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Ten Year Follow-Up of Islet Recipients on Anti-LFA1 Therapy: Over-Immunosuppression Leads to Operational Tolerance?

J. Gardner,1 A. Posselt,1 S. Wisel,1 U. Mashirani,2 G. Szot,1 V. Nguyen,1 K. Johnson,1 J. McElroy,1 Q. Tang,1 P. Stock.1

1Surgery, University of California, San Francisco, San Francisco, CA
2Endocrinology, University of California, San Francisco, San Francisco, CA.

Meeting: 2018 American Transplant Congress

Abstract number: 485

Keywords: Immunosuppression, Islets, LFA-1 antigen, Tolerance

Session Information

Date: Tuesday, June 5, 2018

Session Name: Concurrent Session: Pancreas and Islet - 2

Session Time: 2:30pm-4:00pm

 Presentation Time: 3:30pm-3:42pm

Location: Room 4C-3

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Introduction: Ten-year outcomes from a cohort of five pre-uremic islet transplant (txp) recipients treated with anti-leukocyte functional antigen-1 (LFA-1) antibody Efalizumab (EFA) revealed two patients that remain insulin independent with either minimal or complete withdrawal of immunosuppression (IS), prompting investigation of underlying immunologic mechanisms.

Methods: Patients remained on EFA following islet infusion until drug discontinuation on May 1, 2009 (avg treatment 570 days), with transition to CNI-sparing IS. Blood samples were monitored pre- and post-txp for CD4+, CD8+, and regulatory T (Treg) cells. Recipient alloreactivity was evaluated by mixed lymphocyte reactions (MLR) in vitro against donor-specific and third-party stimulated B cells (sBc) for proliferation and cytokine production.

Results/Discussion: Insulin independence at 10 years post-txp was 40% (2/5 patients; Fig 1). Two patients, EFA-2 and EFA-4, remain insulin-independent on minimal to no IS, while a third patient, EFA-1, maintained insulin independence for 3287 days. All five pts showed significant enrichment of peripheral Tregs; notably EFA-4, who remains insulin independent off all IS for 5.4 years, had the highest peak levels of Treg-predominance, reaching 67% of all CD4+ T cells in circulation. Further investigation by proliferation and interferon gamma production after MLR revealed that EFA-2 and EFA-4 had an extended period of non-reactivity to donor and third-party antigen on EFA. Although EFA-4 regained in vitro reactivity to both donor and third party antigen after discontinuation of EFA, the patient remains operationally tolerant and insulin independent off all IS.

Conclusions: In ten-year follow up of islet txp recipients on EFA-based IS, one patient achieved operational tolerance off all IS, with another maintaining insulin independence on minimal IS. Selective enrichment of Tregs and sustained early donor non-reactivity while on EFA correlate with these outcomes.

CITATION INFORMATION: Gardner J., Posselt A., Wisel S., Mashirani U., Szot G., Nguyen V., Johnson K., McElroy J., Tang Q., Stock P. Ten Year Follow-Up of Islet Recipients on Anti-LFA1 Therapy: Over-Immunosuppression Leads to Operational Tolerance? Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Gardner J, Posselt A, Wisel S, Mashirani U, Szot G, Nguyen V, Johnson K, McElroy J, Tang Q, Stock P. Ten Year Follow-Up of Islet Recipients on Anti-LFA1 Therapy: Over-Immunosuppression Leads to Operational Tolerance? [abstract]. https://atcmeetingabstracts.com/abstract/ten-year-follow-up-of-islet-recipients-on-anti-lfa1-therapy-over-immunosuppression-leads-to-operational-tolerance/. Accessed March 3, 2021.

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