Anti-â2GP1- Domain-1 Antibodies Are a Marker Of APS Severity

Nancy Agmon-Levin¹, Luciana Seguro², Cristina Rosário³, Michael Mahler⁴, Mariele Gatto⁵, Nir Tomer⁶, Elaine P. Leon⁷, Andrea Doria⁸, László Kovács⁹, Nathalie Costedoat-Chalumeau¹⁰, Boris Gilburd¹¹ and Yehuda Shoenfeld¹², ¹The Zabludowicz Center for Autoimmune Diseases, Tel-Hashomer, Israel, ²Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, ³Internal Medicine Department, Hospital de Pedro Hispano, Rua Dr. Eduardo Torres Matosinhos, Porto, Portugal, ⁴Research, INOVA Diagnostics, San Diego, CA, ⁵Department of Medicine-DIMED, University of Padova, Padova, Italy, ⁶The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel, ⁷Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, ⁸Division of Rheumatology, University of Padova, Padova, Italy, ⁹Department of Rheumatology, University of Szeged, Szeged, Hungary, ¹⁰Internal Medicine, Hopital Cochin, Paris, France, ¹¹The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel, ¹²The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Ramat Gan, Israel

Meeting: ACR/ARHP Annual Meeting 2013

Keywords: APL and antibodies

Session Information

Title: Antiphospholipid Syndrome: Clinical Manifestations and New Biomarkers in Antiphospholipid Syndrome

Session Type: Abstract Submissions (ACR)

Background/Purpose: Autoantibodies targeting Domain-1(D1) of beta-2-glycoprotein-1(β2GP1) are common among patients with the antiphospholipid syndrome (APS)¹. However, few studies assessed their clinical relevance and correlation with other anti-phospholipid antibodies (aPLA). Thus, in the current study we evaluated the correlations between anti-β2GP1-D1 levels and APS clinical and serological parameters.

Methods: Serum samples of 178 APS patients, 50 healthy subjects and 47 patients diagnosed with sepsis were utilized to determine levels of IgG-antibodies to cardiolipin(aCL), β2GP1 and β2GP1-D1 (BIO-FLASH®, INOVA). Demographic, clinical and serological (i.e. Lupus anticoagulant (LAC)) data were analyzed.

Results: Among APS patients aCL, anti-β2GP1 and anti-β2GP1-D1 were present in 60%, 70% and 49%, respectively. The presence of anti-β2GP1-D1 antibodies correlated with the presence of LAC (91 vs. 67%; p<0.001), aCL (98 vs. 23%; p<0.001). Triple aPLA positivity was present in 89% of anti-β2GP1-D1 positive sample compared with 16% among anti-β2GP1-D1 negative samples (p<0.001). Anti-β2GP1-D1 antibodies correlated with higher titers of aCL antibodies (p<0.001) and anti -β2GP1 (p=0.03).

Anti β2GP1 antibodies correlated with the occurrence of venous thrombosis (p< 0.009). Anti-β2GP1-D1 positivity (>20CU) related to the occurrence of any thrombotic event (91% vs. 79% OR 2.54; 95% CI 1.05-6.15; p=0.039). Medium levels of anti-β2GP1-D1 (>30CU) correlated with arterial thrombosis (55% vs. 33% OR=2.5; 95%CI 1.37-4.67; p = 0.006). High levels of anti-β2GP1-D1 (>64CU) were associated with multiple thrombotic events (62% vs. 31% OR 3.58; 95%CI 1.49-8.61; p=0.005) arterial thrombosis (60% vs. 33% OR 3.04; 95%CI 1.61-5.73; p=0.001) and CNS manifestations (45% vs. 27% OR 1.99; 95%CI 1.03-3.81; p=0.038).

Conclusion: In our cohort of APS patients, anti-β2GP1-D1 antibodies were a marker of high risk aPLA profile. Moreover their presence, particularly in med-high levels correlated with repeated thromboses, arterial occlusion and CNS-related manifestations. Thus, anti-β2GP1-D1 may potentially serve as a biomarker of thrombosis in APS.

¹ Mahler M, et al Autoimmun Rev. 2012;12(2):313-7.

Disclosure:

N. Agmon-Levin,
None;

L. Seguro,
None;

C. Rosário,
None;

M. Mahler,

Inova Diagnostics, Inc.,

M. Gatto,
None;

N. Tomer,
None;

E. P. Leon,
None;

A. Doria,
None;

L. Kovács,
None;

N. Costedoat-Chalumeau,
None;

B. Gilburd,
None;

Y. Shoenfeld,
None.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-a2gp1-domain-1-antibodies-are-a-marker-of-aps-severity/