Antibody-Mediated Rejection of Arterialised Venous Allografts Is Inhibited by Immunosuppression in Rats

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.

Immunosuppressive protocols with tacrolimus after cryopreserved aortal allotransplantation in rats

“…The massive donor specific alloantibody response in mice recipients of cold-stored thoracic aortic allografts during the 30 day follow-up period was observed in the work of Heim et al as well [ 30 ], The delayed therapy with everolimus alone (0.05 mg/kg/day, intraperitoneal application, blood concentration of 10 ±1.0 ng/mL) or in combinations with clopidogrel (1 mg/kg/day, intraperitoneal application) reduced the amount of donor-specific antibodies even if therapy was started on day 7 or on day 14. In our previous work we confirmed the suppressive effect of tacrolimus (0.2 mg/kg/day, intramuscular application from day 1 after transplantation, blood concentration of 5.57 ± 0.96 ng/mL) on donor specific antibody production in rats recipients of venous allografts as well [ 44 ].…”

Efficacy and Safety of Elective Conversion From Sotrastaurin (STN) to Tacrolimus (TAC) or Mycophenolate (MPS) in Stable Kidney Transplant Recipients

“…This fact is in agreement with previous findings, which suggest that higher incidence of DSA and antibody-mediated rejection is associated to CNI-free regimens [15][16][17][18][19] and also that STN has no inhibitory effect on human B-lymphocyte function. 27 Despite the fact that experimental models indicate that TAC suppresses DSA formation, 28 there are no data on the effect of TAC on ongoing humoral reactions. TAC is known for its potential as rescue therapy for refractory cellular rejection, 29,30 but its effect on B-cell infiltrates or on DSA MFI has not been fully explored.…”

Composite venous allograft for femoro-pedal bypass grafting in critical limb ischaemia

“…ukazuje, že kryografty se vyznačují nízkou četností primární průchodnosti, na kterou nemá vliv antikoagulace, přičemž i krátkodobá průchodnost může postačit k vyhojení ischemických defektů a zabránit ztrátě končetiny (30% četnost průchodnosti, resp. 80% četnost záchrany končetiny ročně) [13]. Albertini a spol.…”