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.
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.
Authors: Giuseppe Castellano; Rita Melchiorre; Antonia Loverre; Pasquale Ditonno; Vincenzo Montinaro; Michele Rossini; Chiara Divella; Michele Battaglia; Giuseppe Lucarelli; Gennaro Annunziata; Silvano Palazzo; Francesco Paolo Selvaggi; Francesco Staffieri; Antonio Crovace; Mohamed R Daha; Maurice Mannesse; Sandra van Wetering; Francesco Paolo Schena; Giuseppe Grandaliano Journal: Am J Pathol Date: 2010-02-11 Impact factor: 4.307
Authors: Shannon R Reese; Nancy A Wilson; Yabing Huang; Lucille Ptak; Kenna R Degner; Ding Xiang; Robert R Redfield; Weixiong Zhong; Sarah E Panzer Journal: Transplantation Date: 2021-07-01 Impact factor: 5.385
Authors: Zoltán Prohászka; Lea Munthe-Fog; Thor Ueland; Timea Gombos; Arne Yndestad; Zsolt Förhécz; Mikkel-Ole Skjoedt; Zoltan Pozsonyi; Alice Gustavsen; Lívia Jánoskuti; István Karádi; Lars Gullestad; Christen P Dahl; Erik T Askevold; George Füst; Pål Aukrust; Tom E Mollnes; Peter Garred Journal: PLoS One Date: 2013-04-15 Impact factor: 3.240