Value of Isolated IgA Anti-[beta]2-Glycoprotein I Positivity in the Diagnosis of the Antiphospholipid Syndrome
Objective To examine the prevalence of isolated IgA anti-[beta]2-glycoprotein I (anti-[beta]2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of [beta]2GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient g...
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| creator | Murthy, Vijaya Willis, Rohan Romay-Penabad, Zurina Ruiz-Limon, Patricia Martinez-Martinez, Laura A Jatwani, Shraddha Jajoria, Praveen Seif, Alan Alarcon, Graciela S Papalardo, Elizabeth Liu, Jigna Vila, Luis M McGwin, Gerald McNearney, Terry A Maganti, Rashmi Sunkureddi, Prashanth Parekh, Trisha Tarantino, Michael Akhter, Ehtisham Fang, Hong Gonzalez, Emilio B Binder, Walter R Norman, Gary L Shums, Zakera Teodorescu, Marius Reveille, John D Petri, Michelle Pierangeli, Silvia S |
| description | Objective To examine the prevalence of isolated IgA anti-[beta]2-glycoprotein I (anti-[beta]2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of [beta]2GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-[beta]2GPI in a mouse model of thrombosis. Methods Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-[beta]2GPI titers and binding to domain IV/V of [beta]2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-[beta]2GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity. Results A total of 198 patients were found to be positive for IgA anti-[beta]2GPI isotype, and 57 patients were positive exclusively for IgA anti-[beta]2GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-[beta]2GPI-positive serum samples reacted with domain IV/V of anti-[beta]2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-[beta]2GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-[beta]2GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-[beta]2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. Conclusion Isolated IgA anti-[beta]2GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-[beta]2GPI antibodies directed to domain IV/V of [beta]2GPI represent an important subgroup of clinically relevant antiphospholipids. [PUBLICATION AB |
| doi_str_mv | 10.1002/art.38131 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_journals_1462012045</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3138907981</sourcerecordid><originalsourceid>FETCH-proquest_journals_14620120453</originalsourceid><addsrcrecordid>eNqNTE2LwjAQDbKCsnrwHwzsue4ktVWP4q5ub4LiRUSijRrJJrWZCv33prDed2CY9zHvMTbgOOSI4lOWNIwnPOYt1hWxSKNEYPL2wnzKO6zv_Q3DTMeYYtJlditNpcCdIfPOSFI5ZJcZzCzpaHdUJPciWpr65IrSkdIWMlg5r0k_NNUQOF0VfGl5sUH1TU8jNPHi6nxYowudw7q2eel-VY-1z9J41f-77-xj8b2Z_0Sh_l4pT4ebq0obrAMfpQK5wFES_-_rCWesT08</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1462012045</pqid></control><display><type>article</type><title>Value of Isolated IgA Anti-[beta]2-Glycoprotein I Positivity in the Diagnosis of the Antiphospholipid Syndrome</title><source>Access via Wiley Online Library</source><creator>Murthy, Vijaya ; Willis, Rohan ; Romay-Penabad, Zurina ; Ruiz-Limon, Patricia ; Martinez-Martinez, Laura A ; Jatwani, Shraddha ; Jajoria, Praveen ; Seif, Alan ; Alarcon, Graciela S ; Papalardo, Elizabeth ; Liu, Jigna ; Vila, Luis M ; McGwin, Gerald ; McNearney, Terry A ; Maganti, Rashmi ; Sunkureddi, Prashanth ; Parekh, Trisha ; Tarantino, Michael ; Akhter, Ehtisham ; Fang, Hong ; Gonzalez, Emilio B ; Binder, Walter R ; Norman, Gary L ; Shums, Zakera ; Teodorescu, Marius ; Reveille, John D ; Petri, Michelle ; Pierangeli, Silvia S</creator><creatorcontrib>Murthy, Vijaya ; Willis, Rohan ; Romay-Penabad, Zurina ; Ruiz-Limon, Patricia ; Martinez-Martinez, Laura A ; Jatwani, Shraddha ; Jajoria, Praveen ; Seif, Alan ; Alarcon, Graciela S ; Papalardo, Elizabeth ; Liu, Jigna ; Vila, Luis M ; McGwin, Gerald ; McNearney, Terry A ; Maganti, Rashmi ; Sunkureddi, Prashanth ; Parekh, Trisha ; Tarantino, Michael ; Akhter, Ehtisham ; Fang, Hong ; Gonzalez, Emilio B ; Binder, Walter R ; Norman, Gary