| 1. |
- Alheim, M., et al.
(författare)
-
The outcome of the endothelial precursor cell crossmatch test in lymphocyte crossmatch positive and negative patients evaluated for living donor kidney transplantation
- 2013
-
Ingår i: Human Immunology. - : Elsevier BV. - 0198-8859 .- 1879-1166. ; 74:11, s. 1437-1444
-
Tidskriftsartikel (refereegranskat)abstract
- The presence of human leukocyte antigen (HLA) and non-HLA antibodies (Abs) in kidney transplant recipients is associated with graft rejections. This study reports the results of an endothelial precursor cell crossmatch (EPCXM) test for detection of non-HLA Abs and its correlation to lymphocyte crossmatch (LXM) test results, the degree and type of sensitization, and transplantation (Tx) outcome in patients evaluated for living donor (LD) kidney transplantation (Krx). Patients were tested before any pre-transplantation (pre-Tx) treatment and at Tx. Pre-Tx treatments included B cell depletion and Ab removal. Patient records were reviewed for assessment of renal graft function, results of biopsies, and identification of complications affecting the graft. Pre-Tx sera from 32% of the LD patients had IgG and/or IgM-binding donor EPCs. Twenty-five percent of the patients were EPCXM IgM+. Of the patients with negative LXM tests, 25% had EPC Abs mainly of IgM class not reactive with HLA. There was no difference in rejection frequency or serum creatinine levels between the EPCXM+ and EPCXM- groups. The pre-Tx EPCXM+ group had significantly more patients with delayed graft function. Prospective studies with appropriate control groups are needed to establish whether pre-treatments aiming at removing anti-endothelial cell antibodies, as detected by the EPCXM pre-Tx, have a beneficial effect on short-term and long-term graft survival. (C) 2013 American Society for Histocompatibility and Immunogenetics.
|
|
| 2. |
- AlMahri, Ayeda, et al.
(författare)
-
Detection of complement-fixing and non-fixing antibodies specific for endothelial precursor cells and lymphocytes using flow cytometry.
- 2012
-
Ingår i: Tissue antigens. - : Wiley. - 1399-0039 .- 0001-2815. ; 80:5, s. 404-15
-
Tidskriftsartikel (refereegranskat)abstract
- Donor human leukocyte antigen (HLA)-specific antibodies (Abs) with the ability to activate complement are associated with an increased risk of early Ab-mediated rejection (AMR) of kidney allografts. In recent years, also non-HLA Abs-binding endothelial cells have been shown to elicit early AMR. Donor-specific anti-endothelial cell Abs escape detection in the pre-transplant evaluation if only lymphocytes are used as target cells in crossmatch tests. We addressed whether endothelial precursor cells (EPCs) could be used for detection of complement-fixing as well as non-fixing Abs and if complement factor and immunoglobulin G (IgG) deposition on co-purified T and B cells correlated to the outcome of the T- and B-cell complement-dependent cytotoxicity assay. Deposition of complement factors C3c and C3d, but not C1q nor C4d, were detected on EPCs and lymphocytes upon incubation with HLA Ab-positive sera. There was a correlation between the amount of C3c deposition and IgG binding on EPCs (R(2) = 0.71, P = 0.0012) and T cells (R(2) = 0.74, P = 0.0006) but not for B cells (R(2) = 0.34, P = 0.059). The specificity and sensitivity for C3d deposition on endothelial precursor cell crossmatch (EPCXM) T cells vs the T complement-dependent cytotoxicity (CDC) assay were 69% and 72%, respectively. The EPCXM B-cell C3d assay had considerably lower sensitivity (39%) than the B CDC assay. Altogether, this novel assay based on the detection of complements factors on EPCs and lymphocytes by flow cytometry may widen the diagnostic repertoire and thereby improve the clinical management of patients undergoing kidney transplantation.
