Kidney Transplantation Under a Tolerogenic Regimen of Recipient Pretreatment and Low-Dose Postoperative Immunosuppression With Subsequent Weaning

Shapiro, Ron; Ml, Jordan; Basu, Amit; Scantlebury,; Potdar, Santosh; Hp, Tan; Ea, Gray; Randhawa, PS; Murase, Noriko; Zeevi, Adriana; Aj, Demetris; Woodward, Jennifer E.; Marcos, Amadeo; Fung, John J.; Starzl, TE

doi:10.1097/01.sla.0000089853.11184.53

Cited by 93 publications

(59 citation statements)

References 12 publications

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“…In clinical transplantation, the possible tolerogenic effect of anti-T-cell antibodies may be inhibited by concomitant long-term immunosuppression. Recently, Starzl et al [25,26] demonstrated an excellent short-term outcome with an extremely low need for systemic immunosuppressants in various organ recipients pre-treated with rabbit polyclonal T cell antibodies. In the intervention study with humanized non-Fc receptor binding anti-CD3 antibodies, Herold et al observed an inverted CD4 + /CD8 + cell ratio 3 months following drug administration [22] which may support the concept of a durable tolerogenic effect.…”

Section: Discussionmentioning

confidence: 99%

Polyclonal Anti-T-Cell Therapy for Type 1 Diabetes Mellitus of Recent Onset

Saudek¹,

Havrdova²,

Bouc̆ek³

et al. 2004

Rev Diab Stud

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■ AbstractThe destruction of pancreatic β-cells in type 1 diabetes mellitus is mediated by autoreactive T-lymphocyte clones. We initiated a prospective randomized controlled trial of polyclonal rabbit anti-T-cell globulin (ATG) in patients with type 1 diabetes within 4 weeks of diagnosis and with residual post-glucagon C-peptide levels still over 0.3 nmol/l. ATG was administered as an initial bolus of 9 mg/kg followed by 3 consecutive doses of 3 mg/kg. An interim analysis was performed to establish whether any significant changes in Cpeptide production and insulin requirement had occurred that would justify the continuation of this pilot study. By May 2004, 11 subjects were assigned to treatment with ATG along with intensified insulin therapy and 6 to intensified insulin therapy with placebo, and were followed for a period of at least 6 months. During the first 12 months a significant difference in the insulin dose trends was found between the groups (p = 0.010) with a lower insulin dosage in the ATG group. There was also a difference in the glucagon stimulated C-peptide level trends of marginal significance (p = 0.068). Compared to values at screening, stimulated Cpeptide levels significantly improved in the ATG group (p = 0.012) but not in the placebo group. Complete diabetes remission occurred in 2 patients in the ATG and in none of the placebo group. Glycosylated hemoglobin at 12 months tended to be lower in the ATG group (p = 0.088). Significant adverse effects of ATG treatment, mainly transient fever and moderate symptoms of serum sickness (7 and 6 subjects, respectively) were observed during the first month only. The interim analysis of this ongoing study suggests that short-term ATG therapy in type 1 diabetes of recent onset contributes to the preservation of residual C-peptide production and to lower insulin requirements in the first year following diagnosis.

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Section: Discussionmentioning

confidence: 99%

Polyclonal Anti-T-Cell Therapy for Type 1 Diabetes Mellitus of Recent Onset

Saudek¹,

Havrdova²,

Bouc̆ek³

et al. 2004

Rev Diab Stud

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“…Despite their early minimization of immunosuppressive therapy, neither patient MM nor CA underwent an acute rejection episode during the 3-y followup period. Shapiro et al's study (14) remains a benchmark trial of minimized tacrolimus monotherapy in renal transplant recipients: In this study, 150 patients were treated with 5 mg/ kg antithymocyte globulin with bolus prednisone as induction and were subsequently treated with tacrolimus monotherapy. Under this regimen, 37% of patients underwent acute rejection by 4 mo.…”

Section: Discussionmentioning

confidence: 99%

Cutting Edge: Immunological Consequences and Trafficking of Human Regulatory Macrophages Administered to Renal Transplant Recipients

Hutchinson

Riquelme

Sawitzki

et al. 2011

The Journal of Immunology

221

236

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Regulatory macrophages (M regs) were administered to two living-donor renal transplant recipients. Both patients were minimized to low-dose tacrolimus monotherapy within 24 wk of transplantation and subsequently maintained excellent graft function. After central venous administration, most M regs remained viable and were seen to traffic from the pulmonary vasculature via the blood to liver, spleen, and bone marrow. By 1 y posttransplantation, both patients displayed patterns of peripheral blood gene expression converging upon the IOT-RISET signature. Furthermore, both patients maintained levels of peripheral blood FOXP3 and TOAG-1 mRNA expression within the range consistent with nonrejection. It is concluded that M regs warrant further study as a potential immune-conditioning therapy for use in solid-organ transplantation. The results of this work are being used to inform the design of The ONE Study, a multinational clinical trial of immunomodulatory cell therapy in renal transplantation.

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“…The baseline CAN scores averaged from 1.3 to 2.0 to 2.6 in the three successively compiled series. The acceptance of kidneys with an increasing incidence and severity of preexisting 18 6 17 40 9 16 donor disease reflected nationwide efforts to expand the organ pool, ie, by relaxing the criteria for organ acceptance.…”

Section: Chronic Allograft Nephropathymentioning

confidence: 99%