{"title":"HNA的表型和基因分型:印度人的患病率、同种异体免疫风险和HNA不相容。","authors":"Harita Gogri, Meghana Parihar, Swati Kulkarni, Manisha Madkaikar, Jayashree Sharma, Ajit Gorakshakar","doi":"10.1159/000525654","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Antibodies to human neutrophil alloantigens (HNA) are involved in the pathophysiology of several clinical conditions including transfusion-related acute lung injury (TRALI), alloimmune and autoimmune neutropenia, and febrile nonhemolytic transfusion reactions leading to neutropenia. The cognate antigens are polymorphic structures expressed on several glycoproteins on the neutrophils, i.e., antigens HNA-1a, -1b, -1c, and -1d on Fc-γ-receptor IIIb; HNA-2 on CD177; HNA-3a and -3b on choline transporter-like protein 2; HNA-4a and -4b on CD11b/αM subunit of the αMβ2-integrin (CD11b/CD18, Mac-1, CR3); and HNA-5a and -5b on αL-subunit (CD11a) of the αLβ2 integrin (CD11a/CD18), leukocyte function associated molecule (LFA)-1. Currently, there is a lacuna of diagnostic methods for detection of HNA in India. This study aimed to determine the HNA frequencies in Indians, estimate the risk of alloimmunization, and prepare typed neutrophil panels, which can be used to detect HNA antibodies in neutropenia cases.</p><p><strong>Material and methods: </strong>EDTA blood samples were collected from random 1,054 blood donors. HNA-2 was phenotyped on fresh EDTA samples using FITC labelled monoclonal anti-CD177 by flowcytometry. HNA-1 (<i>FCGR3B</i>) genotyping was carried out by DNA sequencing and PCR-RFLP. Antigens of HNA-3 (<i>SLC44A2</i>) and HNA-5 (<i>ITGAL</i>) were genotyped by PCR-RFLP using <i>TaqαI</i> and <i>Bsp1286I</i> restriction enzymes, respectively, while HNA-4 (<i>ITGAM</i>) was genotyped by PCR-SSP.</p><p><strong>Results: </strong>Allele frequencies of <i>FCGR3B</i>*<i>01</i>, <i>FCGR3B</i>*<i>02</i>, and <i>FCGR3B</i>*<i>03</i> were found to be 0.433, 0.444, and 0.087, respectively. FCGR3B*01+*02+*03- was the most common genotype (33.78%). Ten individuals showed deficiency of FCGR3B individuals, while 23 showed hyperexpression, i.e., <i>FCGR3B</i>*<i>01+</i>*<i>02+</i>*<i>03+</i>. <i>FCGR3B</i>*<i>04</i>and *<i>05</i> occurred with a frequency of 0.002 and 0.024. HNA-2 was found to be a high frequency antigen occurring in 98.8% population. Four percent individuals showed atypical expression of CD177 on their neutrophils. Allele frequencies of <i>SLC44A2</i>*<i>01</i> and <i>SLC44A2</i>*<i>02</i>were 0.812 and 0.188, respectively, and that of <i>ITGAM</i>*<i>01</i>, <i>ITGAM</i>*<i>02</i>, <i>ITGAL</i>*<i>01</i>, and <i>ITGAL</i>*<i>02</i> were 0.9546, 0.0454, 0.2372, and 0.7628, respectively.</p><p><strong>Conclusion: </strong>This is the first study in India to report the frequencies of HNA among blood donors. Typed neutrophil panels identified in the present study will enable us to investigate suspected cases of immune neutropenia in future.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/3a/tmh-0050-0030.PMC9911994.pdf","citationCount":"1","resultStr":"{\"title\":\"Phenotyping and Genotyping of HNA: Prevalence, Risk of Alloimmunization, and HNA Incompatibilities in Indians.\",\"authors\":\"Harita Gogri, Meghana Parihar, Swati Kulkarni, Manisha Madkaikar, Jayashree Sharma, Ajit Gorakshakar\",\"doi\":\"10.1159/000525654\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Antibodies to human neutrophil alloantigens (HNA) are involved in the pathophysiology of several clinical conditions including transfusion-related acute lung injury (TRALI), alloimmune and autoimmune neutropenia, and febrile nonhemolytic transfusion reactions leading to neutropenia. The cognate antigens are polymorphic structures expressed on several glycoproteins on the neutrophils, i.e., antigens HNA-1a, -1b, -1c, and -1d on Fc-γ-receptor IIIb; HNA-2 on CD177; HNA-3a and -3b on choline transporter-like protein 2; HNA-4a and -4b on CD11b/αM subunit of the αMβ2-integrin (CD11b/CD18, Mac-1, CR3); and HNA-5a and -5b on αL-subunit (CD11a) of the αLβ2 integrin (CD11a/CD18), leukocyte function associated molecule (LFA)-1. Currently, there is a lacuna of diagnostic methods for detection of HNA in India. This study aimed to determine the HNA frequencies in Indians, estimate the risk of alloimmunization, and prepare typed neutrophil panels, which can be used to detect HNA antibodies in neutropenia cases.