Chronic Humoral Rejection of Human Kidney Allografts Associates With Broad Autoantibody Responses
| Autor: | Julie DeVito, Beow Y. Yeap, Lijuan Xue, Ian Dargon, Timothy C. Girouard, Waichi Wong, Fabrice Porcheray, Emmanuel Zorn, Rosemary Paine, Susan L. Saidman, Robert B. Colvin |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Graft Rejection Male Pathology medicine.medical_specialty Enzyme-Linked Immunosorbent Assay Context (language use) Autoantigens Article Organ transplantation medicine Humans Transplantation Homologous Kidney transplantation Aged Antilymphocyte Serum Autoantibodies Aged 80 and over B-Lymphocytes Transplantation biology Autoantibody Middle Aged medicine.disease Immunohistochemistry Kidney Transplantation Angiotensin II Immunity Humoral Antibody Formation Chronic Disease Immunology biology.protein Drug Therapy Combination Female Antibody Immunosuppressive Agents |
| Zdroj: | Transplantation. 89:1239-1246 |
| ISSN: | 0041-1337 |
| Popis: | Chronic humoral rejection (CHR) is currently recognized as one of the most serious complications after kidney transplantation. The reason why some transplant recipients develop CHR and others do not is still unknown. CHR is primarily characterized by the development of de novo donor-specific antibodies (DSA). These alloantibodies have been directly associated with late graft failure (1–4). In 2005, a series of criteria were adopted to define CHR beyond the development of DSA (5). Because this classification was accepted, a growing number of cases have been diagnosed in different institutions, revealing a higher incidence of CHR than initially presumed. Retrospective studies looking at the deposition of the complement molecule C4d and the development of DSA as markers of antibody-mediated rejection estimated that up to 61% of all chronic rejection cases involved a humoral component (3, 6, 7). In addition, Lee et al. (8) demonstrated that virtually all cases of late graft loss were accompanied by some levels of antibody responses to the allografts. Collectively, these findings suggest that CHR is responsible for a majority of late graft loss cases. In addition to DSA, a number of studies have demonstrated the development of de novo autoantibodies after organ transplantation. Anti-endothelial cell antibodies (AECAs) have been observed for a number of years (9, 10). Their detection in the serum or directly in the graft of kidney transplant recipients has been associated with tissue damage and subsequent graft rejection (11). Although recognized targets of AECAs are often alloantigens, it has been shown that these antibodies can also react to self-proteins (12). Additional studies have reported the development of antibodies to specific self-antigens after transplantation. Autoantigenic targets include angiotensin II type 1 receptor (13), agrin (14), tubulin-α, heat shock protein 60 (15), vimentin (15, 16), cardiac myosin (17), cardiolipin (18), and ribosomal protein L7 (19). The detection of these antibodies was associated with graft rejection episodes or hypertension. Increased serum reactivity to nonprotein structures such as phospholipids and oxidized low-density lipoprotein have also been observed in kidney transplant recipients (20–23). These antibodies were associated with atherosclerosis, a common feature among late transplant recipients and patients with CHR. Overall, these studies demonstrated the presence of various types of autoantibodies in transplant recipients. We hypothesized that such autoantibodies develop more frequently after organ transplantation than initial studies indicated. We also surmised that this humoral autoimmunity could reveal an underlying context of immunologic imbalance that may also have facilitated the generation of DSA. The aim of the present study was to investigate the development and specificity of autoantibody responses in patients with biopsy-proven CHR. |
| Databáze: | OpenAIRE |
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