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Clinical Outcome of Patients With De Novo C1q Binding Donor-Specific HLA Antibodies After Renal Transplantation

J. Bamoulid,1 A. Roodenburg,2 O. Staeck,1 C. Schoenemann,2 N. Lachmann,2 K. Budde.1

1Nephrology, Charite Hospital-University of Medicine, Berlin, Germany
2HLA Laboratory, Charite Hospital-University of Medicine, Berlin, Germany.

Meeting: 2015 American Transplant Congress

Abstract number: A291

Keywords: HLA antibodies, Kidney transplantation, Rejection

Session Information

Session Name: Poster Session A: Late Breaking

Session Type: Poster Session

Date: Saturday, May 2, 2015

Session Time: 5:30pm-7:30pm

 Presentation Time: 5:30pm-7:30pm

Location: Exhibit Hall E

A. Not all de novo donor-specific HLA antibodies (dnDSA) are causing immediate graft loss. The importance of complement-binding DSA was recently shown with a commercial C1q Luminex assay. We developed a modified C1q-Luminex assay (Lachmann N et al, Transplantation 2013;95:694-700.) showing a higher sensitivity as compared to the CDC assay and hypothesize that, with this assay, we could differentiate between harmful (ABMR) or harmless dnDSA (stable clinical course).

B. We selected 59 renal transplant recipients (RTR) with dnDSA, available serum samples and sufficient follow-up after 1st dnDSA detection. Samples were both tested with screening Luminex and single antigen assays for dnDSA and with our modified assay for the presence of C1q-binding IgG dnDSA (C1q+).

C. 37 (63%) developed ABMR (mean follow-up 37±28 mths). 22 (37%) had no clinical/biological signs of graft dysfunction (mean follow-up 34±17 mths). Groups were comparable for baseline and donor characteristics. ABMR RTR had a significant higher frequency of class I (59% vs. 23%) or class I+II dnDSA (51% vs. 9%) and more pregnancies (88% vs. 17%) (p<0.01). Significantly more ABMR RTR had C1q+. The mean C1q+ MFI was significantly higher in the ABMR group (table1).

C1q dnDSA positivity according to the occurence of a biopsy-proven ABMR during follow-up.
  dnDSA+ ABMR (n=37) dnDSA+ no ABMR (N=22) P*
C1q+ dnDSA classe I and/or II n. (%) 27(73) 9(41) 0.014
Mean MFI C1q+ dnDSA positivity (±SD) 5482±4498 2291±3348 0.005
* X2 test for percentage; T test for mean The median survival (1.04 vs. 4.74 yrs) and proportion of RTR without ABMR after dnDSA detection were significantly lower in C1q+ RTR (figure1). The sensitivity and specificity of the test were 73% and 59% with a PPV and NPV of 75% and 57%, respectively.

D. We demonstrate the clinical relevance of C1q-binding dnDSA on clinical allograft outcome. Not all RTR C1q+ have a poor outcome, specificity was only moderate. Yet, the assay was shown to be a useful tool to stratify the immunological risk for ABMR after detection of dnDSA.

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To cite this abstract in AMA style:

Bamoulid J, Roodenburg A, Staeck O, Schoenemann C, Lachmann N, Budde K. Clinical Outcome of Patients With De Novo C1q Binding Donor-Specific HLA Antibodies After Renal Transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/clinical-outcome-of-patients-with-de-novo-c1q-binding-donor-specific-hla-antibodies-after-renal-transplantation/. Accessed May 17, 2025.

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