HLA antibodies in fetal and neonatal alloimmune thrombocytopenia
Background Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by antibodies against human platelet antigens (HPA). However, in many cases that meet clinical criteria for the condition, maternal sera do not have HPA antibodies. In studies examining whether human leukocyte antigen (HLA)...
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| Veröffentlicht in: | Transfusion (Philadelphia, Pa.) Pa.), 2023-06, Vol.63 (6), p.1141-1149 |
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| container_title | Transfusion (Philadelphia, Pa.) |
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| creator | Colvin, Zachary A. Schiller, Jennifer Tsaih, Shirng‐Wern Sharma, Ruchika Grace, Rachael F. McIntosh, Jennifer J. Curtis, Brian R. |
| description | Background
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by antibodies against human platelet antigens (HPA). However, in many cases that meet clinical criteria for the condition, maternal sera do not have HPA antibodies. In studies examining whether human leukocyte antigen (HLA) antibodies cause FNAIT, the results are limited and inconclusive. This study sought to examine whether clinically suspected FNAIT cases with absent maternal HPA antibodies had different HLA antibody strength and specificity compared to controls.
Study Design and Methods
A retrospective case–control study assessed class I HLA antibody strength and specificity in cases submitted for testing to Versiti, Wisconsin. There were 813 cases that met initial screening criteria, but written consent could only be obtained for 50. After review of medical records and expert panel review, 31 cases with clinical criteria of FNAIT and maternal HLA but not HPA antibodies were included. Each case was matched for maternal age, gestational age at delivery, parity, and race/ethnicity to two controls from unaffected pregnancies that had maternal serum HLA antibodies.
Results
FNAIT cases were found to have both significantly higher HLA antibody strength, measured by mean fluorescence index (MFI), and broader HLA antibody specificity at antigen epitope level, compared to matched controls (p |
| doi_str_mv | 10.1111/trf.17342 |
| format | Article |
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Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by antibodies against human platelet antigens (HPA). However, in many cases that meet clinical criteria for the condition, maternal sera do not have HPA antibodies. In studies examining whether human leukocyte antigen (HLA) antibodies cause FNAIT, the results are limited and inconclusive. This study sought to examine whether clinically suspected FNAIT cases with absent maternal HPA antibodies had different HLA antibody strength and specificity compared to controls.
Study Design and Methods
A retrospective case–control study assessed class I HLA antibody strength and specificity in cases submitted for testing to Versiti, Wisconsin. There were 813 cases that met initial screening criteria, but written consent could only be obtained for 50. After review of medical records and expert panel review, 31 cases with clinical criteria of FNAIT and maternal HLA but not HPA antibodies were included. Each case was matched for maternal age, gestational age at delivery, parity, and race/ethnicity to two controls from unaffected pregnancies that had maternal serum HLA antibodies.
Results
FNAIT cases were found to have both significantly higher HLA antibody strength, measured by mean fluorescence index (MFI), and broader HLA antibody specificity at antigen epitope level, compared to matched controls (p < .001). p‐values remained significant after controlling for parity and gestational age at delivery.
Discussion
Additional studies are needed to further examine whether the strong HLA antibodies identified in HPA‐antibody‐negative cases directly cause neonatal thrombocytopenia and whether prenatal treatment may be warranted in select cases to prevent recurrence.</description><identifier>ISSN: 0041-1132</identifier><identifier>EISSN: 1537-2995</identifier><identifier>DOI: 10.1111/trf.17342</identifier><identifier>PMID: 37038316</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Age ; Antibodies ; Antigens ; Antigens, Human Platelet ; Case-Control Studies ; Criteria ; Epitopes ; Female ; Fetuses ; Fluorescence ; FNAIT ; Gestational age ; Histocompatibility antigen HLA ; HLA ; HLA Antigens ; Humans ; Infant, Newborn ; Medical records ; Minority & ethnic groups ; neonatal ; Neonates ; Parity ; Pregnancy ; Prenatal Care ; Retrospective Studies ; Thrombocytopenia ; Thrombocytopenia, Neonatal Alloimmune</subject><ispartof>Transfusion (Philadelphia, Pa.), 2023-06, Vol.63 (6), p.1141-1149</ispartof><rights>2023 AABB.</rights><rights>2023 AABB</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-2ead2b240c2f3424acb113756eac9afab15f4964e2f25449ccd27d5093f9f8d83</citedby><cites>FETCH-LOGICAL-c3532-2ead2b240c2f3424acb113756eac9afab15f4964e2f25449ccd27d5093f9f8d83</cites><orcidid>0000-0001-7302-0449 ; 0000-0003-3643-0195 ; 0000-0002-0299-9589 ; 0000-0002-3157-2445 ; 0000-0001-9553-9081 ; 0000-0002-9836-4659</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Ftrf.17342$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Ftrf.17342$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27907,27908,45557,45558</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37038316$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Colvin, Zachary A.</creatorcontrib><creatorcontrib>Schiller, Jennifer</creatorcontrib><creatorcontrib>Tsaih, Shirng‐Wern</creatorcontrib><creatorcontrib>Sharma, Ruchika</creatorcontrib><creatorcontrib>Grace, Rachael F.</creatorcontrib><creatorcontrib>McIntosh, Jennifer J.</creatorcontrib><creatorcontrib>Curtis, Brian R.</creatorcontrib><title>HLA antibodies in fetal and neonatal alloimmune thrombocytopenia</title><title>Transfusion (Philadelphia, Pa.)</title><addtitle>Transfusion</addtitle><description>Background
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by antibodies against human platelet antigens (HPA). However, in many cases that meet clinical criteria for the condition, maternal sera do not have HPA antibodies. In studies examining whether human leukocyte antigen (HLA) antibodies cause FNAIT, the results are limited and inconclusive. This study sought to examine whether clinically suspected FNAIT cases with absent maternal HPA antibodies had different HLA antibody strength and specificity compared to controls.
