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COMMENTARY
Year : 2017  |  Volume : 4  |  Issue : 3  |  Page : 73-74

Extent of peritubular capillaritis in renal allograft biopsies: Unfolding the story: A commentary on an article from the transplantation journal


Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan

Date of Web Publication28-Sep-2017

Correspondence Address:
Muhammed Mubarak
Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi
Pakistan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jina.jina_10_17

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How to cite this article:
Mubarak M. Extent of peritubular capillaritis in renal allograft biopsies: Unfolding the story: A commentary on an article from the transplantation journal. J Integr Nephrol Androl 2017;4:73-4

How to cite this URL:
Mubarak M. Extent of peritubular capillaritis in renal allograft biopsies: Unfolding the story: A commentary on an article from the transplantation journal. J Integr Nephrol Androl [serial online] 2017 [cited 2017 Dec 11];4:73-4. Available from: http://www.journal-ina.com/text.asp?2017/4/3/73/215735



Peritubular capillaries (PTCs), along with glomerular capillaries, represent one of the major targets of antibody-mediated rejection (AMR). In these compartments, the allo-inflammatory response is characterized by the presence of inflammatory cells in the lumen of these structures, as opposed to the traditional inflammatory lesions of other body structures, where the inflammatory cell infiltration in the wall, stroma, or parenchyma of the organ is necessary for the diagnosis of the inflammatory condition. The inflammation of PTCs is designated as peritubular capillaritis (ptc) and is one of the components of microcirculation inflammation (MI), as shown in [Figure 1]. The later has emerged as one of the important diagnostic features of c4d-negative AMR.[1],[2],[3] However, ptc is not 100% specific for AMR and may be seen in cases of T-cell-mediated rejection and acute tubular necrosis. Hence, the need for determining the extent (focal vs. diffuse) of ptc and the scoring (ptc 0–3) of these lesions.[2],[3] Patterns of ptc in renal allograft biopsies vary considerably from case to case depending on the extent, score (intensity of ptc), and cellular composition. These patterns may correlate with chronic allograft injury and graft loss and thus may be of predictive value. One of the main parameters of ptc, which a pathologist must report during the study of allograft biopsy, is the extent of the process. In a recent study, Kozakowski et al.[4] evaluated the diagnostic and prognostic value of ptc characteristics in a cross-sectional study of 85 patients, in which the data on donor-specific antibodies (DSAs) were also available. The patients were recruited based on the results of cross-sectional AMR screening of 741 patients in the context of an ongoing randomized controlled trial. Inclusion criteria included age >18 years, with functioning allograft (estimated glomerular filtration rate >20 mL/min/1.7 m 2) for ≥180 days. Among these, 111 (15%) patients were found to be DSA-positive and thus eligible for study-related protocol biopsy; 25 of these were not considered for study-related protocol biopsies because of exclusion criteria or other reasons. One patient was excluded because of inadequate biopsy tissue for detailed morphological study. The biopsies were obtained after a mean of 7.4 ± 6.3 years after transplantation, i.e., these were late rejections. The authors reevaluated the biopsies for the extent (focal vs. diffuse), score, and cellular composition in relation to DSA binding strength (mean fluorescence intensity [MFI]). The ptc parameters were also correlated with chronic allograft injury lesions (chronic transplant glomerulopathy [TG] or chronic lesion score [CLS]). Ptc was found in 50% of cases with 76% mononuclear cells. Diffuse ptc was found in 64% and focal in 36%. Diffuse ptc correlated significantly with higher MFI of DSAs (median: 4407 vs. 2419 for focal ptc [P = 0.04]), higher CLS scores (mean: 6.81 vs. 4.67 for focal ptc [P = 0.01], and TG (58% vs. no ptc, 24% [P = 0.02]. Moreover, diffuse ptc was the only parameter of PTC which was independently related to CLS. The association of ptc score ≥2 with TG was slightly better than for diffuse ptc. Diffuse ptc and ptc score of ≥2 remained independently related to TG after adjusting for c4d, DSA MFI, or previous rejection episodes but lost their independent association when adjusted for total MI scores. The authors concluded that the extent of ptc is clinically relevant and should be reported, in addition to ptc score and the composition of the cellular infiltrate.
Figure 1: Morphological and immunopathological features of antibody-mediated rejection. (a) Medium-power view showing many peritubular capillaries with many inflammatory cells in the lumina, consistent with peritubular capillaritis (ptc) (H and E, ×200). (b) Medium-power view showing one large peritubular capillary with ptc score of 3 (H and E, ×200). (c) High-power view of a glomerulus showing many capillary lumina partially obliterated by infiltrating inflammatory cells, consistent with glomerulitis (H and E, ×400). (d) c4d immunofluorescence showing bright, linear positivity of c4d along peritubular capillaries (IF for c4d, ×200)

