PMID- 35572510
OWN - NLM
STAT- MEDLINE
DCOM- 20220517
LR  - 20220716
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Extracellular Vesicles Mediate Immune Responses to Tissue-Associated 
      Self-Antigens: Role in Solid Organ Transplantations.
PG  - 861583
LID - 10.3389/fimmu.2022.861583 [doi]
LID - 861583
AB  - Transplantation is a treatment option for patients diagnosed with end-stage organ 
      diseases; however, long-term graft survival is affected by rejection of the 
      transplanted organ by immune and nonimmune responses. Several studies have 
      demonstrated that both acute and chronic rejection can occur after 
      transplantation of kidney, heart, and lungs. A strong correlation has been 
      reported between de novo synthesis of donor-specific antibodies (HLA-DSAs) and 
      development of both acute and chronic rejection; however, some transplant 
      recipients with chronic rejection do not have detectable HLA-DSAs. Studies of 
      sera from such patients demonstrate that immune responses to tissue-associated 
      antigens (TaAgs) may also play an important role in the development of chronic 
      rejection, either alone or in combination with HLA-DSAs. The synergistic effect 
      between HLA-DSAs and antibodies to TaAgs is being established, but the underlying 
      mechanism is yet to be defined. We hypothesize that HLA-DSAs damage the 
      transplanted donor organ resulting in stress and leading to the release of 
      extracellular vesicles, which contribute to chronic rejection. These vesicles 
      express both donor human leukocyte antigen (HLA) and non-HLA TaAgs, which can 
      activate antigen-presenting cells and lead to immune responses and development of 
      antibodies to both donor HLA and non-HLA tissue-associated Ags. Extracellular 
      vesicles (EVs) are released by cells under many circumstances due to both 
      physiological and pathological conditions. Primarily employing clinical specimens 
      obtained from human lung transplant recipients undergoing acute or chronic 
      rejection, our group has demonstrated that circulating extracellular vesicles 
      display both mismatched donor HLA molecules and lung-associated Ags (collagen-V 
      and K-alpha 1 tubulin). This review focuses on recent studies demonstrating an 
      important role of antibodies to tissue-associated Ags in the rejection of 
      transplanted organs, particularly chronic rejection. We will also discuss the 
      important role of extracellular vesicles released from transplanted organs in 
      cross-talk between alloimmunity and autoimmunity to tissue-associated Ags after 
      solid organ transplantation.
CI  - Copyright (c) 2022 Ravichandran, Bansal, Rahman, Sureshbabu, Sankpal, Fleming, 
      Bharat and Mohanakumar.
FAU - Ravichandran, Ranjithkumar
AU  - Ravichandran R
AD  - Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, 
      United States.
FAU - Bansal, Sandhya
AU  - Bansal S
AD  - Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, 
      United States.
FAU - Rahman, Mohammad
AU  - Rahman M
AD  - Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, 
      United States.
FAU - Sureshbabu, Angara
AU  - Sureshbabu A
AD  - Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, 
      United States.
FAU - Sankpal, Narendra
AU  - Sankpal N
AD  - Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, 
      United States.
FAU - Fleming, Timothy
AU  - Fleming T
AD  - Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, 
      United States.
FAU - Bharat, Ankit
AU  - Bharat A
AD  - Department of Surgery-Thoracic, Northwestern University, Chicago, IL, United 
      States.
FAU - Mohanakumar, Thalachallour
AU  - Mohanakumar T
AD  - Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, 
      United States.
LA  - eng
GR  - R21 AI123034/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20220427
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antibodies)
RN  - 0 (Autoantigens)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Antibodies
MH  - Autoantigens
MH  - Autoimmunity
MH  - *Extracellular Vesicles
MH  - Graft Rejection
MH  - HLA Antigens
MH  - Histocompatibility Antigens Class I
MH  - Humans
MH  - *Organ Transplantation
PMC - PMC9094427
OTO - NOTNLM
OT  - antibodies
OT  - extracellular vesicles
OT  - immune responses
OT  - tissue-associated self-antigens
OT  - transplantation
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/05/17 06:00
MHDA- 2022/05/18 06:00
PMCR- 2022/01/01
CRDT- 2022/05/16 04:14
PHST- 2022/01/24 00:00 [received]
PHST- 2022/03/28 00:00 [accepted]
PHST- 2022/05/16 04:14 [entrez]
PHST- 2022/05/17 06:00 [pubmed]
PHST- 2022/05/18 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.861583 [doi]
PST - epublish
SO  - Front Immunol. 2022 Apr 27;13:861583. doi: 10.3389/fimmu.2022.861583. eCollection 
      2022.