L ; Shums, Zakera ; Teodorescu, Marius ; Reveille, John D ; Petri, Michelle ; Pierangeli, Silvia S</creatorcontrib><description>Objective To examine the prevalence of isolated IgA anti-[beta]2-glycoprotein I (anti-[beta]2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of [beta]2GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-[beta]2GPI in a mouse model of thrombosis. Methods Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-[beta]2GPI titers and binding to domain IV/V of [beta]2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-[beta]2GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity. Results A total of 198 patients were found to be positive for IgA anti-[beta]2GPI isotype, and 57 patients were positive exclusively for IgA anti-[beta]2GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-[beta]2GPI-positive serum samples reacted with domain IV/V of anti-[beta]2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-[beta]2GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-[beta]2GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-[beta]2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. Conclusion Isolated IgA anti-[beta]2GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-[beta]2GPI antibodies directed to domain IV/V of [beta]2GPI represent an important subgroup of clinically relevant antiphospholipids. [PUBLICATION ABSTRACT]</description><identifier>ISSN: 2326-5191</identifier><identifier>EISSN: 2326-5205</identifier><identifier>DOI: 10.1002/art.38131</identifier><identifier>CODEN: ARHEAW</identifier><language>eng</language><publisher>Atlanta: Wiley Subscription Services, Inc</publisher><subject>Beta ; Lupus ; Thrombosis</subject><ispartof>Arthritis & rheumatology (Hoboken, N.J.), 2013-12, Vol.65 (12), p.3186</ispartof><rights>Copyright © 2013 by the American College of Rheumatology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids></links><search><creatorcontrib>Murthy, Vijaya</creatorcontrib><creatorcontrib>Willis, Rohan</creatorcontrib><creatorcontrib>Romay-Penabad, Zurina</creatorcontrib><creatorcontrib>Ruiz-Limon, Patricia</creatorcontrib><creatorcontrib>Martinez-Martinez, Laura A</creatorcontrib><creatorcontrib>Jatwani, Shraddha</creatorcontrib><creatorcontrib>Jajoria, Praveen</creatorcontrib><creatorcontrib>Seif, Alan</creatorcontrib><creatorcontrib>Alarcon, Graciela S</creatorcontrib><creatorcontrib>Papalardo, Elizabeth</creatorcontrib><creatorcontrib>Liu, Jigna</creatorcontrib><creatorcontrib>Vila, Luis M</creatorcontrib><creatorcontrib>McGwin, Gerald</creatorcontrib><creatorcontrib>McNearney, Terry A</creatorcontrib><creatorcontrib>Maganti, Rashmi</creatorcontrib><creatorcontrib>Sunkureddi, Prashanth</creatorcontrib><creatorcontrib>Parekh, Trisha</creatorcontrib><creatorcontrib>Tarantino, Michael</creatorcontrib><creatorcontrib>Akhter, Ehtisham</creatorcontrib><creatorcontrib>Fang, Hong</creatorcontrib><creatorcontrib>Gonzalez, Emilio B</creatorcontrib><creatorcontrib>Binder, Walter R</creatorcontrib><creatorcontrib>Norman, Gary L</creatorcontrib><creatorcontrib>Shums, Zakera</creatorcontrib><creatorcontrib>Teodorescu, Marius</creatorcontrib><creatorcontrib>Reveille, John D</creatorcontrib><creatorcontrib>Petri, Michelle</creatorcontrib><creatorcontrib>Pierangeli, Silvia S</creatorcontrib><title>Value of Isolated IgA Anti-[beta]2-Glycoprotein I Positivity in the Diagnosis of the Antiphospholipid Syndrome</title><title>Arthritis & rheumatology (Hoboken, N.J.)