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Abstract Number: 1966

Antibodies Against Domain 1 and Domain 4/5 of β2 Glycoprotein I: Clinical Relevance in Obstetric Anti-Phospholipid Syndrome

Cecilia B. Chighizola1, Laura Andreoli2,3, Marta Tonello4, Maria Gabriella Raimondo5, Francesca Pregnolato6, Cecilia Nalli7, Elena Mattia8, Laura Cesana9, Rajesh Kumar7, Chiara Comerio10, Claudia Grossi9, Francesco Mombelli11, Maria Gerosa12, Maria Orietta Borghi13, Amelia Ruffatti14, Angela Tincani15 and Pier Luigi Meroni16, 1Department of Clinical Sciences and Community Health, University of Milan, IRCCS Istituto Auxologico Italiano, Milano, Italy, 2Rheumatology & Clinical Immunology, University of Brescia/Spedali Civili, Brescia, Italy, 3University of Brescia, Spedali Civili, Brescia, Italy, 4Rheumatology Unit, Department of Medicine DIMED, University of Padua, Padova, Italy, 5University of Milan, Istituto Ortopedico Gaetano Pini, Milan, Italy, 6IRCCS Istituto Auxologico Italiano, Milano, Italy, 7Spedali Civili, Brescia, Italy, 8Azienda Ospedaliera of Padova, Padua, Italy, 9IRCCS Istituto Auxologico Italiano, Milan, Italy, 10University of Milan, Milan, Italy, 11University of Brescia, Brescia, Italy, 12University of Milan, Istituto Ortopedico Gaetano Pini, Milano, Italy, 13University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy, 14Azienda Ospedaliera of Padova, University of Padova, Padova, Italy, 15Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia, Italy, 16Rheumatology Department, University of Milan, Istituto Ortopedico Gaetano Pini, Milano, Italy

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: antiphospholipid antibodies and antiphospholipid syndrome

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Session Information

Date: Monday, November 14, 2016

Session Title: Antiphospholipid Syndrome

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: The domain reactivity of antibodies against b2 glycoprotein I (anti-b2GPI) has been investigated in patients with thrombotic anti-phospholipid syndrome (APS), leading to the identification of antibodies targeting domain 1 of the molecule (anti-D1) as the most relevant autoantibody subpopulation. Scarce attention has been paid to the domain profiling of patients with pregnancy morbidity (PM). The aim of this study was to characterize the relevance of the fine epitope reactivity of anti-b2GPI antibodies in anti-phospholipid antibody (aPL)-associated PM.

Methods: Women with persistent positivity for anti-b2GPI IgG antibodies at medium-high titers, with at least one pregnancy and without systemic autoimmune disease were included. Anti-D1 and anti-D4/5 antibodies were tested using a chemiluminescent immunoassay and a research ELISA assay, respectively (QUANTA Flash b2GPI IgG and QUANTA Lite, Inova Diagnostics).  Statistical analysis was performed using R package.

Results: 138 women fulfilling the inclusion criteria were retrospectively recruited at 3 referral centres. 49 patients (35%) had obstetric APS, 18 (13%) thrombotic APS, 37 (27%) thrombotic and obstetric APS while 34 women (25%) were asymptomatic aPL carriers. 81 women (60%) displayed triple aPL positivity, 32 (23%) had two positive aPL test and 23 (17%) carried a single aPL positivity. 110 patients had at least one untreated pregnancy, culminating in a live birth in 31 cases (28%). 89 women underwent a pregnancy course while receiving treatment, with 71 women (80%) having a live birth. A significant difference in the distribution of positive anti-D1 antibodies emerged between women with or without PM and with or without thrombosis (p=0.05, c2=2.710 and p<0.001, c2=12.174, respectively); no significant difference was observed for anti-D4/5 antibodies (Table 1). In a multivariate logistic regression model also encompassing treatment, positive anti-D1 antibodies, but not anti-D4/5, were significantly associated with obstetric complications, conferring an odds ratio (OR) of 2.32 (p=0.040 and p=0.724, respectively). Triple aPL positivity corrected by treatment significantly predicted PM (p=0.015, OR=2.78).

Conclusion: Our data suggest that anti-D1 antibodies are significantly associated not only with thrombosis but also with obstetric morbidity while positive anti-D4/5 antibodies are not predictive of PM.     Table 1. Different combinations of reactivity against D1 and D4/5 in women with or without pregnancy morbidity (PM) according to the updated classification Criteria for APS and in women with or without thrombosis.    

 

No PM (%)

PM (%)

No thrombosis (%)

Thrombosis (%)

Anti-D1+/anti-D4/5-

15 (29%)

43 (50%)

27 (33%)

31 (56%)

Anti-D1-/anti-D4/5+

9 (17%)

9 (11%)

16 (19%)

2 (4%)

Anti-D1+/anti-D4/5+

11 (21%)

14 (16%)

15 (18%)

13 (24%)

Anti-D1-/anti-D4/5-

17 (33%)

20 (23%)

25 (30%)

9 (16%)

Total

52

86

83

55

 


Disclosure: C. B. Chighizola, None; L. Andreoli, None; M. Tonello, None; M. G. Raimondo, None; F. Pregnolato, None; C. Nalli, None; E. Mattia, None; L. Cesana, None; R. Kumar, None; C. Comerio, None; C. Grossi, None; F. Mombelli, None; M. Gerosa, None; M. O. Borghi, None; A. Ruffatti, None; A. Tincani, None; P. L. Meroni, None.

To cite this abstract in AMA style:

Chighizola CB, Andreoli L, Tonello M, Raimondo MG, Pregnolato F, Nalli C, Mattia E, Cesana L, Kumar R, Comerio C, Grossi C, Mombelli F, Gerosa M, Borghi MO, Ruffatti A, Tincani A, Meroni PL. Antibodies Against Domain 1 and Domain 4/5 of β2 Glycoprotein I: Clinical Relevance in Obstetric Anti-Phospholipid Syndrome [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/antibodies-against-domain-1-and-domain-45-of-%ce%b22-glycoprotein-i-clinical-relevance-in-obstetric-anti-phospholipid-syndrome/. Accessed January 24, 2021.
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