Abstract
Objectives and DesignWe determined in a rat model (1) the presence and dynamics of alloantibodies recognizing MHC complexes on quiescent Brown-Norway (BN) splenic cells in the sera of Lewis (LEW) recipients of Brown-Norway iliolumbar vein grafts under tacrolimus immunosuppression; and (2) the presence of immunoglobulins in the wall of acute rejected vein allografts.Materials and MethodsFlow cytometry was used for the analysis of day 0, 14 and 30 sera obtained from Lewis recipients of isogeneic iliolumbar vein grafts (group A) or Brown-Norway grafts (group B, C) for the presence of donor specific anti-MHC class I and II antibodies. Tacrolimus 0.2 mg/kg daily was administered from day 1 to day 30 (group C). Histology was performed on day 30.ResultsSera obtained preoperatively and on day 30 were compared in all groups. The statistically significant decrease of anti MHC class I and II antibody binding was observed only in allogenic non-immunosuppressed group B (splenocytes: MHC class I - day 0 (93%±7% ) vs day 30 (66%±7%), p = 0.02, MHC class II - day 0 (105%±3% ) vs day 30 (83%±5%), p = 0.003; B-cells: MHC class I - day 0 (83%±5%) vs day 30 (55%±6%), p = 0.003, MHC class II - day 0 (101%±1%) vs day 30 (79%±6%), p = 0.006; T-cells: MHC class I - day 0 (71%±7%) vs day 30 (49%±5%), p = 0.04). No free clusters of immunoglobulin G deposition were detected in any experimental group.ConclusionArterialized venous allografts induce strong donor-specific anti-MHC class I and anti-MHC class II antibody production with subsequent immune-mediated destruction of these allografts with no evidence of immunoglobulin G deposition. Low-dose tacrolimus suppress the donor-specific antibody production.
Highlights
There remain a group of vascular patients with critical leg ischemia who are not suitable for the use of greater saphenous vein or prosthetic grafts in peripheral vascular reconstruction
The statistically significant decrease of anti major histocompatibility complex (MHC) class I and II antibody binding was observed only in allogenic non-immunosuppressed group B (splenocytes: MHC class I - day 0 (93%67% ) vs day 30 (66%67%), p = 0.02, MHC class II - day 0 (105%63% ) vs day 30 (83%65%), p = 0.003; Bcells: MHC class I - day 0 (83%65%) vs day 30 (55%66%), p = 0.003, MHC class II - day 0 (101%61%) vs day 30 (79%66%), p = 0.006; T-cells: MHC class I - day 0 (71%67%) vs day 30 (49%65%), p = 0.04)
The results of the transplantation, histology, immunohistochemistry, and cell-mediated rejection of iliolumbar vein grafts were presented in detail previously.[12]
Summary
There remain a group of vascular patients with critical leg ischemia who are not suitable for the use of greater saphenous vein or prosthetic grafts in peripheral vascular reconstruction. Allogeneic veins are used in these patients.[1] allogeneic veins are immunogenic because of the expression of both class I and class II major histocompatibility complex (MHC) antigens on their wall cells.[2] These antigens stimulate immune responses in the host that lead to the destruction of the allovenous wall structure. One possibility for increasing the patency rates of venous allografts is the use of immunosuppressive drugs.[5] immunosuppression is not routinely used in clinical practice.[1] When immunosuppression is used, cyclosporine A is the most frequently administered drug to patients with allovenous bypasses.[6,7,8]
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