</title><description>Objective To examine the prevalence of isolated IgA anti-[beta]2-glycoprotein I (anti-[beta]2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of [beta]2GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-[beta]2GPI in a mouse model of thrombosis. Methods Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-[beta]2GPI titers and binding to domain IV/V of [beta]2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-[beta]2GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity. Results A total of 198 patients were found to be positive for IgA anti-[beta]2GPI isotype, and 57 patients were positive exclusively for IgA anti-[beta]2GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-[beta]2GPI-positive serum samples reacted with domain IV/V of anti-[beta]2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-[beta]2GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-[beta]2GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-[beta]2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. Conclusion Isolated IgA anti-[beta]2GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-[beta]2GPI antibodies directed to domain IV/V of [beta]2GPI represent an important subgroup of clinically relevant antiphospholipids. [PUBLICATION ABSTRACT]</description><subject>Beta</subject><subject>Lupus</subject><subject>Thrombosis</subject><issn>2326-5191</issn><issn>2326-5205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqNTE2LwjAQDbKCsnrwHwzsue4ktVWP4q5ub4LiRUSijRrJJrWZCv33prDed2CY9zHvMTbgOOSI4lOWNIwnPOYt1hWxSKNEYPL2wnzKO6zv_Q3DTMeYYtJlditNpcCdIfPOSFI5ZJcZzCzpaHdUJPciWpr65IrSkdIWMlg5r0k_NNUQOF0VfGl5sUH1TU8jNPHi6nxYowudw7q2eel-VY-1z9J41f-77-xj8b2Z_0Sh_l4pT4ebq0obrAMfpQK5wFES_-_rCWesT08</recordid><startdate>20131201</startdate><enddate>20131201</enddate><creator>Murthy, Vijaya</creator><creator>Willis, Rohan</creator><creator>Romay-Penabad, Zurina</creator><creator>Ruiz-Limon, Patricia</creator><creator>Martinez-Martinez, Laura A</creator><creator>Jatwani, Shraddha</creator><creator>Jajoria, Praveen</creator><creator>Seif, Alan</creator><creator>Alarcon, Graciela S</creator><creator>Papalardo, Elizabeth</creator><creator>Liu, Jigna</creator><creator>Vila, Luis M</creator><creator>McGwin, Gerald</creator><creator>McNearney, Terry A</creator><creator>Maganti, Rashmi</creator><creator>Sunkureddi, Prashanth</creator><creator>Parekh, Trisha</creator><creator>Tarantino, Michael</creator><creator>Akhter, Ehtisham</creator><creator>Fang, Hong</creator><creator>Gonzalez, Emilio B</creator><creator>Binder, Walter R</creator><creator>Norman, Gary L</creator><creator>Shums, Zakera</creator><creator>Teodorescu, Marius</creator><creator>Reveille, John D</creator><creator>Petri, Michelle</creator><creator>Pierangeli, Silvia S</creator><general>Wiley Subscription Services, Inc</general><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>20131201</creationdate><title>Value of Isolated IgA Anti-[beta]2-Glycoprotein I Positivity in the Diagnosis of the Antiphospholipid Syndrome</title><author>Murthy, Vijaya ; 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Methods Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-[beta]2GPI titers and binding to domain IV/V of [beta]2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-[beta]2GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity. Results A total of 198 patients were found to be positive for IgA anti-[beta]2GPI isotype, and 57 patients were positive exclusively for IgA anti-[beta]2GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-[beta]2GPI-positive serum samples reacted with domain IV/V of anti-[beta]2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-[beta]2GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-[beta]2GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-[beta]2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. Conclusion Isolated IgA anti-[beta]2GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-[beta]2GPI antibodies directed to domain IV/V of [beta]2GPI represent an important subgroup of clinically relevant antiphospholipids. [PUBLICATION ABSTRACT]</abstract><cop>Atlanta</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/art.38131</doi></addata></record> |
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| subjects | Beta Lupus Thrombosis |
| title | Value of Isolated IgA Anti-[beta]2-Glycoprotein I Positivity in the Diagnosis of the Antiphospholipid Syndrome |
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