Ripoll, VM;
Lambrianides, A;
Pierangeli, SS;
Poulton, K;
Ioannou, Y;
Heywood, WE;
Mills, K;
... Giles, IP; + view all
(2014)
Changes in regulation of human monocyte proteins in response to IgG from patients with antiphospholipid syndrome.
Blood
, 124
(25)
pp. 3808-3816.
10.1182/blood-2014-05-577569.
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Abstract
The effects of IgG from patients with the antiphospholipid syndrome (APS) upon monocyte activation have not been fully characterised. We carried out a comprehensive proteomic analysis of human monocytes treated with IgG from patients with different manifestations of the APS. Using differential gel electrophoresis (2D DiGE) four of the most significantly regulated proteins: - vimentin (VIM); zinc finger CCH domain containing protein 18; CAP Gly domain containing linker protein 2; and myeloperoxidase - were differentially regulated in monocytes treated with thrombotic or obstetric APS-IgG, compared with healthy control (HC)-IgG. These findings were confirmed by comparing monocytes isolated from APS patients and HC. Anti-VIM antibodies (AVA) were significantly increased in 11 of 27 (40.7%) patients with APS. VIM expression on HC monocytes was stimulated more strongly by APS-IgG from patients with higher avidity serum AVA. We further characterised the proteome of thrombotic APS-IgG treated-monocytes using a label-free proteomics technique. Of 12 proteins identified with the most confidence, two overlapped with 2D DiGE and many possessed immune response, cytoskeletal, coagulation and signal transduction functions which are all relevant to APS and may therefore provide potential new therapeutic targets of this disease.
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