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. 2011 Sep;11(9):1868-76.
doi: 10.1111/j.1600-6143.2011.03593.x. Epub 2011 Jun 14.

High mean fluorescence intensity donor-specific anti-HLA antibodies associated with chronic rejection Postliver transplant

J G O'Leary  1 , H Kaneku, B M Susskind, L W Jennings, M A Neri, G L Davis, G B Klintmalm, P I Terasaki
Affiliations

High mean fluorescence intensity donor-specific anti-HLA antibodies associated with chronic rejection Postliver transplant

J G O'Leary et al. Am J Transplant. 2011 Sep.

Abstract

In contrast to kidney transplantation where donor-specific anti-HLA antibodies (DSA) negatively impact graft survival, correlation of DSA with clinical outcomes in patients after orthotopic liver transplantation (OLT) has not been clearly established. We hypothesized that DSA are present in patients who develop chronic rejection after OLT. Prospectively collected serial serum samples on 39 primary OLT patients with biopsy-proven chronic rejection and 39 comparator patients were blinded and analyzed for DSA using LABScreen(®) single antigen beads test, where a 1000 mean fluorescence value was considered positive. In study patients, the median graft survival was 15 months, 74% received ≥ one retransplant, 20% remain alive and 87% had ≥ one episode of acute rejection. This is in contrast to comparator patients where 69% remain alive, and no patient needed retransplant or experienced rejection. Thirty-six chronic rejection patients (92%) and 24 (61%) comparator patients had DSA (p = 0.003). Chronic rejection versus comparator patients had higher mean fluorescence intensity (MFI) DSA. Although a further study with larger numbers of patients is needed to identify clinically significant thresholds, there is an association of high-MFI DSA with chronic rejection after OLT.

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Conflict of interest statement

Personal Financial Interests:

P.I.T.—One Lambda Incorporated Chairman and major share holder. H.K. was a consultant for One Lambda. All the other authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

Figures

Figure 1
Figure 1
Antibody profile of the (A) chronic rejection group and (B) comparator group. Each patient is represented by a bar and the DSA status is represented by different colors. (Six patients in the chronic rejection group are not depicted because only one sample was available for analysis.) All patients in the comparator group who died, dies >5 years after transplant with a normally functioning graft.
Figure 2
Figure 2
Highest mean fluorescent intensity (MFI) donor-specific antibody (DSA) for (A) preformed class I (mean MFI 4075 vs. 1027), (B) preformed class II (mean MFI 2849 vs. 1209), (C) post-OLT class I (mean MFI 1858 vs. 600) and (D) post-OLT class II (mean MFI 9930 vs. 3637). + represents each patient’s maximum value, line represents the group’s mean value.
Figure 3
Figure 3
Total mean fluorescent intensity (MFI) of donor-specific antibodies (DSA) = the addition of each individual DSA per patient. (A) Preformed total class I (mean MFI 7381 vs. 1942), (B) preformed total class II (mean MFI 3782 vs. 1813), (C) post-OLT total class I (mean MFI 2610 vs. 728) and (D) post-OLT total class II (mean MFI 17 353 vs. 3839). + represents each patient’s maximum value, line represents the group’s mean value.
Figure 4
Figure 4
Graft survival after the first positive DSA in patients with preformed versus de novo DSA (A) when positive is MFI > 1000 and (B) when positive is MFI > 5000.
Figure 5
Figure 5
Graft survival after the first positive DSA in patients with class I, class II, and class I and II DSA (A) when positive is MFI > 1000 and (B) when positive is MFI > 5000.
Figure 6
Figure 6
Graft survival after the first positive DSA in the presence and absence of induction with daclizumab or OKT3 (A) when positive is MFI > 1000 and (B) when positive is MFI > 5000.
See this image and copyright information in PMC

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