Polyclonal Antilymphocyte Globulin (ATG) & Intestinal Immune Barrier After Kidney Transplantation

Polyclonal Antilymphocyte Globulin (ATG) & Intestinal Immune Barrier After Kidney Transplantation

The prevention of allograft rejection in kidney transplantation requires administering to the patient an immunosuppressive regimen of induction. The induction strategy is based on an injection of polyclonal anti-lymphocyte globulin (ATG-FLAG or fresenius®) driving a lymphocyte lysis, or an injection of monoclonal antibodies directed against non-lymphopenic the α chain of the IL-receptor 2 (anti-CD25 antibody, basiliximab), by immunological risk patients. Our group showed a significant increase in death rates in transplant patients with lymphopenia CD4 continued beyond 2 years of transplantation. This excess mortality is related to complications following chronic inflammation observed in some patients lymphopenic.

Preliminary studies have shown that the induced lymphodéplétion ATG appears to be accompanied by an increase of the bacterial products in the blood of transplanted since a significant increase in the sCD14 is observed in these patients one year. We also observed increased concentrations of LPS in patients in the ATG group. This could indicate a secondary bacterial intestinal translocation to a weakening of intestinal immunity linked to the ATG.

The main objective of the study is to assess the impact of anti-lymphocyte globulin polyclonal on intestinal permeability, estimated by the rate lipopolysaccharide (LPS, a constituent of the cell wall of Gram-negative bacteria) blood after kidney transplantation.

The secondary objectives are to evaluate bacterial translocation, the effect of bacterial translocation on structural and metabolic functions of the intestinal epithelium, chronic inflammation, immune reconstitution, regeneration, activation and proliferation of T lymphocytes, the polymorphism of the LPS receptor that causes the activation of innate immunity and the composition of the intestinal microbiota.

The study population consists of renal transplant patients of Nephrology of the University Hospital of Besancon. Patients will be divided into 2 groups according to induction immunosuppressive therapy prescribed the day of renal transplantation as part of their usual care, ie treatment with anti-lymphocyte globulin polyclonal (ATG-Fresenius®) or antibody treatment monoclonal anti-CD25 (basiliximab Simulect). The patient group treated with anti-CD25 antibody will serve as a control group (no depletion of the immune system) to the group of patients treated with ATG.

Inclusion Criteria:

• Men and women aged 18 to 80 years included
• Postmenopausal women for at least 24 months, sterilized surgically, or for women of childbearing age, use an effective method of contraception (oral contraceptives, contraceptive injections, intrauterine devices, method of double-barrier contraceptive patches)
• Participation in the study ORLY East
• Signature of informed consent for participation indicating that the subject has understood the purpose and procedures required by the study and agrees to participate in the study and comply with the requirements and limitations inherent in this study
• Join a French social security or receiving such a plan

Exclusion Criteria:

• Legal incapacity or limited legal capacity
• Topic unlikely to cooperate in the study and / or low early cooperation by the investigator
• Without health insurance Topic
• Pregnant woman
• Inability to understand the reasons for the study; psychiatric disorders judged by the investigator to be incompatible with the inclusion in the study
• Infectious episode with need for hospitalization older than 1 month
• Active infection by the virus of hepatitis B and / or C
• Active infection by HIV or not
• Patients with inflammatory bowel disease (IBD)
• Patients who have undergone total colectomy