Value of isolated IgA anti-β2-glycoprotein i positivity in the diagnosis of the antiphospholipid syndrome

Vijaya Murthy, Rohan Willis, Zurina Romay-Penabad, Patricia Ruiz-Limõn, Laura A. Martínez-Martínez, Shraddha Jatwani, Praveen Jajoria, Alan Seif, Graciela S. Alarcõn, Elizabeth Papalardo, Jigna Liu, Luis M. Vilá, Gerald McGwin, Terry A. McNearney, Rashmi Maganti, Prashanth Sunkureddi, Trisha Parekh, Michael Tarantino, Ehtisham Akhter, Hong Fang & 8 others Emilio Gonzalez, Walter R. Binder, Gary L. Norman, Zakera Shums, Marius Teodorescu, John D. Reveille, Michelle Petri, Silvia S. Pierangeli

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Objective: To examine the prevalence of isolated IgA anti- β2-glycoprotein I (anti-β2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-β2GPI 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-β2GPI titers and binding to domain IV/V of β2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-β2GPI 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-β2GPI isotype, and 57 patients were positive exclusively for IgA anti-β2GPI 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- β2GPI-positive serum samples reacted with domain IV/V of anti-β2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-β2GPI 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-β2GPI 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-β2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. Conclusion: Isolated IgA anti-β2GPI-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-β2GPI antibodies directed to domain IV/V of β2GPI represent an important subgroup of clinically relevant antiphospholipids.

Original languageEnglish (US)
Pages (from-to)3186-3193
Number of pages8
JournalArthritis and Rheumatism
Volume65
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

Antiphospholipid Syndrome
Glycoproteins
Thrombosis
Antibodies
Thromboplastin
Systemic Lupus Erythematosus
anti-IgA
Enzyme-Linked Immunosorbent Assay
Serum
Venous Thrombosis
Virulence

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Murthy, V., Willis, R., Romay-Penabad, Z., Ruiz-Limõn, P., Martínez-Martínez, L. A., Jatwani, S., ... Pierangeli, S. S. (2013). Value of isolated IgA anti-β2-glycoprotein i positivity in the diagnosis of the antiphospholipid syndrome. Arthritis and Rheumatism, 65(12), 3186-3193. https://doi.org/10.1002/art.38131

Value of isolated IgA anti-β2-glycoprotein i positivity in the diagnosis of the antiphospholipid syndrome. / Murthy, Vijaya; Willis, Rohan; Romay-Penabad, Zurina; Ruiz-Limõn, Patricia; Martínez-Martínez, Laura A.; Jatwani, Shraddha; Jajoria, Praveen; Seif, Alan; Alarcõn, Graciela S.; Papalardo, Elizabeth; Liu, Jigna; Vilá, Luis M.; McGwin, Gerald; McNearney, Terry A.; Maganti, Rashmi; Sunkureddi, Prashanth; Parekh, Trisha; Tarantino, Michael; Akhter, Ehtisham; Fang, Hong; Gonzalez, Emilio; Binder, Walter R.; Norman, Gary L.; Shums, Zakera; Teodorescu, Marius; Reveille, John D.; Petri, Michelle; Pierangeli, Silvia S.

In: Arthritis and Rheumatism, Vol. 65, No. 12, 12.2013, p. 3186-3193.

