The most prominent histologic lesion in antibody-mediated rejection is microvascular inflammation (MVI); however, its recognition and scoring can be challenging and poorly reproducible between pathologists. We developed a dual immunohistochemical (IHC)-stain (anti-CD34/anti-CD45 for endothelium/leukocytes) as ancillary tool to improve on the semi-quantitative Banff scores and allow quantification of MVI. We examined the relationship between CD34–CD45 IHC-based quantitative MVI score (the inflamed peritubular capillary ratio, iptcr) and renal-graft failure or donor-specific antibodies (DSA) strength at the time of biopsy. Quantitative iptcr score was significantly associated with renal graft failure (hazard ratio 1.81, per 1 SD-unit [0.13 points] of iptcr-increase; P = 0.026) and predicted the presence and strength of DSA (ordinal odds ratio: 2.42; P = 0.005; 75 biopsies/60 kidney transplant recipients; 30 HLA- and/or ABO-incompatible). Next, we assessed inter-pathologist agreement for ptc score and ptc extent (focal/diffuse) using CD34–CD45 IHC as compared to conventional stain. Compared to conventional stain, CD34–CD45 IHC significantly increased inter-pathologist agreement on ptc score severity and extent (κ-coefficient from 0.52–0.80 and 0.46–0.68, respectively, P < 0.001). Our findings show that CD34–CD45 IHC improves reproducibility of MVI scoring and facilitates MVI quantification and introduction of a dual anti-CD34/CD45 has the potential to improve recognition of MVI ahead of DSA results.

Microvascular inflammation in renal allograft biopsies assessed by endothelial and leukocyte co-immunostain: a retrospective study on reproducibility and clinical/prognostic correlates / Delsante, Marco; Maggiore, Umberto; Levi, Jonathan; Kleiner, David E.; Jackson, Annette M.; Arend, Lois J.; Hewitt, Stephen M.; Carter-Monroe, Naima; Bagnasco, Serena M.; Rosenberg, Avi Z.. - In: TRANSPLANT INTERNATIONAL. - ISSN 0934-0874. - 32:3(2019), pp. 300-312. [10.1111/tri.13371]

Microvascular inflammation in renal allograft biopsies assessed by endothelial and leukocyte co-immunostain: a retrospective study on reproducibility and clinical/prognostic correlates

Delsante, Marco;Maggiore, Umberto;
2019-01-01

Abstract

The most prominent histologic lesion in antibody-mediated rejection is microvascular inflammation (MVI); however, its recognition and scoring can be challenging and poorly reproducible between pathologists. We developed a dual immunohistochemical (IHC)-stain (anti-CD34/anti-CD45 for endothelium/leukocytes) as ancillary tool to improve on the semi-quantitative Banff scores and allow quantification of MVI. We examined the relationship between CD34–CD45 IHC-based quantitative MVI score (the inflamed peritubular capillary ratio, iptcr) and renal-graft failure or donor-specific antibodies (DSA) strength at the time of biopsy. Quantitative iptcr score was significantly associated with renal graft failure (hazard ratio 1.81, per 1 SD-unit [0.13 points] of iptcr-increase; P = 0.026) and predicted the presence and strength of DSA (ordinal odds ratio: 2.42; P = 0.005; 75 biopsies/60 kidney transplant recipients; 30 HLA- and/or ABO-incompatible). Next, we assessed inter-pathologist agreement for ptc score and ptc extent (focal/diffuse) using CD34–CD45 IHC as compared to conventional stain. Compared to conventional stain, CD34–CD45 IHC significantly increased inter-pathologist agreement on ptc score severity and extent (κ-coefficient from 0.52–0.80 and 0.46–0.68, respectively, P < 0.001). Our findings show that CD34–CD45 IHC improves reproducibility of MVI scoring and facilitates MVI quantification and introduction of a dual anti-CD34/CD45 has the potential to improve recognition of MVI ahead of DSA results.
2019
Microvascular inflammation in renal allograft biopsies assessed by endothelial and leukocyte co-immunostain: a retrospective study on reproducibility and clinical/prognostic correlates / Delsante, Marco; Maggiore, Umberto; Levi, Jonathan; Kleiner, David E.; Jackson, Annette M.; Arend, Lois J.; Hewitt, Stephen M.; Carter-Monroe, Naima; Bagnasco, Serena M.; Rosenberg, Avi Z.. - In: TRANSPLANT INTERNATIONAL. - ISSN 0934-0874. - 32:3(2019), pp. 300-312. [10.1111/tri.13371]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2856785
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