{"doi":"10.3389/fimmu.2021.757279","title":"Early Myeloid Derived Suppressor Cells (eMDSCs) Are Associated With High Donor Myeloid Chimerism Following Haploidentical HSCT for Sickle Cell Disease","abstract":"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.","journal":"Frontiers in Immunology","year":2021,"id":184696,"datarank":0.5318063184953573,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.15907032102715718,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.15907032102715718,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":7,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00977691"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":536638,"name":"Purevdorj B. Olkhanud","orcid":"0000-0002-3336-376X","position":1,"is_corresponding":false},{"id":385521,"name":"Arunakumar Gangaplara","orcid":"0000-0001-6307-9391","position":2,"is_corresponding":false},{"id":268695,"name":"Fayaz Seifuddin","orcid":"0000-0003-3357-7888","position":3,"is_corresponding":false},{"id":268694,"name":"Mehdi Pirooznia","orcid":"0000-0002-4210-6458","position":4,"is_corresponding":false},{"id":243008,"name":"Angélique Biancotto","orcid":"0000-0003-2271-009X","position":5,"is_corresponding":false},{"id":243005,"name":"Giovanna Fantoni","orcid":"0000-0002-1920-587X","position":6,"is_corresponding":false},{"id":539259,"name":"Corinne A. Pittman","orcid":"0009-0007-3135-3465","position":7,"is_corresponding":false},{"id":740597,"name":"Berline Francis","orcid":null,"position":8,"is_corresponding":false},{"id":271933,"name":"Pradeep K. Dagur","orcid":"0000-0002-4491-0853","position":9,"is_corresponding":false},{"id":407481,"name":"Ankit Saxena","orcid":"0000-0001-5305-3681","position":10,"is_corresponding":false},{"id":271934,"name":"J. Philip McCoy","orcid":"0000-0002-8118-5275","position":11,"is_corresponding":false},{"id":282490,"name":"Ruth M. Pfeiffer","orcid":"0000-0001-7791-2698","position":12,"is_corresponding":false},{"id":314732,"name":"Courtney D. Fitzhugh","orcid":"0000-0002-5306-7167","position":13,"is_corresponding":false},{"id":740596,"name":"Deepali K. Bhat","orcid":null,"position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-18T23:48:30.970730Z","pmid":"34917079","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}