ORCID Profile
0000-0002-7239-3814
Current Organisations
Royal Adelaide Hospital
,
SA Pathology
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 30-12-2023
Publisher: Wiley
Date: 09-06-2015
DOI: 10.1111/NEP.12441
Abstract: Acute antibody-mediated rejection can occur in absence of circulating donor-specific antibodies. Agonistic antibodies targeting the anti-angiotensin II type 1 receptor (anti-AT1 R) are emerging as important non-human leucocyte antigen (HLA) antibodies. Elevated levels of anti-angiotensin II receptor antibodies were first observed in kidney transplant recipients with malignant hypertension and allograft rejection. They have now been studied in three separate kidney transplant populations and associate to frequency of rejection, severity of rejection and graft failure. We report 11 cases of biopsy-proven, Complement 4 fragment d (C4d)-negative, acute rejection occurring without circulating donor-specific anti-HLA antibodies. In eight cases, anti-angiotensin receptor antibodies were retrospectively examined. The remaining three subjects were identified from our centre's newly instituted routine anti-angiotensin receptor antibody screening. All subjects fulfilled Banff 2013 criteria for antibody-mediated rejection and all responded to anti-rejection therapy, which included plasma exchange and angiotensin receptor blocker therapy. These cases support the routine assessment of anti-AT1 R antibodies in kidney transplant recipients to identify subjects at risk. Further studies will need to determine optimal assessment protocol and the effectiveness of pre-emptive treatment with angiotensin receptor blockers.
Publisher: Cold Spring Harbor Laboratory
Date: 04-04-2022
DOI: 10.1101/2022.03.28.22272975
Abstract: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare thromboembolic complication of adenoviral-vectored SARS-CoV2 vaccines, mediated by antibodies directed against platelet factor 4 (PF4). Given their causal role in VITT, identification of the molecular composition of anti-PF4 antibodies is crucial for developing better diagnostics and treatments. Here, we utilised a novel proteomic workflow to analyse the immunoglobulin variable (IgV) region composition of anti-PF4 antibodies at the level of the secreted proteome. Serum anti-PF4 IgG antibodies from five patients with VITT triggered by ChAdOx1 nCoV-19 vaccination were affinity purified by PF4-coupled magnetic beads and sequenced by mass spectrometry. We revealed a single IgG heavy (H)-chain species paired with a single lambda light (L)-chain species in all five unrelated patients. Remarkably, all L-chains were encoded by the identical IGLV3-21*02 gene subfamily with identical L-chain third complementarity determining region (LCDR3) lengths. Moreover, striking stereotypic features were also identified in heavy-chains anti-PF4 antibodies characterised by identical HCDR3 length and homologous sequences. In summary, we unravelled the molecular signature of highly stereotyped clonotypic anti-PF4 antibodies, indicating shared pathways of antibody production in VITT patients. These discoveries are critical to understand the molecular basis of this serious condition and develop novel therapies aimed at removing pathogenic clones. Anti-PF4 antibodies in VITT comprise highly stereotyped clonotype A single IGLV3-21*02 encoded light chain is found in unrelated patients
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.PATHOL.2022.07.010
Abstract: Lens-epithelial derived growth factor (LEDGF/DFS70) autoantibodies result in the commonly observed dense fine speckled (DFS) pattern by anti-nuclear antibody (ANA) assay. However, there is no consensus approach for confirmation of this autoantibody specificity. To evaluate current approaches, we examined inter-assay agreement between six anti-LEDGF/DFS70 assays. A total of 395 consecutive sera s les from routine ANA diagnostics were obtained, tested by routine ANA, anti-ENA line immunoblot assay (LIA) and anti-dsDNA assay and with six anti-DFS/LEDGF assays: the EuroLine-LIA (Euro-LIA), Medical and Biological Laboratories ELISA (MBL-ELISA), Phadia-EliA (EliA), QUANTA Flash CLIA, EuroImmun ELISA (Euro-ELISA) and Immco-Diagnostics HEp-2 ELITE/DFS-Knockout (HEp-2KO). Of 395 sera, 108 tested positive by at least one assay. Despite general good concordance between all assays across the cohort (Gwet's AC1=0.89), within the target DFS-ANA pattern group inter-assay agreement was poor (AC1=0.59). Euro-LIA, CLIA and MBL-ELISA assays were most concordant, but CLIA and Euro-LIA were also most likely to identify discordant positive results. EliA and Euro-ELISA had poorer agreement, which could be attributable to ill-matched cut-offs between assays. HEp-2KO was frequently discordant with all other assays tested. Euro-LIA, CLIA and MBL-ELISA were most concordant at manufacturer's specifications and are suited for use in clinical laboratories. Modified assay thresholds are required to ensure comparative results for Euro-ELISA and EliA. HEp-2KO assay is frequently discordant with all other assays, making it less suited for routine diagnostics. The study highlights the importance of considering inter-assay variability when developing a diagnostic strategy for anti-LEDGF/DFS70 autoantibodies in clinical laboratories.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2016
Publisher: Elsevier BV
Date: 12-2021
Publisher: American Society of Hematology
Date: 13-10-2022
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1038/KI.2015.237
No related grants have been discovered for Alexander Troelnikov.