MIF functional polymorphisms are associated with acute GVHD progression and steroid-refractoriness
IntroductionApproximately 50% of allogeneic hematopoietic stem cell transplantation (HSCT) Q6 recipients develop graft versus host disease (GVHD). Glucocorticoids (GC) are the first line of treatment for both acute and chronic GVHD. Failure to respond to GC [steroid-refractory (SR)] encompasses a ve...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1504976/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849313391552757760 |
|---|---|
| author | Aviran Aharon Batia Avni Daniel Louzoun Shlomo Elias Polina Stepensky Ron Ram Tsila Zuckerman Tsila Zuckerman Roberto Meza-Romero Roberto Meza-Romero Arthur A. Vandenbark Arthur A. Vandenbark Arthur A. Vandenbark Sigal Grisariu Gil Benedek Gil Benedek |
| author_facet | Aviran Aharon Batia Avni Daniel Louzoun Shlomo Elias Polina Stepensky Ron Ram Tsila Zuckerman Tsila Zuckerman Roberto Meza-Romero Roberto Meza-Romero Arthur A. Vandenbark Arthur A. Vandenbark Arthur A. Vandenbark Sigal Grisariu Gil Benedek Gil Benedek |
| author_sort | Aviran Aharon |
| collection | DOAJ |
| description | IntroductionApproximately 50% of allogeneic hematopoietic stem cell transplantation (HSCT) Q6 recipients develop graft versus host disease (GVHD). Glucocorticoids (GC) are the first line of treatment for both acute and chronic GVHD. Failure to respond to GC [steroid-refractory (SR)] encompasses a very poor outcome with high mortality. Macrophage migration inhibitory factor (MIF) is released during transplantation and triggers enhanced and prolonged immune reactions. Persistently elevated levels of MIF have been shown to override both endogenous and exogenous antiinflammatory effects of GC.MethodsTwo functional polymorphisms in the MIF gene, a −794 CATT5–8 microsatellite repeat and a −173 G/C single-nucleotide polymorphism, were analyzed in 86 patients who underwent allogeneic HSCT. We also measured MIF serum levels at different time points before and after HSCT.ResultsFrequencies of MIF high-expression -794 CATT7 containing genotypes were increased in patients with grade III-IV acute GVHD (aGVHD) (36.8%) compared with patients that did not develop aGVHD (5.8%) and patients with grade II aGVHD (0%), (p=0.0019, 0.0080 respectively). We also demonstrated that the frequencies of the MIF-794 CATT7 and -173 C containing genotypes, were significantly associated with steroid-refractory aGVHD (46.6%, 60% respectively) compared to steroid-responsive aGVHD (0%, 5.3% respectively), (p=0.0011, P=0.0007 respectively). We further showed that MIF circulating levels preceded onset of severe aGVHD.DiscussionOur findings suggest that genetically controlled high expression MIF genotypes are associated with aGVHD worsening and could serve as a biomarker enhancing identification and treatment of steroid-refractory disease. |
| format | Article |
| id | doaj-art-e851ad72d299403ea89a40ebe0b244d4 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-e851ad72d299403ea89a40ebe0b244d42025-08-20T03:52:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15049761504976MIF functional polymorphisms are associated with acute GVHD progression and steroid-refractorinessAviran Aharon0Batia Avni1Daniel Louzoun2Shlomo Elias3Polina Stepensky4Ron Ram5Tsila Zuckerman6Tsila Zuckerman7Roberto Meza-Romero8Roberto Meza-Romero9Arthur A. Vandenbark10Arthur A. Vandenbark11Arthur A. Vandenbark12Sigal Grisariu13Gil Benedek14Gil Benedek15Hebrew University-Hadassah Faculty of Medicine, Jerusalem, IsraelDepartment of Bone Marrow Transplantation and Cancer Immunotherapy, Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, IsraelHebrew University-Hadassah Faculty of Medicine, Jerusalem, IsraelDepartment of Bone Marrow Transplantation and Cancer Immunotherapy, Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Bone Marrow Transplantation and Cancer Immunotherapy, Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, IsraelBone Marrow Transplantation and Cellular Therapy Unit, Tel Aviv Medical Center and Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, IsraelThe Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, IsraelDepartment of Neurology, Oregon Health & Science University, Portland, OR, United StatesNeuroimmunology Research, VA Portland Health Care System, Portland, OR, United StatesDepartment of Neurology, Oregon Health & Science University, Portland, OR, United StatesNeuroimmunology Research, VA Portland Health Care System, Portland, OR, United StatesDepartment of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, United StatesDepartment of Bone