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 B.
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
C2 - 23983008
AN - SCOPUS:84889014593
SN - 0004-3591
VL - 65
SP - 3186
EP - 3193
JO - Arthritis and Rheumatism
JF - Arthritis and Rheumatism
IS - 12
ER -