PMID- 36748802
OWN - NLM
STAT- MEDLINE
DCOM- 20230314
LR  - 20240302
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Print)
IS  - 1600-6135 (Linking)
VI  - 23
IP  - 3
DP  - 2023 Mar
TI  - Anti-HLA antibodies in recipients of CD19 versus BCMA-targeted CAR T-cell 
      therapy.
PG  - 416-422
LID - S1600-6135(22)24777-7 [pii]
LID - 10.1016/j.ajt.2022.11.001 [doi]
AB  - Antibodies against foreign human leukocyte antigen (HLA) molecules are barriers 
      to successful organ transplantation. B cell-depleting treatments are used to 
      reduce anti-HLA antibodies but have limited efficacy. We hypothesized that the 
      primary source for anti-HLA antibodies is long-lived plasma cells, which are 
      ineffectively targeted by B cell depletion. To study this, we screened for 
      anti-HLA antibodies in a prospectively enrolled cohort of 49 patients who 
      received chimeric antigen receptor T-cell therapy (CARTx), targeting naive and 
      memory B cells (CD19-targeted, n = 21) or plasma cells (BCMA-targeted, n = 28) 
      for hematologic malignancies. Longitudinal samples were collected before and up 
      to 1 year after CARTx. All individuals were in sustained remission. We identified 
      4 participants with anti-HLA antibodies before CD19-CARTx. Despite B cell 
      depletion, anti-HLA antibodies and calculated panel reactive antibody scores were 
      stable for 1 year after CD19-CARTx. Only 1 BCMA-CARTx recipient had pre-CARTx 
      low-level anti-HLA antibodies, with no follow-up samples available. These data 
      implicate CD19(neg) long-lived plasma cells as an important source for anti-HLA 
      antibodies, a model supported by infrequent HLA sensitization in BCMA-CARTx 
      subjects receiving previous plasma cell-targeted therapies. Thus, plasma 
      cell-targeted therapies may be more effective against HLA antibodies, thereby 
      enabling improved access to organ transplantation and rejection management.
CI  - Copyright (c) 2022 American Society of Transplantation & American Society of 
      Transplant Surgeons. Published by Elsevier Inc. All rights reserved.
FAU - Hill, Joshua A
AU  - Hill JA
AD  - Departments of Medicine, University of Washington School of Medicine, Seattle, 
      Washington, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer 
      Center, Seattle, Washington, USA; Clinical Research Division, Fred Hutchinson 
      Cancer Center, Seattle, Washington, USA. Electronic address: 
      jahill3@fredhutch.org.
FAU - Kiem, Erika S
AU  - Kiem ES
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 
      Washington, USA.
FAU - Bhatti, Atif
AU  - Bhatti A
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 
      Washington, USA.
FAU - Liu, Winnie
AU  - Liu W
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 
      Washington, USA.
FAU - Keane-Candib, Jacob
AU  - Keane-Candib J
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 
      Washington, USA.
FAU - Fitzpatrick, Kristin S
AU  - Fitzpatrick KS
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 
      Washington, USA; Laboratory Medicine and Pathology, University of Washington 
      School of Medicine, Seattle, Washington, USA.
FAU - Boonyaratanakornkit, Jim
AU  - Boonyaratanakornkit J
AD  - Departments of Medicine, University of Washington School of Medicine, Seattle, 
      Washington, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer 
      Center, Seattle, Washington, USA.
FAU - Gardner, Rebecca A
AU  - Gardner RA
AD  - Seattle Children's Research Institute, Seattle, Washington, USA; Pediatrics, 
      University of Washington School of Medicine, Seattle, Washington, USA.
FAU - Green, Damian J
AU  - Green DJ
AD  - Departments of Medicine, University of Washington School of Medicine, Seattle, 
      Washington, USA; Clinical Research Division, Fred Hutchinson Cancer Center, 
      Seattle, Washington, USA.
FAU - Maloney, David G
AU  - Maloney DG
AD  - Departments of Medicine, University of Washington School of Medicine, Seattle, 
      Washington, USA; Clinical Research Division, Fred Hutchinson Cancer Center, 
      Seattle, Washington, USA.
FAU - Turtle, Cameron J
AU  - Turtle CJ
AD  - Departments of Medicine, University of Washington School of Medicine, Seattle, 
      Washington, USA; Clinical Research Division, Fred Hutchinson Cancer Center, 
      Seattle, Washington, USA.
FAU - Smith, Jodi M
AU  - Smith JM
AD  - Seattle Children's Research Institute, Seattle, Washington, USA; Pediatrics, 
      University of Washington School of Medicine, Seattle, Washington, USA.
FAU - Gimferrer, Idoia
AU  - Gimferrer I
AD  - Immunogenetics/HLA laboratory Bloodworks Northwest, Seattle, Washington, USA.
FAU - Blosser, Christopher D
AU  - Blosser CD
AD  - Departments of Medicine, University of Washington School of Medicine, Seattle, 
      Washington, USA; Pediatrics, University of Washington School of Medicine, 
      Seattle, Washington, USA.
FAU - Jackson, Shaun W
AU  - Jackson SW
AD  - Laboratory Medicine and Pathology, University of Washington School of Medicine, 
      Seattle, Washington, USA; Seattle Children's Research Institute, Seattle, 
      Washington, USA; Pediatrics, University of Washington School of Medicine, 
      Seattle, Washington, USA. Electronic address: shaun.jackson@seattlechildrens.org.
LA  - eng
GR  - R01 AR073938/AR/NIAMS NIH HHS/United States
GR  - U01 CA247548/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230112
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (B-Cell Maturation Antigen)
RN  - 0 (Antigens, CD19)
SB  - IM
MH  - Humans
MH  - *Immunotherapy, Adoptive
MH  - B-Cell Maturation Antigen
MH  - Antigens, CD19
MH  - B-Lymphocytes
MH  - *Hematologic Neoplasms
PMC - PMC10266802
MID - NIHMS1902576
OTO - NOTNLM
OT  - B cell biology
OT  - Desensitization
OT  - alloantibody
OT  - clinical research/practice
OT  - immunosuppressant - fusion proteins and monoclonal antibodies: B cell specific
OT  - immunosuppression/immune modulation
OT  - organ transplantation in general
OT  - panel reactive antibody (PRA)
OT  - solid organ transplantation
OT  - translational research/science
EDAT- 2023/02/08 06:00
MHDA- 2023/03/15 06:00
PMCR- 2024/03/01
CRDT- 2023/02/07 06:57
PHST- 2022/06/14 00:00 [received]
PHST- 2022/10/05 00:00 [revised]
PHST- 2022/11/06 00:00 [accepted]
PHST- 2023/02/08 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/02/07 06:57 [entrez]
PHST- 2024/03/01 00:00 [pmc-release]
AID - S1600-6135(22)24777-7 [pii]
AID - 10.1016/j.ajt.2022.11.001 [doi]
PST - ppublish
SO  - Am J Transplant. 2023 Mar;23(3):416-422. doi: 10.1016/j.ajt.2022.11.001. Epub 
      2023 Jan 12.