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Conventionally, four components of the renal graft parenchyma were thought to be important for the diagnosis and classification of rejection. These were involved by the rejection process either singly or in variable combinations. These components included glomeruli, blood vessels (mainly arteries), tubules, and the interstitium. PTCs were not separately assessed or scored in earlier Banff schemas. With the widespread recognition of AMR and the use of additional tools for diagnosis of humoral component, it soon became apparent that PTCs are an important target of the alloantibodies and these assumed a central role in the diagnosis of AMR. Thus, ptc is one of the important diagnostic criterion for the diagnosis of c4d-negative AMR. PTCs are also more amply samples as compared to glomeruli and may prove useful in marginal or inadequate biopsy samples. More recent updates of Banff classification have given due importance to this lesion as a diagnostic tool of AMR and have formulated criteria for characterizing ptc in more detail.[5],[6],[7],[8],[9],[10] This lesion is also being explored as a possible prognostic tool for long-term graft outcome, and the study by Kozakowski et al. is one such effort.[4] There is a need for more prospective studies incorporating extent, score, and composition of ptc, in addition to other scoring options to fine tune the diagnostic and prognostic value of this important lesion. A Banff working group on ptc is the need of the hour for multicenter studies of ptc to optimize interobserver agreement and clinical validity of the lesion and to fine tune the morphology of ptc.



 
  References Top

1.
Haas M. Pathology of C4d-negative antibody-mediated rejection in renal allografts. Curr Opin Organ Transplant 2013;18:319-26.  Back to cited text no. 1
    
2.
Haas M. C4d-negative antibody-mediated rejection in renal allografts: Evidence for its existence and effect on graft survival. Clin Nephrol 2011;75:271-8.  Back to cited text no. 2
    
3.
Haas M. Emerging concepts and controversies in renal pathology: C4d-negative and arterial lesions as manifestations of antibody-mediated transplant rejection. Surg Pathol Clin 2014;7:457-67.  Back to cited text no. 3
    
4.
Kozakowski N, Eskandary F, Herkner H, Bond G, Oberbauer R, Regele H, et al. Diffuse extent of peritubular capillaritis in late antibody-mediated rejection: Associations with levels of donor-specific antibodies and chronic allograft injury. Transplantation 2017;101:e178-87.  Back to cited text no. 4
    
5.
Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff '07 classification of renal allograft pathology: Updates and future directions. Am J Transplant 2008;8:753-60.  Back to cited text no. 5
    
6.
Sis B, Mengel M, Haas M, Colvin RB, Halloran PF, Racusen LC, et al. Banff '09 meeting report: Antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant 2010;10:464-71.  Back to cited text no. 6
    
7.
Mengel M, Sis B, Haas M, Colvin RB, Halloran PF, Racusen LC, et al. Banff 2011 meeting report: New concepts in antibody-mediated rejection. Am J Transplant 2012;12:563-70.  Back to cited text no. 7
    
8.
Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, et al. Banff 2013 meeting report: Inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 2014;14:272-83.  Back to cited text no. 8
    
9.
Loupy A, Haas M, Solez K, Racusen L, Glotz D, Seron D, et al. The Banff 2015 kidney meeting report: Current challenges in rejection classification and prospects for adopting molecular pathology. Am J Transplant 2017;17:28-41.  Back to cited text no. 9
    
10.
Mubarak M, Kazi JI. Evolution of the diagnostic criteria of antibody-mediated rejection of renal allografts: Banff classification updates. Port J Nephrol Hypertens 2013;27:137-42.  Back to cited text no. 10
    


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