or bound onto the surface of stressed endothelial cells. Because their levels are very low in some diseases but strikingly upregulated in others, and because their frequencies vary from one vasculitis to another, anti-HSP60 autoantibodies might play a role in the pathological mechanisms that likely differ among the vascular diseases. Identification of the variety of HSP60 epitope specificities along with each vasculitis would help to understand such discrepancies.

Hsp60 chaperonopathies and chaperonotherapy: targets and agents

“…The actions of Hsp60 could lead to the modification of those proteins, and in this manner it could have a role in many diseases, including carcinogenesis. Heart Heart failure; Coronary vascular disease [137][138][139][140] Kidney Glomerulonephritis [141] Large bowel Inflammatory bowel diseases [19,142,143] Lung Chonic obstructive pulmonary disease [20] Oral cavity Periodontitis [144,145] Pancreas Type 1 diabetes [146][147][148][149][150][151] Skin Scleroderma, pemphigoid; Psoriasis; Dermatomyositis [152,153] Synovial joints Rheumatoid arthritis; Juvenile idiopathic arthritis [154][155][156][157] Vessels Vasculitis; Atherosclerosis [158][159][160][161][162][163][164][165][166][167] Adapted from [2]. Hsp60 seems to contribute to tumor cell survival, but this is controversial.…”

Autoantibodies to Endothelial Cell Surface ATP Synthase, the Endogenous Receptor for Hsp60, Might Play a Pathogenic Role in Vasculatides

“…This indicates that soluble hsp60, whose level is elevated in vasculitides [21], may have protective effects. It remains to determine whether the effectiveness of the protective effect of hsp60 occurs regardless of the specificity of the anti-ATP synthase Ab.…”

“…A minority of resting human umbilical vein EC (HUVEC) bound to soluble hsp60 [15], suggesting that the “danger” signal provided by hsp60 [21] might be detected by an as yet unidentified receptor. To do so, we opted for a Far Western blot (WB) approach.…”

The Ambiguity in Immunology

“…can produce damage via the formation of circulating immune complexes (ICs). The resulting systemic inflammatory processes can provoke damage in various cells (e.g., blood cells) or the formation of vasculitis phenomena, which affect several tissues (e.g., joints, skin, kidney, brain; Oates and Gilkeson, 2002; Rice et al, 2005; Alard et al, 2008; Klareskog et al, 2008). However, these injuries are generally self-limited and rarely cause organ or tissue failure.…”