{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pal M"],"funding":["NHLBI NIH HHS"],"pagination":["269-280"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7820872"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["137(2)"],"pubmed_abstract":["Red blood cell alloimmunization remains a barrier for safe and effective transfusions in sickle cell disease (SCD), but the associated risk factors remain largely unknown. Intravascular hemolysis, a hallmark of SCD, results in the release of heme with potent immunomodulatory activity, although its effect on SCD humoral response, specifically alloimmunization, remains unclear. Here, we found that cell-free heme suppresses human B-cell plasmablast and plasma cell differentiation by inhibiting the DOCK8/STAT3 signaling pathway, which is critical for B-cell activation, as well as by upregulating heme oxygenase 1 (HO-1) through its enzymatic byproducts, carbon monoxide and biliverdin. Whereas nonalloimmunized SCD B cells were inhibited by exogenous heme, B cells from the alloimmunized group wer"],"journal":["Blood"],"pubmed_title":["Hemolysis inhibits humoral B-cell responses and modulates alloimmunization risk in patients with sickle cell disease."],"pmcid":["PMC7820872"],"funding_grant_id":["P01 HL149626","R01 HL130139"],"pubmed_authors":["Liu Y","Shi PA","Manwani D","Minniti C","Wang R","Lobo CA","Mitchell WB","Bao W","An X","Zhong H","Yazdanbakhsh K","Pal M"],"additional_accession":[]},"is_claimable":false,"name":"Hemolysis inhibits humoral B-cell responses and modulates alloimmunization risk in patients with sickle cell disease.","description":"Red blood cell alloimmunization remains a barrier for safe and effective transfusions in sickle cell disease (SCD), but the associated risk factors remain largely unknown. Intravascular hemolysis, a hallmark of SCD, results in the release of heme with potent immunomodulatory activity, although its effect on SCD humoral response, specifically alloimmunization, remains unclear. Here, we found that cell-free heme suppresses human B-cell plasmablast and plasma cell differentiation by inhibiting the DOCK8/STAT3 signaling pathway, which is critical for B-cell activation, as well as by upregulating heme oxygenase 1 (HO-1) through its enzymatic byproducts, carbon monoxide and biliverdin. Whereas nonalloimmunized SCD B cells were inhibited by exogenous heme, B cells from the alloimmunized group wer","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jan","modification":"2025-04-18T15:12:57.342Z","creation":"2025-04-07T01:47:01.57Z"},"accession":"S-EPMC7820872","cross_references":{"pubmed":["33152749"],"doi":["10.1182/blood.2020008511"]}}