Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
[bald]Background[/bald] We previously reported that IL-6 inhibition by anti-IL6R antibody (mMR16-1) or CD28 pathway inhibition using CTLA4Ig (abatacept) reduced recall alloantibody responses in a mouse model of allo-sensitization. Here, we interrogated the effectiveness of combining anti-IL6R and abatacept on recall alloantibody responses.
[bald]Methods[/bald] C57BL/6 mice were pre-sensitized with skin allograft (SG) from a HLA.A2 transgenic mice. At Day 90 the pre-sensitized mice were challenged with a second HLA.A2+ SG. The recipients were divided into 8 dosing groups. Group-1 (SS): sterile water at days 0, 2, 7, 14, 21 post-1st skin grafting (P1SG) and at days 0, 2, 7, 14 and 21 post 2nd skin grafting (P2SG). Group-2 (SA): sterile water dosing at days 0, 2, 7, 14, 21 P1SG and abatacept dosing (500ug/dose at days 0, 2, 7, 14, 21 P2SG. Group-3 (AA): abatacept dosing at days 0, 2, 7, 14, 21 P1SG and abatacept during P2SG. Group-4 (AS): abatacept dosing at days 0, 2, 7, 14, 21 P1SG and sterile water dosing P2SG. Group-5 (SS+mMR16-1): dosing as Group-1 plus anti-IL6R dosing (20mg/kg) daily for 14 days P2SG. Group-6 (SA+mMR16-1): dosing as Group-2 plus anti-IL6R dosing P2SG. Group-7 (AS+mMR16-1): abatacept dosing as Group-4 and anti-IL6R dosing P2SG. Group-8 (AA+mMR16-1): abatacept dosing as Group-3 plus anti-IL6R P2SG. Recall alloantibody responses were monitored by measurement of donor-specific antibodies (DSA) in a flow-cytometric antibody binding assay.
[bald]Results[/bald] Levels of DSA IgG (serum anti-HLA.A2) at day 14 P2SG, as measured in mean fluorescent intensity (MFI) were 478.5+-164.1 in Group-1 (SS), 212.7+-167.9 in Group-2 (SA, p=0.0195, v.s Group-1), 125.1+-37.8 in Group-3 (AA, p= 0.02 vs. Group-1), 216.3+-113 in Group-4 (AS, p=0.021), 349.6+-201.3 in Group-5 (SS+mMR16-1, p=0.04) , 271.5+-69.1 in Group-6 (SA+mMR16-1, p=0.05), 203+-126 in Group-7 (AS+mMR16-1, p=0.021) and 81.4+-61.2 in Group-8 (AA+mMR16-1, p=0.023).
[bald]Conclusion[/bald] The combined use of abatacept and mMR16-1 resulted in the most intense suppression of HLA-A2 recall responses. These findings suggest that combining both immune regulatory agents yields superior results and may have clinical implications for desensitization and treatment of antibody mediated rejection in highly-HLA sensitized patients.
To cite this abstract in AMA style:Chai N-N, Wu G, Kim I, Klein A, Jordan S. Combined Anti-IL6R and CTLA4Ig Therapy Attenuates Recall Alloantibody Responses in a Mouse Model of HLA Sensitization [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/combined-anti-il6r-and-ctla4ig-therapy-attenuates-recall-alloantibody-responses-in-a-mouse-model-of-hla-sensitization/. Accessed November 25, 2020.
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