Immunohistochemical evidence of activated lectin pathway in kidney allografts with peritubular capillary C4d deposition.
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.
Imai
Naofumi
N
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. imain@med.niigata-u.ac.jp
Nishi
Shinichi
S
Alchi
Bassam
B
Ueno
Mitsuhiro
M
Fukase
Sachiko
S
Arakawa
Masaaki
M
Saito
Kazuhide
K
Takahashi
Kota
K
Gejyo
Fumitake
F
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015935:Complement C4b / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D012189:Retrospective Studies; D014184:Transplantation, Homologous
D015415:Biomarkers; D037601:Mannose-Binding Lectin; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d