Marrow Transplantation and Cancer Immunotherapy, Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, IsraelHebrew University-Hadassah Faculty of Medicine, Jerusalem, IsraelTissue Typing and Immunogenetics Unit, Department of Genetics, Hadassah-Hebrew University Medical Center, Jerusalem, IsraelIntroductionApproximately 50% of allogeneic hematopoietic stem cell transplantation (HSCT) Q6 recipients develop graft versus host disease (GVHD). Glucocorticoids (GC) are the first line of treatment for both acute and chronic GVHD. Failure to respond to GC [steroid-refractory (SR)] encompasses a very poor outcome with high mortality. Macrophage migration inhibitory factor (MIF) is released during transplantation and triggers enhanced and prolonged immune reactions. Persistently elevated levels of MIF have been shown to override both endogenous and exogenous antiinflammatory effects of GC.MethodsTwo functional polymorphisms in the MIF gene, a −794 CATT5–8 microsatellite repeat and a −173 G/C single-nucleotide polymorphism, were analyzed in 86 patients who underwent allogeneic HSCT. We also measured MIF serum levels at different time points before and after HSCT.ResultsFrequencies of MIF high-expression -794 CATT7 containing genotypes were increased in patients with grade III-IV acute GVHD (aGVHD) (36.8%) compared with patients that did not develop aGVHD (5.8%) and patients with grade II aGVHD (0%), (p=0.0019, 0.0080 respectively). We also demonstrated that the frequencies of the MIF-794 CATT7 and -173 C containing genotypes, were significantly associated with steroid-refractory aGVHD (46.6%, 60% respectively) compared to steroid-responsive aGVHD (0%, 5.3% respectively), (p=0.0011, P=0.0007 respectively). We further showed that MIF circulating levels preceded onset of severe aGVHD.DiscussionOur findings suggest that genetically controlled high expression MIF genotypes are associated with aGVHD worsening and could serve as a biomarker enhancing identification and treatment of steroid-refractory disease. https://www.frontiersin.org/articles/10.3389/fimmu.2025.1504976/fullMIFacute GVHDsteroid-refractoryHSCTpolymorphism |
| spellingShingle | Aviran Aharon Batia Avni Daniel Louzoun Shlomo Elias Polina Stepensky Ron Ram Tsila Zuckerman Tsila Zuckerman Roberto Meza-Romero Roberto Meza-Romero Arthur A. Vandenbark Arthur A. Vandenbark Arthur A. Vandenbark Sigal Grisariu Gil Benedek Gil Benedek MIF functional polymorphisms are associated with acute GVHD progression and steroid-refractoriness Frontiers in Immunology MIF acute GVHD steroid-refractory HSCT polymorphism |
| title | MIF functional polymorphisms are associated with acute GVHD progression and steroid-refractoriness |
| title_full | MIF functional polymorphisms are associated with acute GVHD progression and steroid-refractoriness |
| title_fullStr | MIF functional polymorphisms are associated with acute GVHD progression and steroid-refractoriness |
| title_full_unstemmed | MIF functional polymorphisms are associated with acute GVHD progression and steroid-refractoriness |
| title_short | MIF functional polymorphisms are associated with acute GVHD progression and steroid-refractoriness |
| title_sort | mif functional polymorphisms are associated with acute gvhd progression and steroid refractoriness |
| topic | MIF acute GVHD steroid-refractory HSCT polymorphism |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1504976/full |
| work_keys_str_mv | AT aviranaharon miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT batiaavni miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT daniellouzoun miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT shlomoelias miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT polinastepensky miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT ronram miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT tsilazuckerman miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT tsilazuckerman miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT robertomezaromero miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT robertomezaromero miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT arthuravandenbark miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT arthuravandenbark miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT arthuravandenbark miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT sigalgrisariu miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT gilbenedek miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness AT gilbenedek miffunctionalpolymorphismsareassociatedwithacutegvhdprogressionandsteroidrefractoriness |