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Absorber Newsletter, May 2010
During the ATC meeting in San Diego, the congress held a workshop focusing on Endothelial Cell Crossmatch on Sunday, May 1. The workshop was chaired by Dr. Kathryn Tinckam, University Health Network, Toronto and Dr. Elaine Reed, David Geffen School of Medicine, UCLA Immunogenetics Center, Los Angeles.
Dr. Tinckam started the workshop with an overview of the current understanding of where we are with anti-endothelial cell antibodies (AECA) in 2010 and pointed out a rationale for why antibodies against the endothelium are important. The endothelium has a critical location between the vascular and the interstitial compartments. It regulates the hemodynamics, angiogenetic vascular remodelling, metabolic, synthetic, anti-inflammatory and anti-thrombotic processes. Dr. Tinckam further described that AECA are common in HLA sensitized renal transplant patients. In a multicenter study by Breimer et al., published in Transplantation 2009, it was found that patients who were positive for non-donor specific HLA antibodies were also positive for AECA in the XM-ONE® assay and had significantly worse kidney function compared to patients who were negative for either HLA or non-HLA antibodies.
Dr. Yael Korin of UCLA described their standard operating procedure of the assay. In their extensive validation program they have, among other findings, shown that retrieving the whole blood in ACD tubes and transfering it to CPT tubes (provided in the XM-ONE® kit) gave results comparable to drawing blood directly into the CPT tubes. This finding is important since donor blood is not normally drawn in the HLA lab. Using the protocol they were able to store healthy volunteer blood for up to 48 hours without affecting cell viability or the crossmatch result. Furthermore, they compared the results using frozen or fresh PBMCs without seeing any difference. Finally, they validated simultaneous crossmatch of T-, B- and endothelial cells. Their findings confirmed that it is possible to do T- and B-cell XM within XM-ONE® with high correlation to standard Lymphocyte XM.
AECA in renal allograft rejection. 18% of the patients showed donor specific anti endothelial cell antibodies
Dr. Anette Jackson from Johns Hopkins University Hospital presented data from her experience with the XM-ONE®. In patients being HLA and ABO compatible they found 18% of their patients (11 of 60) being XM-ONE® positive. This was in a cohort of patients with low (or no) panel reactive antibodies (PRA). There was no significant difference in acute rejections (27% vs 20%) but kidney function differed significantly 3 months post transplantion. In long term follow- up most of the XM-ONE® positive patients were lost (reasons not shown) and the difference in kidney function was equal between the groups. Futhermore, Dr. Jackson presented three case studies from their ABO incompatible kidney transplant program in which patients being XM-ONE® positive in their pretransplant sera had rejections. In one of the cases an XM-ONE® positive patient had post transplant complications with increased S-creatinine, ptc3 and C4d deposition in biopsy. These complications were resolved by double plasmapheresis and upon re-testing with XM-ONE® the patient was negative.
Dr. Elaine Reed led the discussion that followed. One of the questions that was discussed was the clinical significance of autoantibodies and the implications of autotesting. However, current knowledge is not conclusive and further studies are warranted. It was recognized that XM-ONE® positivity highly correlates with the clinical outcome and that the findings in the multicenter study are encouraging when moving forward to a wider clinical use of the test.
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