PMID- 25606785
OWN - NLM
STAT- MEDLINE
DCOM- 20150615
LR  - 20220311
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 99
IP  - 2
DP  - 2015 Feb
TI  - A phase I/II placebo-controlled trial of C1-inhibitor for prevention of 
      antibody-mediated rejection in HLA sensitized patients.
PG  - 299-308
LID - 10.1097/TP.0000000000000592 [doi]
AB  - BACKGROUND: Antibody-mediated rejection (AMR) is a severe form of rejection, 
      mediated primarily by antibody-dependent complement (C) activation. C1 inhibitor 
      (C1-INH, Berinert) inhibits the classical and lectin pathways of C activation. We 
      performed a randomized, placebo-controlled study using C1-INH in highly 
      sensitized renal transplant recipients for prevention of AMR. METHODS: Twenty 
      highly sensitized patients desensitized with IVIG+rituximab+/-plasma exchange were 
      enrolled and randomized 1:1 to receive plasma-derived human C1-INH (20 
      IU/kg/dose) versus placebo intraoperatively, then twice weekly for 7 doses. Renal 
      function, adverse events (AEs)/serious AEs, C3, C4, and C1-INH levels were 
      monitored and C1q+ HLA antibodies were also blindly assessed. RESULTS: One 
      patient in the C1-INH group versus 2 patients in the placebo group developed 
      serious AEs, but none were related to study drug. Delayed graft function 
      developed in 1 C1-INH subject and 4 in the placebo. The C1-INH trough levels 
      increased with C1-INH treatment. C3 and C4 levels also increased significantly in 
      the C1-INH group compared to placebo. No C1-INH patient developed AMR during the 
      study. Two patients developed AMR after the study. Three placebo patients 
      developed AMR, one during the study. C1q+ donor specific antibodies were reduced 
      in 2 C1-INH treated patients tested, while immunoglobulin G DSA levels showed 
      decreased binding for both groups. CONCLUSIONS: The C1-INH appears safe in the 
      posttransplant period. The C1-INH treatment may reduce ischemia-reperfusion 
      injury. The C1-INH also resulted in significant elevations of C1-INH levels, C3, 
      C4, and reduced C1q+ HLA antibodies. Taken together, the combination of antibody 
      reduction and C1-INH may prove useful in prevention of AMR. Further controlled 
      studies are warranted.
FAU - Vo, Ashley A
AU  - Vo AA
AD  - 1 Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA. 
      2 Immunogenetics Laboratory, University of Pittsburgh Medical Center, Pittsburgh, 
      PA. 3 Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, 
      CA. 4 HLA & Immunogenetics Laboratory, Cedars-Sinai Medical Center, Los Angeles, 
      CA. 5 Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA.
FAU - Zeevi, Adriana
AU  - Zeevi A
FAU - Choi, Jua
AU  - Choi J
FAU - Cisneros, Kristen
AU  - Cisneros K
FAU - Toyoda, Mieko
AU  - Toyoda M
FAU - Kahwaji, Joseph
AU  - Kahwaji J
FAU - Peng, Alice
AU  - Peng A
FAU - Villicana, Rafael
AU  - Villicana R
FAU - Puliyanda, Dechu
AU  - Puliyanda D
FAU - Reinsmoen, Nancy
AU  - Reinsmoen N
FAU - Haas, Mark
AU  - Haas M
FAU - Jordan, Stanley C
AU  - Jordan SC
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Biomarkers)
RN  - 0 (Complement C1 Inhibitor Protein)
RN  - 0 (HLA Antigens)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Isoantibodies)
RN  - 80295-33-6 (Complement C1q)
SB  - IM
MH  - Adult
MH  - Biomarkers/blood
MH  - Complement Activation/*drug effects
MH  - Complement C1 Inhibitor Protein/adverse effects/*therapeutic use
MH  - Complement C1q/immunology
MH  - Double-Blind Method
MH  - Female
MH  - Graft Rejection/immunology/*prevention & control
MH  - Graft Survival/*drug effects
MH  - HLA Antigens/*immunology
MH  - *Histocompatibility
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/*therapeutic use
MH  - Isoantibodies/*blood
MH  - Kidney Failure, Chronic/blood/diagnosis/immunology/*surgery
MH  - Kidney Transplantation/*adverse effects
MH  - Los Angeles
MH  - Male
MH  - Middle Aged
MH  - Plasma Exchange
MH  - Time Factors
MH  - Treatment Outcome
EDAT- 2015/01/22 06:00
MHDA- 2015/06/16 06:00
CRDT- 2015/01/22 06:00
PHST- 2015/01/22 06:00 [entrez]
PHST- 2015/01/22 06:00 [pubmed]
PHST- 2015/06/16 06:00 [medline]
AID - 10.1097/TP.0000000000000592 [doi]
PST - ppublish
SO  - Transplantation. 2015 Feb;99(2):299-308. doi: 10.1097/TP.0000000000000592.