PMID- 34021913 OWN - NLM STAT- MEDLINE DCOM- 20211203 LR - 20220802 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 205 IP - 2 DP - 2021 Aug TI - Anti-JMH alloantibody in inherited JMH-negative patients leads to immunogenic destruction of JMH-positive RBCs. PG - 182-197 LID - 10.1111/cei.13622 [doi] AB - The clinical significance of the specific anti-John Milton Hagen (JMH) alloantibody in inherited JMH-negative patients remains unclear. During clinical blood transfusion, it is often classified as an anti-JMH autoantibody in acquired JMH-negative patients, which might further lead to the occurrence of haemolysis events. In this study, we found that the proportion of inherited JMH-negative people in the Guangzhou population was 0.41%, based on the study of 243 blood samples by flow cytometry. Gene sequencing analysis revealed two novel variants located in exon 11 (c.1348G>A, p.Ala449Thr) and exon 14 (c.1989G>T, p.Leu663Phe). Specific antigen presentation showed that JMH-positive RBCs (red blood cells) could be internalized by SEMA7A(-/-) dendritic cells (DCs) and that SEMA7A(-/-) DCs activated by the semaphorin 7a (Sema7a) protein or JMH-positive erythrocytes further induced activation of CD4(+) T cells to secrete interferon (IFN)-gamma. Transfusion of JMH-positive RBCs could lead to the production of the specific anti-JMH alloantibody in Sema7a knock-out (KO) C57 mice. After erythrocyte sensitization, complement C3 was specifically fixed, causing the destruction of JMH-positive erythrocytes. The anti-JMH alloantibody caused immunological destruction of JMH-positive erythrocytes and promoted the clearance of JMH-positive RBCs. We should be cautious when making conclusions about the clinical significance of the anti-JMH alloantibody. CI - (c) 2021 British Society for Immunology. FAU - Yuan, Zhaohu AU - Yuan Z AUID- ORCID: 0000-0002-0916-8550 AD - Department of Blood Transfusion, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. AD - Guangdong Engineering Research Center of Precise Transfusion, Guangzhou, Guangdong, China. FAU - Wei, Yaming AU - Wei Y AD - Department of Blood Transfusion, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. AD - Guangdong Engineering Research Center of Precise Transfusion, Guangzhou, Guangdong, China. FAU - Chen, Xiaojie AU - Chen X AD - Department of Blood Transfusion, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. AD - Guangdong Engineering Research Center of Precise Transfusion, Guangzhou, Guangdong, China. FAU - He, Shufei AU - He S AD - Department of Blood Transfusion, Third People's Hospital of Huizhou, Huizhou, Guangdong, China. FAU - Cai, Kui AU - Cai K AD - Department of Blood Transfusion, Foshan First People's Hospital, Foshan, Guangdong, China. FAU - Zhong, Minglu AU - Zhong M AD - Department of Blood Transfusion, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. AD - Guangdong Engineering Research Center of Precise Transfusion, Guangzhou, Guangdong, China. FAU - Huang, Huiying AU - Huang H AD - Department of Blood Transfusion, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. AD - Guangdong Engineering Research Center of Precise Transfusion, Guangzhou, Guangdong, China. FAU - Tong, Xinxin AU - Tong X AD - Department of Blood Transfusion, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. AD - Guangdong Engineering Research Center of Precise Transfusion, Guangzhou, Guangdong, China. FAU - Liu, Zhen AU - Liu Z AD - Department of Blood Transfusion, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. AD - Guangdong Engineering Research Center of Precise Transfusion, Guangzhou, Guangdong, China. FAU - Yang, Xuexin AU - Yang X AD - Department of Blood Transfusion, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. AD - Guangdong Engineering Research Center of Precise Transfusion, Guangzhou, Guangdong, China. LA - eng GR - 202002030427/Guangzhou Planned Project of Science and Technology/ GR - 201904010027/Guangzhou Planned Project of Science and Technology/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210613 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Antigens, CD) RN - 0 (Autoantibodies) RN - 0 (Complement C3) RN - 0 (Isoantibodies) RN - 0 (Semaphorins) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adult MH - Animals MH - Antibody Formation/immunology MH - Antigens, CD/*immunology MH - Autoantibodies/immunology MH - CD4-Positive T-Lymphocytes/immunology MH - Complement C3/immunology MH - Erythrocytes/*immunology MH - Female MH - Flow Cytometry/methods MH - Humans MH - Interferon-gamma/immunology MH - Isoantibodies/*immunology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Semaphorins/immunology PMC - PMC8274163 OTO - NOTNLM OT - JMH antigen (Sema7a or CD108) OT - RBCs OT - Transfusion OT - alloantibody OT - alloimmunization OT - component 3 OT - inherited JMH-negative COIS- The authors declare no conflict of interest, financial or otherwise. EDAT- 2021/05/23 06:00 MHDA- 2021/12/15 06:00 PMCR- 2022/08/01 CRDT- 2021/05/22 12:11 PHST- 2021/04/25 00:00 [revised] PHST- 2021/02/23 00:00 [received] PHST- 2021/05/11 00:00 [accepted] PHST- 2021/05/23 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/05/22 12:11 [entrez] PHST- 2022/08/01 00:00 [pmc-release] AID - CEI13622 [pii] AID - 10.1111/cei.13622 [doi] PST - ppublish SO - Clin Exp Immunol. 2021 Aug;205(2):182-197. doi: 10.1111/cei.13622. Epub 2021 Jun 13.