Early Myeloid Derived Suppressor Cells (eMDSCs) Are Associated With High Donor Myeloid Chimerism Following Haploidentical HSCT for Sickle Cell Disease
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a widely available curative option for patients with sickle cell disease (SCD). Our original non-myeloablative haplo-HSCT trial employing post-transplant (PT) cyclophosphamide had a low incidence of GVHD but had high rejection ra...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/24e70ed7cf154c4e8c2147f41d584da8 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:24e70ed7cf154c4e8c2147f41d584da8 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:24e70ed7cf154c4e8c2147f41d584da82021-12-01T18:01:56ZEarly Myeloid Derived Suppressor Cells (eMDSCs) Are Associated With High Donor Myeloid Chimerism Following Haploidentical HSCT for Sickle Cell Disease1664-322410.3389/fimmu.2021.757279https://doaj.org/article/24e70ed7cf154c4e8c2147f41d584da82021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.757279/fullhttps://doaj.org/toc/1664-3224Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a widely available curative option for patients with sickle cell disease (SCD). Our original non-myeloablative haplo-HSCT trial employing post-transplant (PT) cyclophosphamide had a low incidence of GVHD but had high rejection rates. Here, we aimed to evaluate immune reconstitution following haplo-HSCT and identify cytokines and cells associated with graft rejection/engraftment. 50 cytokines and 10 immune cell subsets were screened using multiplex-ELISA and flow cytometry, respectively, at baseline and PT-Days 30, 60, 100, and 180. We observed the most significant differences in cytokine levels between the engrafted and rejected groups at PT-Day 60, corresponding with clinical findings of secondary graft rejection. Of the 44 cytokines evaluated, plasma concentrations of 19 cytokines were different between the two groups at PT-Day 60. Factor analysis suggested two independent factors. The first factor (IL-17A, IL-10, IL-7, G-CSF, IL-2, MIP-1a, VEGF, and TGFb1 contributed significantly) was strongly associated with engraftment with OR = 2.7 (95%CI of 1.4 to 5.4), whereas the second factor (GROa and IL-18 contributed significantly) was not significantly associated with engraftment. Sufficient donor myeloid chimerism (DMC) is critical for the success of HSCT; here, we evaluated immune cells among high (H) DMC (DMC≥20%) and low (L) DMC (DMC<20%) groups along with engrafted and rejected groups. We found that early myeloid-derived suppressor cell (eMDSC) frequencies were elevated in engrafted patients and patients with HDMC at PT-Day 30 (P< 0.04 & P< 0.003, respectively). 9 of 20 patients were evaluated for the source of eMDSCs. The HDMC group had high mixed chimeric eMDSCs as compared to the LDMC group (P< 0.00001). We found a positive correlation between the frequencies of eMDSCs and Tregs at PT-Day 100 (r=0.72, P <0.0007); eMDSCs at BSL and Tregs at PT-Day 100 (r=0.63, P <0.004). Of 10 immune regulatory cells and 50 cytokines, we observed mixed chimeric eMDSCs and IL-17A, IL-10, IL-7, G-CSF, IL-2, MIP-1a, VEGF, TGFb1 as potential hits which could serve as prognostic markers in predicting allograft outcome towards engraftment following haploidentical HSCT employing post-transplant cyclophosphamide. The current findings need to be replicated and further explored in a larger cohort.Deepali K. BhatPurevdorj B. OlkhanudArunakumar GangaplaraFayaz SeifuddinMehdi PiroozniaAngélique BiancottoGiovanna FantoniCorinne PittmanBerline FrancisPradeep K. DagurAnkit SaxenaJ. Philip McCoyRuth M. PfeifferCourtney D. FitzhughFrontiers Media S.A.articledonor myeloid chimerismhaploidentical HSCTTregsIL-10sickle cell diseaseearly myeloid derived suppressor cellsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
donor myeloid chimerism haploidentical HSCT Tregs IL-10 sickle cell disease early myeloid derived suppressor cells Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
donor myeloid chimerism haploidentical HSCT Tregs IL-10 sickle cell disease early myeloid derived suppressor cells Immunologic diseases. Allergy RC581-607 Deepali K. Bhat Purevdorj B. Olkhanud Arunakumar Gangaplara Fayaz Seifuddin Mehdi Pirooznia Angélique Biancotto Giovanna Fantoni Corinne Pittman Berline Francis Pradeep K. Dagur Ankit Saxena J. Philip McCoy Ruth M. Pfeiffer Courtney D. Fitzhugh Early Myeloid Derived Suppressor Cells (eMDSCs) Are Associated With High Donor Myeloid Chimerism Following Haploidentical HSCT for Sickle Cell Disease |
| description |
