Anti‐phosphatidylserine/prothrombin complex antibodies in patients with cutaneous vasculitis: Possible involvement in the pathogenesis

Abstract

We assessed the IgG and IgM prevalence of anti‐phosphatidylserine/prothrombin complex (aPS/PT) antibodies (Abs) in patients with vasculitis using a novel commercial ELISA kit. To examine whether aPS/PT Abs were involved in the pathogenesis of cutaneous vasculitis, inbred wild‐type rats were intravenously administered with a rat IgM class aPS/PT monoclonal Ab established previously or with rat immunoglobulins as controls. To express PS on the surface of vascular endothelium, these rats were given a subcutaneous injection of cell‐free histones in advance. Serum IgM aPS/PT Ab levels were elevated in patients with systemic vasculitis with skin involvement and cutaneous arteritis compared to those in patients with systemic vasculitis without skin involvement and healthy controls. There was no significant difference in the serum levels of IgG aPS/PT Abs between the patients and healthy controls. Correspondingly, inbred wild‐type rats intravenously administered with the aPS/PT monoclonal IgM Ab after appropriate priming‐subcutaneous histone injection developed cutaneous vasculitis. Some rats given rat IgM instead of the aPS/PT monoclonal Ab also developed cutaneous vasculitis, whereas vasculitis did not occur in rats given IgG or only priming by histones. We suggested that IgM aPS/PT Abs could be involved in the pathogenesis of cutaneous vasculitis based on these findings.

Recent topics related to etiology and clinical manifestations of cutaneous arteritis

“…Furthermore, Kawakami et al reported that the serum anti-PS/PT IgM antibodies levels were higher in the group of cases of systemic vasculitis with skin involvements (three cases of IgA vasculitis, two cases of eosinophilic granulomatosis with polyangiitis, one case of microscopic polyangiitis, and one case of granulomatosis with polyangiitis) and one case of CA than those in the group of cases of systemic vasculitis without skin involvements (two cases of eosinophilic granulomatosis with polyangiitis, two cases of microscopic polyangiitis, one case of granulomatosis with polyangiitis, one case of rheumatoid vasculitis, and one case of PAN), but no significant difference was observed in the serum anti-PS/PT IgG antibody levels ( 36 ). These results suggest that serum anti-PS/PT IgM antibodies might be involved in the pathogenesis of cutaneous vasculitis.…”

The concise review of etiology, pathology, and treatment strategy of polyarteritis nodosa

“…It was also reported that the titer of anti-PS/PT antibodies in PAN cases with skin symptoms manifesting necrotizing vasculitis decreased significantly after treatments [10] , indicating that anti-PS/PT antibodies serve as markers of PAN. Additionally, Kawakami et al reported that serum anti-PS/PT IgM antibodies were higher in systemic vasculitis cases with skin involvements (3 cases of IgA vasculitis, 2 cases of eosinophilic granulomatosis with polyangiitis, 1 case of microscopic polyangiitis, and 1 case of granulomatosis with polyangiitis) and 1 case of cutaneous arteritis than healthy controls and cases of systemic vasculitis without skin involvements (2 cases of eosinophilic granulomatosis with polyangiitis, 2 cases of microscopic polyangiitis, 1 case of granulomatosis with polyangiitis, 1 case of rheumatoid vasculitis, and 1 case of PAN), but there was no significant difference in serum anti-PS/PT IgG antibody titers, suggesting that serum anti-PS/PT IgM antibodies were involved in the pathogenesis of cutaneous vasculitis [11] . Okano et al reported the overexpression of moesin in affected skin vessels and that the titer of serum anti-moesin antibodies in PAN cases with skin involvements due to necrotizing vasculitis is positively correlated with the Birmingham Vasculitis Activity Score and the Vasculitis Damage Index [10] .…”

The relationship between anti‐phosphatidylserine/prothrombin complex IgM antibodies and cutaneous ulcers in patients with cutaneous vasculitis

“…In the several years since our initial studies, a new IgG and IgM QUANTA Lite™ aPS/PT screen enzyme‐linked immunosorbent assay (ELISA) kit (INOVA Diagnostics, San Diego, CA, USA) has been developed and has become widely used 3 . We have also recently reported on the development of cutaneous vasculitis in inbred wild‐type rats following intravenously administered aPS/PT monoclonal IgM Ab after appropriate priming through subcutaneous histone injection 4 …”

“…To examine whether aPS/PT Abs were involved in the pathogenesis of cutaneous vasculitis, inbred wild‐type rats were intravenously administered with a rat IgM class aPS/PT monoclonal Ab established previously 6 or with rat immunoglobulins as controls after subcutaneous histone injection 4 . We observed the development of cutaneous vasculitis in the wild‐type rats who received both the subcutaneous histone injection and IgM aPS/PT Abs systemic injection, based on histopathological analysis.…”