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NDT Advance Access published online on April 27, 2006

Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl210
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received July 10, 2005
Accepted March 24, 2006


Original Article

Immunohistochemical evidence of activated lectin pathway in kidney allografts with peritubular capillary C4d deposition

Naofumi Imai 1 *, Shinichi Nishi 2, Bassam Alchi 1, Mitsuhiro Ueno 1, Sachiko Fukase 1, Masaaki Arakawa 1, Kazuhide Saito 3, Kota Takahashi 3, and Fumitake Gejyo 1

1 Division of Clinical Nephrology and Rheumatology, Niigata University Hospital, Niigata, Japan
2 Blood Purification Center, Niigata University Hospital, Niigata, Japan
3 Division of Urology, Niigata University Graduate School of Medical and Dental Sciences, Niigata University Hospital, Niigata, Japan

* To whom correspondence should be addressed.
Naofumi Imai, E-mail: imain{at}med.niigata-u.ac.jp



  Abstract

Background. Complement 4d (C4d) deposition in the peritubular capillary (PTC) in the kidney allograft is a useful diagnostic marker for humoral rejection. C4d is produced not only by the classical pathway but also by the lectin pathway of the complement activation cascade. We have recently reported the in situ role of the later phase of the complement cascade in renal allografts with C4d deposition; however, the initial process prior to C4d deposition is yet to be resolved.

Methods. To clarify the early phases of the complement activation cascade, we evaluated the deposition of initial proteins of the above two pathways; IgG, IgM, mannose-binding lectin (MBL), H-ficolin, L-ficolin, MBL-associated serine protease (MASP)-1 and MASP-2 in kidney allografts with PTC C4d deposition.

Results. Sixty kidney allograft specimens were divided into two groups on the basis of the presence of C4d deposition in PTC. The C4d-positive group (n = 18) included nine ABO-identical and nine ABO-incompatible cases, and the C4d-negative group (n = 42) had 34 ABO-identical and eight ABO-compatible (but not identical) cases. In the C4d-positive group, 16 of 18 cases showed diffuse H-ficolin and IgM deposition in PTC. In contrast, H-ficolin and IgM were not detected in PTC in the C4d-negative group. Other initial proteins were not detected in all cases.

Conclusions. Our study suggested for the first time that the lectin pathway activated by H-ficolin may be involved in C4d deposition on PTC in the kidney allograft.

Keywords: C4d; ficolin; kidney allograft; lectin pathway; peritubular capillary; rejection.
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