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a widely available curative option for patients with sickle cell disease (SCD). Our original non-myeloablative haplo-HSCT trial employing post-transplant (PT) cyclophosphamide had a low incidence of GVHD but had high rejection rates. Here, we aimed to evaluate immune reconstitution following haplo-HSCT and identify cytokines and cells associated with graft rejection/engraftment. 50 cytokines and 10 immune cell subsets were screened using multiplex-ELISA and flow cytometry, respectively, at baseline and PT-Days 30, 60, 100, and 180. We observed the most significant differences in cytokine levels between the engrafted and rejected groups at PT-Day 60, corresponding with clinical findings of secondary graft rejection. Of the 44 cytokines evaluated, plasma concentrations of 19 cytokines were different between the two groups at PT-Day 60. Factor analysis suggested two independent factors. The first factor (IL-17A, IL-10, IL-7, G-CSF, IL-2, MIP-1a, VEGF, and TGFb1 contributed significantly) was strongly associated with engraftment with OR = 2.7 (95%CI of 1.4 to 5.4), whereas the second factor (GROa and IL-18 contributed significantly) was not significantly associated with engraftment. Sufficient donor myeloid chimerism (DMC) is critical for the success of HSCT; here, we evaluated immune cells among high (H) DMC (DMC≥20%) and low (L) DMC (DMC<20%) groups along with engrafted and rejected groups. We found that early myeloid-derived suppressor cell (eMDSC) frequencies were elevated in engrafted patients and patients with HDMC at PT-Day 30 (P< 0.04 & P< 0.003, respectively). 9 of 20 patients were evaluated for the source of eMDSCs. The HDMC group had high mixed chimeric eMDSCs as compared to the LDMC group (P< 0.00001). We found a positive correlation between the frequencies of eMDSCs and Tregs at PT-Day 100 (r=0.72, P <0.0007); eMDSCs at BSL and Tregs at PT-Day 100 (r=0.63, P <0.004). Of 10 immune regulatory cells and 50 cytokines, we observed mixed chimeric eMDSCs and IL-17A, IL-10, IL-7, G-CSF, IL-2, MIP-1a, VEGF, TGFb1 as potential hits which could serve as prognostic markers in predicting allograft outcome towards engraftment following haploidentical HSCT employing post-transplant cyclophosphamide. The current findings need to be replicated and further explored in a larger cohort. |
| format |
article |
| author |
Deepali K. Bhat Purevdorj B. Olkhanud Arunakumar Gangaplara Fayaz Seifuddin Mehdi Pirooznia Angélique Biancotto Giovanna Fantoni Corinne Pittman Berline Francis Pradeep K. Dagur Ankit Saxena J. Philip McCoy Ruth M. Pfeiffer Courtney D. Fitzhugh |
| author_facet |
Deepali K. Bhat Purevdorj B. Olkhanud Arunakumar Gangaplara Fayaz Seifuddin Mehdi Pirooznia Angélique Biancotto Giovanna Fantoni Corinne Pittman Berline Francis Pradeep K. Dagur Ankit Saxena J. Philip McCoy Ruth M. Pfeiffer Courtney D. Fitzhugh |
| author_sort |
Deepali K. Bhat |
| title |
Early Myeloid Derived Suppressor Cells (eMDSCs) Are Associated With High Donor Myeloid Chimerism Following Haploidentical HSCT for Sickle Cell Disease |
| title_short |
Early Myeloid Derived Suppressor Cells (eMDSCs) Are Associated With High Donor Myeloid Chimerism Following Haploidentical HSCT for Sickle Cell Disease |
| title_full |
Early Myeloid Derived Suppressor Cells (eMDSCs) Are Associated With High Donor Myeloid Chimerism Following Haploidentical HSCT for Sickle Cell Disease |
| title_fullStr |
Early Myeloid Derived Suppressor Cells (eMDSCs) Are Associated With High Donor Myeloid Chimerism Following Haploidentical HSCT for Sickle Cell Disease |
| title_full_unstemmed |
Early Myeloid Derived Suppressor Cells (eMDSCs) Are Associated With High Donor Myeloid Chimerism Following Haploidentical HSCT for Sickle Cell Disease |
| title_sort |
early myeloid derived suppressor cells (emdscs) are associated with high donor myeloid chimerism following haploidentical hsct for sickle cell disease |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/24e70ed7cf154c4e8c2147f41d584da8 |
| work_keys_str_mv |
AT deepalikbhat earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT purevdorjbolkhanud earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT arunakumargangaplara earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT fayazseifuddin earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT mehdipirooznia earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT angeliquebiancotto earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT giovannafantoni earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT corinnepittman earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT berlinefrancis earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT pradeepkdagur earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT ankitsaxena earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT jphilipmccoy earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT ruthmpfeiffer earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease AT courtneydfitzhugh earlymyeloidderivedsuppressorcellsemdscsareassociatedwithhighdonormyeloidchimerismfollowinghaploidenticalhsctforsicklecelldisease |
| _version_ |
1718404739737059328 |