The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation
CD86 molecule is the ligand for both costimulatory (CD28) and coinhibitory (CTLA-4) molecules, and it regulates immune response after allogeneic hematopoietic stem cell transplantation (alloHSCT). Therefore, we postulate that CD86 gene variations might influence the outcome after alloHSCT. Altogethe...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2018/3826989 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832553286750699520 |
|---|---|
| author | Lidia Karabon Miroslaw Markiewicz Karolina Chrobot Monika Dzierzak-Mietla Edyta Pawlak-Adamska Anna Partyka Anna Koclega Slawomira Kyrcz-Krzemien Irena Frydecka |
| author_facet | Lidia Karabon Miroslaw Markiewicz Karolina Chrobot Monika Dzierzak-Mietla Edyta Pawlak-Adamska Anna Partyka Anna Koclega Slawomira Kyrcz-Krzemien Irena Frydecka |
| author_sort | Lidia Karabon |
| collection | DOAJ |
| description | CD86 molecule is the ligand for both costimulatory (CD28) and coinhibitory (CTLA-4) molecules, and it regulates immune response after allogeneic hematopoietic stem cell transplantation (alloHSCT). Therefore, we postulate that CD86 gene variations might influence the outcome after alloHSCT. Altogether, 295 adult patients (pts) undergoing related (105 pts) and unrelated (190 pts) donor-matched HSCT were genotyped for the following CD86 gene polymorphisms: rs1129055, rs9831894, and rs2715267. Moreover, the donors’ rs1129055 polymorphism was determined. None of the investigated SNPs alone were associated with aGvHD and rate of relapse. However, we showed that rs2715267 SNP influenced overall survival (OS) after alloHSCT. The 24-month OS for the rs271526GG recipients was worse than that for the recipients possessing T allelle (TT or GT genotypes) (p=0.009). Moreover, analysis of gene-gene interaction between CD86 and CTLA-4 showed that having both the A allele for CD86 rs1129055 and the CTLA-4 CT60GG genotype in recipients increased the risk of aGvHD about 3.5 times. Interestingly, the donors’ rs1129055GG genotype and the recipients’ CT60GG genotype also increased the risk of aGvHD about 2.7-fold. We postulate that recipients’ CD86 gene polymorphisms influence the overall survival after alloHSCT and, together with CTLA-4 polymorphisms, might be considered a risk factor for aGvHD. |
| format | Article |
| id | doaj-art-b4786dbbe5b04b0580d1a72464febf85 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-b4786dbbe5b04b0580d1a72464febf852025-02-03T05:54:29ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/38269893826989The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell TransplantationLidia Karabon0Miroslaw Markiewicz1Karolina Chrobot2Monika Dzierzak-Mietla3Edyta Pawlak-Adamska4Anna Partyka5Anna Koclega6Slawomira Kyrcz-Krzemien7Irena Frydecka8Department of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, R Weigl 12, 53-114 Wroclaw, PolandDepartment of Hematology and Bone Marrow Transplantation, School of Medicine in Katowice, Medical University of Silesia, Dabrowskiego 25, 40-032 Katowice, PolandDepartment of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, R Weigl 12, 53-114 Wroclaw, PolandDepartment of Hematology and Bone Marrow Transplantation, School of Medicine in Katowice, Medical University of Silesia, Dabrowskiego 25, 40-032 Katowice, PolandDepartment of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, R Weigl 12, 53-114 Wroclaw, PolandDepartment of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, R Weigl 12, 53-114 Wroclaw, PolandDepartment of Hematology and Bone Marrow Transplantation, School of Medicine in Katowice, Medical University of Silesia, Dabrowskiego 25, 40-032 Katowice, PolandDepartment of Hematology and Bone Marrow Transplantation, School of Medicine in Katowice, Medical University of Silesia, Dabrowskiego 25, 40-032 Katowice, PolandDepartment of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, R Weigl 12, 53-114 Wroclaw, PolandCD86 molecule is the ligand for both costimulatory (CD28) and coinhibitory (CTLA-4) molecules, and it regulates immune response after allogeneic hematopoietic stem cell transplantation (alloHSCT). Therefore, we postulate that CD86 gene variations might influence the outcome after alloHSCT. Altogether, 295 adult patients (pts) undergoing related (105 pts) and unrelated (190 pts) donor-matched HSCT were genotyped for the following CD86 gene polymorphisms: rs1129055, rs9831894, and rs2715267. Moreover, the donors’ rs1129055 polymorphism was determined. None of the investigated SNPs alone were associated with aGvHD and rate of relapse. However, we showed that rs2715267 SNP influenced overall survival (OS) after alloHSCT. The 24-month OS for the rs271526GG recipients was worse than that for the recipients possessing T allelle (TT or GT genotypes) (p=0.009). Moreover, analysis of gene-gene interaction between CD86 and CTLA-4 showed that having both the A allele for CD86 rs1129055 and the CTLA-4 CT60GG genotype in recipients increased the risk of aGvHD about 3.5 times. Interestingly, the donors’ rs1129055GG genotype and the recipients’ CT60GG genotype also increased the risk of aGvHD about 2.7-fold. We postulate that recipients’ CD86 gene polymorphisms influence the overall survival after alloHSCT and, together with CTLA-4 polymorphisms, might be considered a risk factor for aGvHD.http://dx.doi.org/10.1155/2018/3826989 |
| spellingShingle | Lidia Karabon Miroslaw Markiewicz Karolina Chrobot Monika Dzierzak-Mietla Edyta Pawlak-Adamska Anna Partyka Anna Koclega Slawomira Kyrcz-Krzemien Irena Frydecka The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation Journal of Immunology Research |
| title | The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation |
| title_full | The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation |
| title_fullStr | The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation |
| title_full_unstemmed | The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation |
| title_short | The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation |
| title_sort | influence of genetic variations in the cd86 gene on the outcome after allogeneic hematopoietic stem cell transplantation |
| url | http://dx.doi.org/10.1155/2018/3826989 |
| work_keys_str_mv | AT lidiakarabon theinfluenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT miroslawmarkiewicz theinfluenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT karolinachrobot theinfluenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT monikadzierzakmietla theinfluenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT edytapawlakadamska theinfluenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT annapartyka theinfluenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT annakoclega theinfluenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT slawomirakyrczkrzemien theinfluenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT irenafrydecka theinfluenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT lidiakarabon influenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT miroslawmarkiewicz influenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT karolinachrobot influenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT monikadzierzakmietla influenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT edytapawlakadamska influenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT annapartyka influenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT annakoclega influenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT slawomirakyrczkrzemien influenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation AT irenafrydecka influenceofgeneticvariationsinthecd86geneontheoutcomeafterallogeneichematopoieticstemcelltransplantation |