Research output: Contribution to journalArticle

Murthy, V, Willis, R, Romay-Penabad, Z, Ruiz-Limõn, P, Martínez-Martínez, LA, Jatwani, S, Jajoria, P, Seif, A, Alarcõn, GS, Papalardo, E, Liu, J, Vilá, LM, McGwin, G, McNearney, TA, Maganti, R, Sunkureddi, P, Parekh, T, Tarantino, M, Akhter, E, Fang, H, Gonzalez, E, Binder, WR, Norman, GL, Shums, Z, Teodorescu, M, Reveille, JD, Petri, M & Pierangeli, SS 2013, 'Value of isolated IgA anti-β2-glycoprotein i positivity in the diagnosis of the antiphospholipid syndrome', Arthritis and Rheumatism, vol. 65, no. 12, pp. 3186-3193. https://doi.org/10.1002/art.38131
Murthy V, Willis R, Romay-Penabad Z, Ruiz-Limõn P, Martínez-Martínez LA, Jatwani S et al. Value of isolated IgA anti-β2-glycoprotein i positivity in the diagnosis of the antiphospholipid syndrome. Arthritis and Rheumatism. 2013 Dec;65(12):3186-3193. https://doi.org/10.1002/art.38131
Murthy, Vijaya ; Willis, Rohan ; Romay-Penabad, Zurina ; Ruiz-Limõn, Patricia ; Martínez-Martínez, Laura A. ; Jatwani, Shraddha ; Jajoria, Praveen ; Seif, Alan ; Alarcõn, Graciela S. ; Papalardo, Elizabeth ; Liu, Jigna ; Vilá, Luis M. ; McGwin, Gerald ; McNearney, Terry A. ; Maganti, Rashmi ; Sunkureddi, Prashanth ; Parekh, Trisha ; Tarantino, Michael ; Akhter, Ehtisham ; Fang, Hong ; Gonzalez, Emilio ; Binder, Walter R. ; Norman, Gary L. ; Shums, Zakera ; Teodorescu, Marius ; Reveille, John D. ; Petri, Michelle ; Pierangeli, Silvia S. / Value of isolated IgA anti-β2-glycoprotein i positivity in the diagnosis of the antiphospholipid syndrome. In: Arthritis and Rheumatism. 2013 ; Vol. 65, No. 12. pp. 3186-3193.
@article{a1aec3ccaf7e44fdb796606009d8246c,
title = "Value of isolated IgA anti-β2-glycoprotein i positivity in the diagnosis of the antiphospholipid syndrome",
abstract = "Objective: To examine the prevalence of isolated IgA anti- β2-glycoprotein I (anti-β2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-β2GPI 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-β2GPI titers and binding to domain IV/V of β2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-β2GPI 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-β2GPI isotype, and 57 patients were positive exclusively for IgA anti-β2GPI 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- β2GPI-positive serum samples reacted with domain IV/V of anti-β2GPI, and 77{\%} of those had clinical features of APS. Isolated IgA anti-β2GPI 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-β2GPI 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-β2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. Conclusion: Isolated IgA anti-β2GPI-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-β2GPI antibodies directed to domain IV/V of β2GPI represent an important subgroup of clinically relevant antiphospholipids.",
author = "Vijaya Murthy and Rohan Willis and Zurina Romay-Penabad and Patricia Ruiz-Lim{\~o}n and Mart{\'i}nez-Mart{\'i}nez, {Laura A.} and Shraddha Jatwani and Praveen Jajoria and Alan Seif and Alarc{\~o}n, {Graciela S.} and Elizabeth Papalardo and Jigna Liu and Vil{\'a}, {Luis M.} and Gerald McGwin and McNearney, {Terry A.} and Rashmi Maganti and Prashanth Sunkureddi and Trisha Parekh and Michael Tarantino and Ehtisham Akhter and Hong Fang and Emilio Gonzalez and Binder, {Walter R.} and Norman, {Gary L.} and Zakera Shums and Marius Teodorescu and Reveille, {John D.} and Michelle Petri and Pierangeli, {Silvia S.}",
year = "2013",
month = "12",
doi = "10.1002/art.38131",
language = "English (US)",
volume = "65",
pages = "3186--3193",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "12",

}

TY - JOUR

T1 - Value of isolated IgA anti-β2-glycoprotein i positivity in the diagnosis of the antiphospholipid syndrome

AU - Murthy, Vijaya

AU - Willis, Rohan

AU - Romay-Penabad, Zurina

AU - Ruiz-Limõn, Patricia

AU - Martínez-Martínez, Laura A.

AU - Jatwani, Shraddha

AU - Jajoria, Praveen

AU - Seif, Alan

AU - Alarcõn, Graciela S.

AU - Papalardo, Elizabeth

AU - Liu, Jigna

AU - Vilá, Luis M.

AU - McGwin, Gerald

AU - McNearney, Terry A.

AU - Maganti, Rashmi

AU - Sunkureddi, Prashanth

AU - Parekh, Trisha

AU - Tarantino, Michael

AU - Akhter, Ehtisham

AU - Fang, Hong

AU - Gonzalez, Emilio

AU - Binder, Walter R.

AU - Norman, Gary L.

AU - Shums, Zakera

AU - Teodorescu, Marius

AU - Reveille, John D.

AU - Petri, Michelle

AU - Pierangeli, Silvia S.

PY - 2013/12

Y1 - 2013/12

N2 - Objective: To examine the prevalence of isolated IgA anti- β2-glycoprotein I (anti-β2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-β2GPI 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-β2GPI titers and binding to domain IV/V of β2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-β2GPI 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-β2GPI isotype, and 57 patients were positive exclusively for IgA anti-β2GPI 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- β2GPI-positive serum samples reacted with domain IV/V of anti-β2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-β2GPI 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-β2GPI 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-β2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. Conclusion: Isolated IgA anti-β2GPI-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-β2GPI antibodies directed to domain IV/V of β2GPI represent an important subgroup of clinically relevant antiphospholipids.

AB - Objective: To examine the prevalence of isolated IgA anti- β2-glycoprotein I (anti-β2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-β2GPI 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-β2GPI titers and binding to domain IV/V of β2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-β2GPI 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-β2GPI isotype, and 57 patients were positive exclusively for IgA anti-β2GPI 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- β2GPI-positive serum samples reacted with domain IV/V of anti-β2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-β2GPI 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-β2GPI 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-β2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. Conclusion: Isolated IgA anti-β2GPI-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-β2GPI antibodies directed to domain IV/V of β2GPI represent an important subgroup of clinically relevant antiphospholipids.

UR - http://www.scopus.com/inward/record.url?scp=84889014593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84889014593&partnerID=8YFLogxK

U2 - 10.1002/art.38131

DO - 10.1002/art.38131

M3 - Article

VL - 65

SP - 3186

EP - 3193

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 12

ER -