Study Design and Methods
A retrospective case–control study assessed class I HLA antibody strength and specificity in cases submitted for testing to Versiti, Wisconsin. There were 813 cases that met initial screening criteria, but written consent could only be obtained for 50. After review of medical records and expert panel review, 31 cases with clinical criteria of FNAIT and maternal HLA but not HPA antibodies were included. Each case was matched for maternal age, gestational age at delivery, parity, and race/ethnicity to two controls from unaffected pregnancies that had maternal serum HLA antibodies.
Results
FNAIT cases were found to have both significantly higher HLA antibody strength, measured by mean fluorescence index (MFI), and broader HLA antibody specificity at antigen epitope level, compared to matched controls (p < .001). p‐values remained significant after controlling for parity and gestational age at delivery.
Discussion
Additional studies are needed to further examine whether the strong HLA antibodies identified in HPA‐antibody‐negative cases directly cause neonatal thrombocytopenia and whether prenatal treatment may be warranted in select cases to prevent recurrence.</description><subject>Age</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Antigens, Human Platelet</subject><subject>Case-Control Studies</subject><subject>Criteria</subject><subject>Epitopes</subject><subject>Female</subject><subject>Fetuses</subject><subject>Fluorescence</subject><subject>FNAIT</subject><subject>Gestational age</subject><subject>Histocompatibility antigen HLA</subject><subject>HLA</subject><subject>HLA Antigens</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Medical records</subject><subject>Minority & ethnic groups</subject><subject>neonatal</subject><subject>Neonates</subject><subject>Parity</subject><subject>Pregnancy</subject><subject>Prenatal Care</subject><subject>Retrospective Studies</subject><subject>Thrombocytopenia</subject><subject>Thrombocytopenia, Neonatal Alloimmune</subject><issn>0041-1132</issn><issn>1537-2995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFLwzAUx4Mobk4PfgEpeNFDt-QlWZubYzgnDASZ55CmCWa0zWxaZN_euE0Pgu_yeI8ff_78ELomeEziTLrWjklGGZygIeE0S0EIfoqGGDOSEkJhgC5C2GCMQWByjgY0wzSnZDpED8vVLFFN5wpfOhMS1yTWdKqKvzJpjG_U_qgq7-q6b0zSvbe-LrzedX5rGqcu0ZlVVTBXxz1Cb4vH9XyZrl6enuezVaopp5CCUSUUwLAGG4sypYtYLONTo7RQVhWEWyamzIAFzpjQuoSs5FhQK2xe5nSE7g6529Z_9CZ0snZBm6pSsWUfJGRC5MDznEb09g-68X3bxHYScmA8i6p4pO4PlG59CK2xctu6WrU7SbD81iqjVrnXGtmbY2Jf1Kb8JX88RmByAD5dZXb_J8n16-IQ-QUskYBD</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Colvin, Zachary A.</creator><creator>Schiller, Jennifer</creator><creator>Tsaih, Shirng‐Wern</creator><creator>Sharma, Ruchika</creator><creator>Grace, Rachael F.</creator><creator>McIntosh, Jennifer J.</creator><creator>Curtis, Brian R.</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7302-0449</orcidid><orcidid>https://orcid.org/0000-0003-3643-0195</orcidid><orcidid>https://orcid.org/0000-0002-0299-9589</orcidid><orcidid>https://orcid.org/0000-0002-3157-2445</orcidid><orcidid>https://orcid.org/0000-0001-9553-9081</orcidid><orcidid>https://orcid.org/0000-0002-9836-4659</orcidid></search><sort><creationdate>202306</creationdate><title>HLA antibodies in fetal and neonatal alloimmune thrombocytopenia</title><author>Colvin, Zachary A. ; Schiller, Jennifer ; Tsaih, Shirng‐Wern ; Sharma, Ruchika ; Grace, Rachael F. ; McIntosh, Jennifer J. ; Curtis, Brian R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3532-2ead2b240c2f3424acb113756eac9afab15f4964e2f25449ccd27d5093f9f8d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Age</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Antigens, Human Platelet</topic><topic>Case-Control Studies</topic><topic>Criteria</topic><topic>Epitopes</topic><topic>Female</topic><topic>Fetuses</topic><topic>Fluorescence</topic><topic>FNAIT</topic><topic>Gestational age</topic><topic>Histocompatibility antigen HLA</topic><topic>HLA</topic><topic>HLA Antigens</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Medical records</topic><topic>Minority & ethnic groups</topic><topic>neonatal</topic><topic>Neonates</topic><topic>Parity</topic><topic>Pregnancy</topic><topic>Prenatal Care</topic><topic>Retrospective Studies</topic><topic>Thrombocytopenia</topic><topic>Thrombocytopenia, Neonatal Alloimmune</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Colvin, Zachary A.