Peritubular Capillary Basement Membrane Multilayering in Renal Allograft Biopsies of Patients With De Novo Donor-Specific Antibodies

被引：11
作者：
de Kort, Hanneke [1 ,2 ,3 ]
Willicombe, Michelle [4 ]
Brookes, Paul [5 ]
Moran, Linda B. [6 ]
Santos-Nunez, Eva [5 ]
Galliford, Jack W. [4 ]
Taube, David [4 ]
McLean, Adam G. [4 ]
Moss, Jill [6 ]
Cook, H. Terence [1 ,2 ]
Roufosse, Candice [1 ,2 ]
机构：
[1] Univ London Imperial Coll Sci Technol & Med, Dept Med, Ctr Complement & Inflammat Res, Hammersmith Campus, London, England
[2] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Dept Histopathol, London, England
[3] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Renal Transplant Unit, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
[4] Imperial Coll Kidney & Transplant Ctr, London, England
[5] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Histocompatibil & Immunogenet Lab, London, England
[6] Charing Cross Hosp, Imperial Coll Healthcare NHS Trust, Dept Histopathol, Elect Microscopy Unit, London, England
来源：
TRANSPLANTATION | 2016年 / 100卷 / 04期
关键词：
KIDNEY-TRANSPLANT RECIPIENTS; MEDIATED REJECTION; ELECTRON-MICROSCOPY; PROTOCOL BIOPSIES; GLOMERULOPATHY; DIAGNOSIS; C4D; LESIONS; CLASSIFICATION; INFLAMMATION;
D O I：
10.1097/TP.0000000000000908
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Background. Severe peritubular capillary basement membrane multilayering (PTCBML) is part of the Banff definition of chronic antibody-mediated rejection. We retrospectively investigated whether assessment of the mean number of layers of basement membrane (BM) around peritubular capillaries (PTC) can be used in a cohort of patients with de novo donor-specific antibodies (dnDSA) as an early marker to predict long-term antibody-mediated injury. Methods. This is a retrospective cohort study with 151 electron microscopy samples from 54 patients with dnDSA, assessed at around 1 year after transplantation, for a mean number of BM layers around PTC and in serial biopsies. Graft survival and time to transplant glomerulopathy (TG) development were estimated in survival analyses. Results. We found that a mean PTCBML count greater than 2.5 layers assessed in a sample of 25 PTCs around 1 year after transplantation is indicative of the development of TG in patients with dnDSA (P = 0.001). In addition, in patients with serial biopsies available for electron microscopy analysis, we could distinguish 2 groups: patients with a mean PTCBML count of 2.5 or less on all biopsies, and patients who developed greater than 2.5 layers at any time after transplantation. The latter group reflected dnDSA patients at risk for TG development (P < 0.001). In patients with dnDSA, PTCBML score added significantly to the sensitivity and specificity of prediction of TG compared with microcirculation injury score alone. Conclusions. Our results highlight the potential value of assessing the mean number of BM in PTC for early prediction of progression to chronic antibody-mediated injury.
引用
收藏
页码：889 / 897
页数：9
相关论文
共 32 条
[1]   Beyond C4d: the ultrastructural appearances of endothelium in ABO-incompatible renal allografts [J].
Broecker, Verena ;
Pfaffenbach, Annika ;
Habicht, Antje ;
Chatzikyrkou, Christos ;
Kreipe, Hans H. ;
Haller, Hermann ;
Scheffner, Irina ;
Gwinner, Wilfried ;
Zilian, Eva ;
Immenschuh, Stephan ;
Schwarz, Anke ;
Horn, Peter A. ;
Heinemann, Falko M. ;
Becker, Jan U. .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2013, 28 (12) :3101-3109
[2]   Microcirculation Inflammation Associates With Outcome in Renal Transplant Patients With De Novo Donor-Specific Antibodies [J].
de Kort, H. ;
Willicombe, M. ;
Brookes, P. ;
Dominy, K. M. ;
Santos-Nunez, E. ;
Galliford, J. W. ;
Chan, K. ;
Taube, D. ;
McLean, A. G. ;
Cook, H. T. ;
Roufosse, C. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2013, 13 (02) :485-492
[3]   The role of electron microscopy in renal allograft biopsy evaluation [J].
de Kort, Hanneke ;
Moran, Linda ;
Roufosse, Candice .
CURRENT OPINION IN ORGAN TRANSPLANTATION, 2015, 20 (03) :333-342
[4]   Specificity of intertubular capillary changes: Comparative ultrastructural studies in renal allografts and native kidneys [J].
Drachenberg, CB ;
Steinberger, E ;
HoehnSaric, E ;
Heffes, A ;
Klassen, DK ;
Bartlett, ST ;
Papadimitriou, JC .
ULTRASTRUCTURAL PATHOLOGY, 1997, 21 (03) :227-233
[5]   Identifying Specific Causes of Kidney Allograft Loss [J].
El-Zoghby, Z. M. ;
Stegall, M. D. ;
Lager, D. J. ;
Kremers, W. K. ;
Amer, H. ;
Gloor, J. M. ;
Cosio, F. G. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2009, 9 (03) :527-535
[6]   Transplant glomerulopathy: Subclinical incidence and association with alloantibody [J].
Gloor, J. M. ;
Sethi, S. ;
Stegall, M. D. ;
Park, W. D. ;
Moore, S. B. ;
DeGoey, S. ;
Griffin, M. D. ;
Larson, T. S. ;
Cosio, F. G. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2007, 7 (09) :2124-2132
[7]   Peritubular capillary basement membrane reduplication in allografts and native kidney disease - A clinicopathologic study of 278 consecutive renal specimens [J].
Gough, J ;
Yilmaz, A ;
Miskulin, D ;
Gedeon, I ;
Burama, A ;
Yilmaz, S ;
Supanj, F ;
Muruve, D ;
McKenna, R ;
Benediktsson, H .
TRANSPLANTATION, 2001, 71 (10) :1390-1393
[8]   Banff 2013 Meeting Report: Inclusion of C4d-Negative Antibody-Mediated Rejection and Antibody-Associated Arterial Lesions [J].
Haas, M. ;
Sis, B. ;
Racusen, L. C. ;
Solez, K. ;
Glotz, D. ;
Colvin, R. B. ;
Castro, M. C. R. ;
David, D. S. R. ;
David-Neto, E. ;
Bagnasco, S. M. ;
Cendales, L. C. ;
Cornell, L. D. ;
Demetris, A. J. ;
Drachenberg, C. B. ;
Farver, C. F. ;
Farris, A. B., III ;
Gibson, I. W. ;
Kraus, E. ;
Liapis, H. ;
Loupy, A. ;
Nickeleit, V. ;
Randhawa, P. ;
Rodriguez, E. R. ;
Rush, D. ;
Smith, R. N. ;
Tan, C. D. ;
Wallace, W. D. ;
Mengel, M. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2014, 14 (02) :272-283
[9]   Early Ultrastructural Changes in Renal Allografts: Correlation With Antibody-Mediated Rejection and Transplant Glomerulopathy [J].
Haas, M. ;
Mirocha, J. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2011, 11 (10) :2123-2131
[10]   Potential Impact of Microarray Diagnosis of T Cell-Mediated Rejection in Kidney Transplants: The INTERCOM Study [J].
Halloran, P. F. ;
Pereira, A. B. ;
Chang, J. ;
Matas, A. ;
Picton, M. ;
De Freitas, D. ;
Bromberg, J. ;
Seron, D. ;
Sellares, J. ;
Einecke, G. ;
Reeve, J. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2013, 13 (09) :2352-2363
1234