Acute antibody-mediated humoral rejection in ABO-compatible and ABO-incompatible renal transplantations: correlation between the histology, C4d deposits in peritubular capillaries and anti-HLA and anti-ABO antibodies.


*Yukiko Kanetsuna, *Yutaka Yamaguchi,** Masahiro Abe,** Shigeru Horita,
**Kazunari Tanabe, **Shohei Fuchinoue, **Hiroshi Toma

 *Department of pathology, Jikei University Kashiwa Hospital, Kashiwa, Chiba, Japan
**Kidney center, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan


Content:

Acute antibody-mediated humoral rejection (AHR) is a major problem in renal allografts that have led to failures soon after transplantation (Tx). C4d deposits in peritubular capillaries (PTC) are one of the most important histological features indicating of AHR. In reviews of the recipient files of living-related ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) renal Txs, 40 cases that showed acute graft failure in early transplant period and were histologically diagnosed as acute humoral and/or vascular rejection were selected. For immunofluorescence for C4d deposition in PTC, the frozen section specimens were stained with anti-C4d (Quidel, USA) in indirect method. Anti-HLA antibody (Ab) was retrospectively observed by flow cytometry using the kit (one lambda) and anti-ABO Ab was detected by indirect Combs' test and saline method.

Results: In 16 patients with ABO-C, anti-HLA Abs were observed in 11 at the first biopsy and in 3 at the last. 6 out of 14 with anti-HLA Abs had graft loss. In 24 patients with ABO-I, only anti-ABO Abs, combined anti-ABO and anti-HLA Abs and only anti-HLA Abs were observed in 9 patients, 8 and 5, respectively. Graft loss was seen in 3, 4 and 2, respectively. In the histological comparison on the first and last biopsies between 14 with anti-HLA Abs in ABO-C and 9 with only anti-ABO Abs in ABO-I, their incidences of endarteritis, glomerulitis, thrombosis and tubulitis at the first biopsy in ABO-C were much more higher than those in ABO-I, and at the last biopsies were also more in ABO-C except for thrombosis. In cases with combined anti-HLA and anti-ABO Abs and only anti-HLA Abs in ABO-I, their incidences of endarteritis and glomerulitis were increased, compared by those in cases with only anti-ABO Abs. In C4d deposition in PTC, strong positivity was seen at the first biopsy both in ABO-C and ABO-I, while at the last biopsy their positivity was fairly decreased in ABO-C, especially for recovered cases.

Conclusion: 

The heterogeneity of acute Ab-mediated humoral rejection was observed in ABO-C and ABO-I. Anti-HLA Ab-mediated humoral rejection may much more develop to the cascade of endarteritis or infiltrative vasculopathy, compared to that with anti-ABO Abs. As mentioned above, I would like to emphasize the histological heterogeneity of anti-donor antibodies in antibody-mediated humoral rejection and less significance of C4d deposition in ABO-incompatible transplantation.

 

 



 

 

Acute antibody-mediated humoral rejection in ABO-compatible and ABO-incompatible renal transplantations: correlation between the histology, C4d deposits in peritubular capillaries and anti-HLA and anti-ABO antibodies.


*Yukiko Kanetsuna, *Yutaka Yamaguchi,** Masahiro Abe,** Shigeru Horita,
**Kazunari Tanabe, **Shohei Fuchinoue, **Hiroshi Toma

 *Department of pathology, Jikei University Kashiwa Hospital, Kashiwa, Chiba, Japan
**Kidney center, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan

 

E-mail address of Yukiko Kanetsuna is as follows:
kanetsuna@mui.biglobe.ne.jp