Autoantibodies to Vimentin Cause Accelerated Rejection of Cardiac Allografts

Mahesh, Balakrishnan; Leong, Hon S.; McCormack, Ann; Sarathchandra, Padmini; Holder, Angela; Rose, Marlene L.

doi:10.2353/ajpath.2007.060728

Cited by 111 publications

(77 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23 Furthermore, AVAs have been identified in other autoimmune rheumatic diseases, including SLE 24 and associated with thrombotic manifestations in accelerated graft versus host disease post solid organ transplantation. 25 In this paper, we have extended the findings of Ortona et al showing that VIM may be important in the pathogenesis of APS. In particular, we have shown: presence of AVA (not anti-VIM/CL) in serum of 40.7% of patients with APS; VIM is upregulated at both the protein and mRNA level in healthy monocytes exposed to APS-IgG; VIM mRNA expression is increased in monocytes extracted from patients with APS in the presence and absence of LPS as an inflammatory stimulus; and that high avidity AVA IgG correlates with increased stimulation of monocyte VIM expression.…”

Section: Discussionsupporting

confidence: 53%

See 1 more Smart Citation

Changes in regulation of human monocyte proteins in response to IgG from patients with antiphospholipid syndrome

Ripoll

Lambrianides

Pierangeli

et al. 2014

Blood

View full text Add to dashboard Cite

Key Points• Comprehensive proteomics analysis in human monocytes exposed to APS-IgG has identified and characterized several novel proteins.• These proteins have functional relevance to the APS.The effects of immunoglobulin G (IgG) from patients with the antiphospholipid syndrome (APS) upon monocyte activation have not been fully characterized. We carried out a comprehensive proteomic analysis of human monocytes treated with IgG from patients with different manifestations of the APS. Using 2-dimensional differential gel electrophoresis (2D DiGE), 4 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 (AVAs) were significantly increased in 11 of 27 patients (40.7%) with APS. VIM expression on HC monocytes was stimulated more strongly by APS IgG from patients with higher-avidity serum AVA. We further characterized the proteome of thrombotic APS IgG-treated monocytes using a label-free proteomics technique. Of 12 proteins identified with the most confidence, 2 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. (Blood. 2014;124(25):3808-3816)

show abstract

Section: Discussionsupporting

confidence: 53%

“…VT and PM IgG also induced similar sets of proteins in both U937 cells and ex vivo monocytes, respectively. Of the 52 proteins induced by VT in U937s, 24 were BLOOD, 11 DECEMBER 2014 x VOLUME 124, NUMBER 25 PROTEOMIC ANALYSIS aPL TREATED HUMAN MONOCYTES 3809…”

Section: Clinical and Laboratory Characteristics Of Individualsmentioning

confidence: 99%

Changes in regulation of human monocyte proteins in response to IgG from patients with antiphospholipid syndrome

Ripoll

Lambrianides

Pierangeli

et al. 2014

Blood

View full text Add to dashboard Cite

show abstract

“…The association between autoantibody and endothelial complement deposition in our experiments suggests, however, that target autoantigens are translocated to the surface of allograft endothelial cells, presumably as a stress response 38,39 to transplantation. This requirement for additional stress may explain why autoimmune responses that develop after heart transplantation do not cause vasculopathy in the recipient's native heart (our own data and previous studies 10,40 ). Similarly, the presence of autoantibody in recipients of heart allografts did not result in overt autoimmune disease, such as glomerulonephritis, perhaps because, in the absence of alloimmune-mediated inflammation, it takes longer (generally Ͼ10 weeks 31 ) than the time-scale of our experiments for autoantibody to effect damage of native organs.…”

Section: Discussionmentioning

confidence: 99%

Donor CD4 T Cells Contribute to Cardiac Allograft Vasculopathy by Providing Help for Autoantibody Production

Win

Rehakova

Negus

et al. 2009

Circ: Heart Failure

View full text Add to dashboard Cite

Background-The development of autoantibody after heart transplantation is increasingly associated with poor graftoutcome, but what triggers its development and whether it has a direct causative role in graft rejection is not clear. Here, we study the development of antinuclear autoantibody in an established mouse model of heart allograft vasculopathy. Methods and Results-Humoral vascular changes, including endothelial complement staining, were present in bm12 heart grafts, explanted 50 days after transplantation. Alloantibody was not detectable, but long-lasting autoantibody responses developed in C57BL/6 recipients from the third week after transplantation. No autoantibody was generated if donor CD4 T cells were depleted before heart graft retrieval or in recipients that lacked B-cell major histocompatibility complex class II expression, indicating that humoral autoimmunity is a consequence of donor CD4 T-cell allorecognition of the major histocompatibility complex class II complex on recipient autoreactive B cells. An effector role for autoantibody in graft rejection was confirmed by abrogation of humoral vascular rejection, and attenuation of vasculopathy, in B-cell deficient recipients and by development of vascular obliteration and accelerated rejection in recipients primed for autoantibody before transplantation. Conclusions-Passenger CD4 T cells within heart transplants can contribute to allograft vasculopathy by providing help to recipient B cells for autoantibody generation. (Circ Heart Fail. 2009;2:361-369.)

show abstract

“…Alloantibodies that develop against the donor organ can recognize several types of antigens (for review, see Dragun 2008): HLA antigens class I and II (Terasaki and Ozawa 2004;Terasaki and Cai 2005), MICA and MICB antigens (MHC class I-related molecules A and B) (Zou et al 2007;Li et al 2010), minor histocompatibility antigens and non-HLA antigens including the angiotensin II type 1 receptor (Dragun et al 2005), vimentin (Mahesh et al 2007), myosin, the ABO blood group antigens (Montgomery et al 2012), perlecan, type IV and VI collagen, agrin, unknown endothelial antigens (Jackson et al 2011b), and ICAM-1 (Lawson et al 2005).…”

Section: Antibodiesmentioning

confidence: 99%