</creatorcontrib><creatorcontrib>Schiller, Jennifer</creatorcontrib><creatorcontrib>Tsaih, Shirng‐Wern</creatorcontrib><creatorcontrib>Sharma, Ruchika</creatorcontrib><creatorcontrib>Grace, Rachael F.</creatorcontrib><creatorcontrib>McIntosh, Jennifer J.</creatorcontrib><creatorcontrib>Curtis, Brian R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transfusion (Philadelphia, Pa.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Colvin, Zachary A.</au><au>Schiller, Jennifer</au><au>Tsaih, Shirng‐Wern</au><au>Sharma, Ruchika</au><au>Grace, Rachael F.</au><au>McIntosh, Jennifer J.</au><au>Curtis, Brian R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HLA antibodies in fetal and neonatal alloimmune thrombocytopenia</atitle><jtitle>Transfusion (Philadelphia, Pa.)</jtitle><addtitle>Transfusion</addtitle><date>2023-06</date><risdate>2023</risdate><volume>63</volume><issue>6</issue><spage>1141</spage><epage>1149</epage><pages>1141-1149</pages><issn>0041-1132</issn><eissn>1537-2995</eissn><abstract>Background
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by antibodies against human platelet antigens (HPA). However, in many cases that meet clinical criteria for the condition, maternal sera do not have HPA antibodies. In studies examining whether human leukocyte antigen (HLA) antibodies cause FNAIT, the results are limited and inconclusive. This study sought to examine whether clinically suspected FNAIT cases with absent maternal HPA antibodies had different HLA antibody strength and specificity compared to controls.
Study Design and Methods
A retrospective case–control study assessed class I HLA antibody strength and specificity in cases submitted for testing to Versiti, Wisconsin. There were 813 cases that met initial screening criteria, but written consent could only be obtained for 50. After review of medical records and expert panel review, 31 cases with clinical criteria of FNAIT and maternal HLA but not HPA antibodies were included. Each case was matched for maternal age, gestational age at delivery, parity, and race/ethnicity to two controls from unaffected pregnancies that had maternal serum HLA antibodies.
Results
FNAIT cases were found to have both significantly higher HLA antibody strength, measured by mean fluorescence index (MFI), and broader HLA antibody specificity at antigen epitope level, compared to matched controls (p < .001). p‐values remained significant after controlling for parity and gestational age at delivery.
Discussion
Additional studies are needed to further examine whether the strong HLA antibodies identified in HPA‐antibody‐negative cases directly cause neonatal thrombocytopenia and whether prenatal treatment may be warranted in select cases to prevent recurrence.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>37038316</pmid><doi>10.1111/trf.17342</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-7302-0449</orcidid><orcidid>https://orcid.org/0000-0003-3643-0195</orcidid><orcidid>https://orcid.org/0000-0002-0299-9589</orcidid><orcidid>https://orcid.org/0000-0002-3157-2445</orcidid><orcidid>https://orcid.org/0000-0001-9553-9081</orcidid><orcidid>https://orcid.org/0000-0002-9836-4659</orcidid></addata></record> |
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| ispartof | Transfusion (Philadelphia, Pa.), 2023-06, Vol.63 (6), p.1141-1149 |
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| subjects | Age Antibodies Antigens Antigens, Human Platelet Case-Control Studies Criteria Epitopes Female Fetuses Fluorescence FNAIT Gestational age Histocompatibility antigen HLA HLA HLA Antigens Humans Infant, Newborn Medical records Minority & ethnic groups neonatal Neonates Parity Pregnancy Prenatal Care Retrospective Studies Thrombocytopenia Thrombocytopenia, Neonatal Alloimmune |
| title | HLA antibodies in fetal and neonatal alloimmune thrombocytopenia |
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