|
|
| 3. |
- Ayeda, Almahri
(författare)
-
The clinical importance of non-HLA specific antibodies in kidney transplantation
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The clinical significance of human leukocyte antigen (HLA) antibodies (Abs) for hyperacute, acute and chronic antibody-mediated rejection (AMR) of kidney allografts has been clearly demonstrated. AMR occurs in the absence of donor-reactive HLA Abs. It is not known how common the problem of AMR by non-HLA Abs is because of lack of suitable assays for their detection. It is believed that the non-HLA Ab population, although heterogenic, is likely to target antigens on donor organ endothelial cells (ECs). We have been involved in the clinical introduction of a flow cytometric (FC) crossmatch (XM) test that permits the detection of Abs reactive with endothelial precursor cells (EPC) isolated from donor peripheral blood. In this context the EPCs may function as surrogates for mature vascular ECs. The work in this thesis describes the adaptation of the EPCXM to detection of complement-fixing HLA and non-HLA Abs using complement fragment-specific antibodies and flow cytometry, describes the outcome of the EPCXM in relation to the conventional lymphocyte XM (LXM), degree of HLA sensitization and transplantation outcome in patients evaluated for living donor (LD) kidney transplantation (Tx), and assesses the long-term renal graft function in patients with a positive EPCXM pre-transplant. In the first paper, we investigated whether EPCs could be used for detection of complement-fixing Abs and if complement factor and IgG deposition on co-purified T and B cells correlated to the outcome of the T- and B-cell complement-dependent cytotoxicity (CDC) XM. Incubation of EPCs with HLA Ab-positive serum samples resulted in deposition of complement factors C3c and C3d, but not C1q nor C4d, on EPCs and co-purified lymphocytes. The amount of C3c deposition and IgG binding on EPCs and T cells, but not B cells, correlated. The specificity and sensitivity for C3d deposition on co-purified T cells vs the T CDC assay were 69% and 72%, while for B cells the sensitivity was considerably lower. In the second paper, we show that 32% of the LD patients had IgG and/or IgMbinding donor EPCs in their pre-Tx sera. Twenty-five percent of the patients were EPCXM IgM+. Of the patients with negative LXM tests, 25% had EPC Abs mainly of IgM class not reactive with HLA. There was no difference in rejection frequency or serum creatinine levels between the EPCXM positive and negative groups, which is in contrast to earlier published results. However, the clinical protocols used in the second paper included Ab pre-Tx treatments such as B cell depletion and Ab removal. The pre-Tx EPCXM positive group had significantly more patients with delayed graft function. In the manuscript we show that the difference in serum creatinine and glomerular filtration rates observed between EPCXM positive and negative groups at three and six months post-Tx disappears hereafter and during the four-year follow-up. The detection of complement factors on EPCs and lymphocytes by flow cytometry allowing detection of complement-fixing non-HLA and HLA Abs widens the diagnostic repertoire that can be offered patients undergoing kidney transplantation and should thereby improve their clinical management. Prospective studies with appropriate control groups are needed to establish whether pre-treatments aiming at removing anti-EC Abs, as detected by the EPCXM pre-Tx, have a beneficial effect on shortand long-term graft survival.
|
|
| 4. |
- Gäbel, Markus, et al.
(författare)
-
A positive pre-transplant endothelial precursor cell crossmatch does not imply reduced long-term kindney graft function
- 2015
-
Ingår i: SOJ Immunology. - : Symbiosis Group. - 2372-0948. ; 3:3, s. 1-6
-
Tidskriftsartikel (refereegranskat)abstract
- A flow cytometric crossmatch test detecting antibodies specific for donor Endothelial Precursor Cells (EPC) was evaluated in a multicenter study in 2005-06. A Positive Pre-Transplant EPC Crossmatch (EPCXM) was associated with a higher frequency of early rejections and reduced renal function at three and six months. The long-term follow-up of all patients (n = 53/147) recruited at our center is reported. Patients were retrospectively evaluated regarding rejections, patient/ graft survival and renal function over a four-year follow-up. As for the whole multicenter study patient population, significantly more early rejections occurred in EPCXM positive compared to EPCXM negative patients (5/7 vs. 5/46, p = 0.002). The EPCXM positive group had higher SCr at three (183 vs. 118 μmol/l, p = 0.01) and six (172 vs. 124 μmol/l, p = 0.02) months compared to the EPCXM negative group, and measured Glomerular Filtration Rate (mGFR) was decreased in the EPCXM positive group at 6 months (50 vs. 29 ml/min, p = 0.01). SCr decreased and mGFR increased over time in the EPCXM negative group, while SCr increased slightly and mGFR decreased slightly in the EPCXM positive group eliminating the difference in renal function between the groups. A positive EPCXM pre-transplantation is associated with higher frequency of early graft rejections, but does not influence long (4 year) term renal function.
|
|
