Background: Rejection is considered as a major barrier to achieve successful transplantation. Non self-human leucocyte antigen (HLA) is a well-known antigenic target for antibodies binding that can result in antibody-mediated rejection (AMR). To reduce risk of rejection in kidney transplant, preventive measures are undertaken, which include HLA-matching between donor and recipient, and in-vitro pre-transplant crossmatch with potential donor cells and recipient sera, furthermore, periodic HLA antibodies monitoring for donor-specific antibodies (DSA) is carried out before and after transplant. Nevertheless, allograft may still fail despite the above measures, which suggests other antigens besides HLA can also contribute to renal rejection. In fact, polymorphic major histocompatibility complex (MHC) class I–related chain A (MICA) antigens and Angiotensin II type 1 receptor (AT1R) antigens have been reported as likely targets in AMR. However, the effect of non-HLA antibodies such as anti-MICA and anti-AT1R antibodies in rejection are not fully defined. This implies there is an imminent need to elucidate the role of non-HLA antibodies in allograft AMR cases which are not mediated by HLA antibodies. Aim: To retrospectively evaluate the occurrence of MICA and AT1R antibodies in 21 clinical AMR cases without detectable HLA antibodies or HLA antibodies that were not target against donor HLA. Methods: Twenty-one cases with suspected non-HLA mediated post-transplant rejection were retrieved. Eplet analysis was utilized to confirm that the detectable HLA-DR antibodies in one of the samples were not cross-reactive towards a donor’s antigen. Sera from 21 non-AMR cases were used as controls. All sera were subjected to MICA antibody and AT1R antibody screening. Identified positive cases were further examined with their pre-transplant sera to assess whether the AT1R and/or MICA antibodies were already pre-formed before transplantation. The sensitization histories of transfusion, pregnancy and previous transplantation were recorded. Results: Nine of twenty-one cases were detected with MICA and/or AT1R antibodies. 7 samples were detected with MICA antibodies while 3 samples were detected with AT1R antibodies. A sample was detected with both MICA and AT1R antibodies. Importantly, the presence of MICA/AT1R antibodies appeared to be strongly associated with rejection caused by non-HLA antigens (p=0.0007). All controlled cases were found to be negative for MICA and AT1R antibodies. Pre-transplant sera of the positive cases were further screened and pre-formed antibodies were detected in 3 of the positive MICA cases, and 1 of the positive AT1R cases. Since no AT1R and MICA genotyping of the donor was carried out previously, it was uncertain that the allograft rejection was induced by the donor specific pre-formed antibodies generated in the pre-transplant sensitization events. Nonetheless, AT1R and MICA antibodies appeared to be induced by the allograft in the remaining 5 cases. Conclusion: Presence of MICA/AT1R antibodies appeared to be associated with the investigated AMR cases without detectable HLA antibodies. Some evidence suggested the production of these non-HLA antibodies could be induced by transfusion sensitization or allograft upon transplantation. / published_or_final_version / Pathology / Master / Master of Medical Sciences

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 5 uppsatser.

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Bibliography: leaves 206-254. / xiii, 254 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Analyses the cytokine gene expression and the manipulation of these responses in order to offer some insights into the Th1 and Th2 responses associated with allograft rejection. Supports the concept that the unmodified alloimmune response involves complex interactions between Th1-like, Th2-like and APC-derived cytokines. Immunomodulation of the alloimmune response is associated with the down regulation of multiple cytokines within both Th1 and Th2 populations with concurrent upregulation of IL-10 expression. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1998?

Bibliography: leaves 206-254. / xiii, 254 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Analyses the cytokine gene expression and the manipulation of these responses in order to offer some insights into the Th1 and Th2 responses associated with allograft rejection. Supports the concept that the unmodified alloimmune response involves complex interactions between Th1-like, Th2-like and APC-derived cytokines. Immunomodulation of the alloimmune response is associated with the down regulation of multiple cytokines within both Th1 and Th2 populations with concurrent upregulation of IL-10 expression. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1998?

Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1998? / Bibliography: leaves 206-254.

The populations of cells which infiltrate tissue allografts in W mutant mice and their non-mutant littermates were investigated using the light and electron microscopes. Initially, thyroid allografts were attempted but this tissue proved unsatisfactory for comparative studies and skin was used instead. The cells infiltrating the skin grafts were isolated enzymatically and characterized using the light microscope. In addition, cells in epon sections of skin grafts were identified using the electron miscroscope. The frequency of the various cell types isolated from grafts in mutant mice differed significantly from that of cells isolated from grafts in non-mutant mice. The electron microscope studies indicated that the cell types infiltrating skin allografts are the same in both mutant and non-mutant hosts. / Science, Faculty of / Zoology, Department of / Graduate

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