</p><p><strong>Material and methods: </strong>EDTA blood samples were collected from random 1,054 blood donors. HNA-2 was phenotyped on fresh EDTA samples using FITC labelled monoclonal anti-CD177 by flowcytometry. HNA-1 (<i>FCGR3B</i>) genotyping was carried out by DNA sequencing and PCR-RFLP. Antigens of HNA-3 (<i>SLC44A2</i>) and HNA-5 (<i>ITGAL</i>) were genotyped by PCR-RFLP using <i>TaqαI</i> and <i>Bsp1286I</i> restriction enzymes, respectively, while HNA-4 (<i>ITGAM</i>) was genotyped by PCR-SSP.</p><p><strong>Results: </strong>Allele frequencies of <i>FCGR3B</i>*<i>01</i>, <i>FCGR3B</i>*<i>02</i>, and <i>FCGR3B</i>*<i>03</i> were found to be 0.433, 0.444, and 0.087, respectively. FCGR3B*01+*02+*03- was the most common genotype (33.78%). Ten individuals showed deficiency of FCGR3B individuals, while 23 showed hyperexpression, i.e., <i>FCGR3B</i>*<i>01+</i>*<i>02+</i>*<i>03+</i>. <i>FCGR3B</i>*<i>04</i>and *<i>05</i> occurred with a frequency of 0.002 and 0.024. HNA-2 was found to be a high frequency antigen occurring in 98.8% population. Four percent individuals showed atypical expression of CD177 on their neutrophils. Allele frequencies of <i>SLC44A2</i>*<i>01</i> and <i>SLC44A2</i>*<i>02</i>were 0.812 and 0.188, respectively, and that of <i>ITGAM</i>*<i>01</i>, <i>ITGAM</i>*<i>02</i>, <i>ITGAL</i>*<i>01</i>, and <i>ITGAL</i>*<i>02</i> were 0.9546, 0.0454, 0.2372, and 0.7628, respectively.</p><p><strong>Conclusion: </strong>This is the first study in India to report the frequencies of HNA among blood donors. Typed neutrophil panels identified in the present study will enable us to investigate suspected cases of immune neutropenia in future.</p>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2023-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/3a/tmh-0050-0030.PMC9911994.pdf\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000525654\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000525654","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Phenotyping and Genotyping of HNA: Prevalence, Risk of Alloimmunization, and HNA Incompatibilities in Indians.
Background: Antibodies to human neutrophil alloantigens (HNA) are involved in the pathophysiology of several clinical conditions including transfusion-related acute lung injury (TRALI), alloimmune and autoimmune neutropenia, and febrile nonhemolytic transfusion reactions leading to neutropenia. The cognate antigens are polymorphic structures expressed on several glycoproteins on the neutrophils, i.e., antigens HNA-1a, -1b, -1c, and -1d on Fc-γ-receptor IIIb; HNA-2 on CD177; HNA-3a and -3b on choline transporter-like protein 2; HNA-4a and -4b on CD11b/αM subunit of the αMβ2-integrin (CD11b/CD18, Mac-1, CR3); and HNA-5a and -5b on αL-subunit (CD11a) of the αLβ2 integrin (CD11a/CD18), leukocyte function associated molecule (LFA)-1. Currently, there is a lacuna of diagnostic methods for detection of HNA in India. This study aimed to determine the HNA frequencies in Indians, estimate the risk of alloimmunization, and prepare typed neutrophil panels, which can be used to detect HNA antibodies in neutropenia cases.
Material and methods: EDTA blood samples were collected from random 1,054 blood donors. HNA-2 was phenotyped on fresh EDTA samples using FITC labelled monoclonal anti-CD177 by flowcytometry. HNA-1 (FCGR3B) genotyping was carried out by DNA sequencing and PCR-RFLP. Antigens of HNA-3 (SLC44A2) and HNA-5 (ITGAL) were genotyped by PCR-RFLP using TaqαI and Bsp1286I restriction enzymes, respectively, while HNA-4 (ITGAM) was genotyped by PCR-SSP.
Results: Allele frequencies of FCGR3B*01, FCGR3B*02, and FCGR3B*03 were found to be 0.433, 0.444, and 0.087, respectively. FCGR3B*01+*02+*03- was the most common genotype (33.78%). Ten individuals showed deficiency of FCGR3B individuals, while 23 showed hyperexpression, i.e., FCGR3B*01+*02+*03+. FCGR3B*04and *05 occurred with a frequency of 0.002 and 0.024. HNA-2 was found to be a high frequency antigen occurring in 98.8% population. Four percent individuals showed atypical expression of CD177 on their neutrophils. Allele frequencies of SLC44A2*01 and SLC44A2*02were 0.812 and 0.188, respectively, and that of ITGAM*01, ITGAM*02, ITGAL*01, and ITGAL*02 were 0.9546, 0.0454, 0.2372, and 0.7628, respectively.
Conclusion: This is the first study in India to report the frequencies of HNA among blood donors. Typed neutrophil panels identified in the present study will enable us to investigate suspected cases of immune neutropenia in future.
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Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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