Evaluation of Antibodies Directed Against Two GPCRs, Anti-AT1R and Anti-ETAR, on Kidney Transplant Outcome.
Adult
Aged
Antibodies
/ chemistry
Female
Graft Rejection
/ immunology
HLA Antigens
/ immunology
Humans
Immunosuppressive Agents
/ pharmacology
Kidney Failure, Chronic
/ therapy
Kidney Transplantation
/ methods
Male
Middle Aged
Receptor, Angiotensin, Type 1
/ immunology
Receptor, Endothelin A
/ immunology
Tissue Donors
Transplantation, Homologous
Treatment Outcome
Ac AT1R
Ac ETAR
DSAs
Non-HLA antibodies
antibody-mediated rejection
humoral rejection
kidney transplant
medical death certificates.
Journal
Current protein & peptide science
ISSN: 1875-5550
Titre abrégé: Curr Protein Pept Sci
Pays: United Arab Emirates
ID NLM: 100960529
Informations de publication
Date de publication:
2021
2021
Historique:
received:
05
04
2021
revised:
02
05
2021
accepted:
02
05
2021
entrez:
30
12
2021
pubmed:
31
12
2021
medline:
15
3
2022
Statut:
ppublish
Résumé
The role of an alloimmune response against non-self-antigens is established in organ transplantation. HLA incompatibilities are mainly responsible for this recognition between donor and recipient, but they may also be involved in the reactivity against other alloantigens expressed on the allograft resulting from an autoimmune response developed against selfantigens. Our study aimed to determine the presence of non-anti-HLA antibodies (anti-AT1R and anti-ETAR) in sera from patients with end-stage renal disease, who underwent kidney transplantation in pre- and post-transplantation samples to study their influence on the development and evolution of acute humoral rejections and DSAs. Antibodies (Abs) against two G protein-coupled receptors (GPCRs), angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR), have been detected in the sera of transplant recipients, who experience allograft dysfunction, patients with coronary heart disease, marginal hypertension and refractory, vascular lesions, myocardial hypertrophy and chronic inflammatory diseases, such as atherosclerosis or sclerosis. Kidney graft recipients were monitored for anti-ETAR, -AT1R, and -HLA Abs in pre-and post-transplant evolution, and anti-AT1R and/or -ETAR Abs were detected in 24% of recipients (22.4% with anti-AT1R Abs and 9.8% with anti-ETAR Abs). Due to acute humoral rejection, Graft loss was detected in 6.4% of patients with anti-GPCRs non-HLA Abs, and 3.2% had DSA anti-HLA Abs. In this research, we have described how the function of the anti-GPCRs autoAbs and how these Abs that activate GPCRs could influence graft outcome. In conclusion, there is a high association of non-HLA anti-GPCRs Abs levels with reduced kidney function after transplantation, especially in the presence of DSA anti-HLA Abs. Although more studies are needed, anti-AT1R and anti-ETAR antibodies may be helpful biomarkers that allow the risk of graft loss to be assessed.
Sections du résumé
BACKGROUND
The role of an alloimmune response against non-self-antigens is established in organ transplantation. HLA incompatibilities are mainly responsible for this recognition between donor and recipient, but they may also be involved in the reactivity against other alloantigens expressed on the allograft resulting from an autoimmune response developed against selfantigens.
OBJECTIVE
Our study aimed to determine the presence of non-anti-HLA antibodies (anti-AT1R and anti-ETAR) in sera from patients with end-stage renal disease, who underwent kidney transplantation in pre- and post-transplantation samples to study their influence on the development and evolution of acute humoral rejections and DSAs.
METHODS
Antibodies (Abs) against two G protein-coupled receptors (GPCRs), angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR), have been detected in the sera of transplant recipients, who experience allograft dysfunction, patients with coronary heart disease, marginal hypertension and refractory, vascular lesions, myocardial hypertrophy and chronic inflammatory diseases, such as atherosclerosis or sclerosis.
RESULTS
Kidney graft recipients were monitored for anti-ETAR, -AT1R, and -HLA Abs in pre-and post-transplant evolution, and anti-AT1R and/or -ETAR Abs were detected in 24% of recipients (22.4% with anti-AT1R Abs and 9.8% with anti-ETAR Abs). Due to acute humoral rejection, Graft loss was detected in 6.4% of patients with anti-GPCRs non-HLA Abs, and 3.2% had DSA anti-HLA Abs. In this research, we have described how the function of the anti-GPCRs autoAbs and how these Abs that activate GPCRs could influence graft outcome.
CONCLUSION
In conclusion, there is a high association of non-HLA anti-GPCRs Abs levels with reduced kidney function after transplantation, especially in the presence of DSA anti-HLA Abs. Although more studies are needed, anti-AT1R and anti-ETAR antibodies may be helpful biomarkers that allow the risk of graft loss to be assessed.
Identifiants
pubmed: 34967284
pii: CPPS-EPUB-116508
doi: 10.2174/1389203722666210706163149
doi:
Substances chimiques
Antibodies
0
HLA Antigens
0
Immunosuppressive Agents
0
Receptor, Angiotensin, Type 1
0
Receptor, Endothelin A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
745-757Subventions
Organisme : Instituto de Salud Carlos III (ISCIII), the Spanish Ministry of Economy and Competitiveness
ID : PI15/01370, P19/01194
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.