Correlation between Antibodies to the Phosphotidylserine/Prothrombin Complex (aPS/PT) and Anti-β2glycoprotein-1-Domain 1 (anti-β2GP1-D1) and Vascular Thrombosis (VT) and/or Pregnancy Morbidity (PM)

Eric Campbell¹, Tania Pannu¹, Marvin J. Fritzler², Michelle Jung³, Claire Barber⁴, Yvan St. Pierre⁵ and Ann E. Clarke², ¹Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, ²Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, ³Division of Rheumatology, University of Calgary, Calgary, AB, Canada, ⁴Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, ⁵Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Antiphospholipid antibodies, SLE and thrombosis

Session Information

Date: Tuesday, October 23, 2018

Title: Reproductive Issues in Rheumatic Disorders Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: aPS/PT is considered to be a risk factor for vascular thrombosis (VT) and/or pregnancy morbidity (PM). Anti-β2GP1-D1 is potentially superior to anti-β2GP1 in predicting VT/PM. We examined the correlation between aPS/PT and anti-β2GP1-D1 and the laboratory criteria for antiphospholipid antibody syndrome (APS): lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-β2GP1 and their association with VT/PM.

Methods: Multiple serum samples from patients fulfilling the ACR or Systemic Lupus International Collaborating Clinics (SLICC) Criteria for SLE were analyzed for aPS/PT (IgG/IgM) by ELISA (QUANTA Lite, Inova Diagnostics), anti-β2GP1-D1 by chemiluminescence immunoassay (QUANTA Flash, Inova), LAC using tissue thromboplastin inhibition test and dRVVT, and aCL (IgG) and anti-β2GP1 (IgG) by ELISA. VT/PM was based on patient self-report and confirmed by chart review. VT included arterial, venous, or small vessel thrombosis; PM included ≥ one fetal death >10 weeks, ≥ one premature birth <34 weeks or >3 spontaneous abortions <10 weeks.

The Spearman correlation between aPS/PT and anti-β2GP1-D1 and the conventional AP autoantibodies and between each autoantibody and VT/PM was calculated. The association between number of autoantibodies and VT/PM was assessed using univariate logistic regression.

Results: 199 patients were included, of which 64 had had VT/PM (Table 1). The percentage of patients ever positive for aPS/PT, anti-β2GP1-D1, LAC, aCL, and anti-β2GP1 was significantly higher among those with VT/PM (Table 1). The correlation (95% CI) between IgG aPS/PT and LAC, aCL, anti-β2GP1, and anti-β2GP1-D1 was 0.54 (0.43, 0.64), 0.40 (0.27, 0.51), 0.43 (0.30, 0.54) and 0.28 (0.14, 0.42), respectively (Table 2). The correlation between IgM aPS/PT and LAC, aCL, anti-β2GP1 and anti-β2GP1-D1 was 0.43 (0.31, 0.54), 0.16 (0.02, 0.30), 0.25 (0.11, 0.38) and 0.24 (0.09, 0.38). The correlation between anti-β2GP1-D1 and LAC, aCL and anti-β2GP1 was 0.28 (0.13, 0.42), 0.55 (0.43, 0.64) and 0.61 (0.50, 0.69). The correlation between IgG aPS/PT, IgM aPS/PT, anti-β2GP1-D1, LAC, aCL, and anti-β2GP1 and VT/PM was 0.17 (0.03, 0.30), 0.05 (-0.09, 0.19), 0.21 (0.06, 0.35), 0.22 (0.08, 0.35), 0.22 (0.08, 0.35) and 0.24 (0.10, 0.37), respectively. The odds (95% CI) of VT/PM increased incrementally by 46% for each additional autoantibody (1.15, 1.86).

Table 1: Demographics and Clinical Characteristics of Cohort at last Follow-up (n = 199)
	VT/PM +ve (n=64)	VT/PM –ve (n=135)
Age, mean, yrs	51.6	47.5
Disease duration, mean, yrs	16.4	13.2
Female, %	89.1	94.1
Ethnicity, % Caucasian	68.9	55.7
SLEDAI-2K	3.9	3.3
SDI	2.7*	1.0*
Medications, % currently using
Antimalarials	81.5	83.5
Steroids	41.5	26.2
Immunosuppressants	37.0	33.0
Biologics	1.9	0
Anticoagulants, % ever on	72.4* (for VT only)	5.9*
Autoantibodies, ever +ve %
ANA, %	90.9	85.4
Anti-dsDNA, %	54.3	40.9
SSA/Ro60	37.8	35.9
SSB/La	13.3	16.3
Sm	28.9	15.2
U1-RNP	28.9	25.0
LAC	24.6*	8.3*
aCL	21.9*	6.8*
anti-ß2GP1	23.4*	6.9*
aPS/PT (IgG)	26.7*	13.0*
aPS/PT (IgM)	33.3	28.2
anti-D1-ß2GP1	13.2*	2.6*
≥ 1 Vascular thrombosis, %	90.6	–
≥ 1 Pregnancy morbidity, %	12.5	–

*= significant differences at 95% CI

Table 2: Correlation between aPS/PT and anti-D1- β2GP1 and antiphospholipid antibodies (95% CI)
	aPS/PT (IgG) +ve	aPS/PT (IgM) +ve	anti-D1-β2GP1 +ve
LAC	0.54 (0.43, 0.64	0.43 (0.31, 0.54)	0.28 (0.13, 0.42)
aCL	0.40 (0.27, 0.51)	0.16 (0.02, 0.30)	0.55 (0.43, 0.64)
anti-β2GP1	0.43 (0.30, 0.54)	0.25 (0.11, 0.38)	0.61 (0.50, 0.69)
anti-D1-β2GP1	0.28 (0.14, 0.42)	0.24 (0.09, 0.38)	–

Conclusion: IgG aPS/PT and anti-β2GP1-D1 are highly correlated with other AP antibodies, which along with the accepted criteria of APS, are all similarly correlated with VT/PM. IgG aPS/PT and anti-β2GP1-D1 should be considered as criteria for APS.

Disclosure: E. Campbell, None; T. Pannu, None; M. J. Fritzler, Inova Diagnostics Inc., BioRad, Euroimmun GmbH, Mikrogen GmbH, Dr. Fooke Laboratorien GmbH, ImmunoConcepts, SKF Canada, Amgen and Pfizer, 5,ImmunoConcepts, Inova Diagnostics, Euroimmun GmbH, and Alexion Canada, 7; M. Jung, None; C. Barber, None; Y. St. Pierre, None; A. E. Clarke, Bristol-Myers Squibb, 5,AstraZeneca, 5,Exagen Diagnostics, 5,AstraZeneca, 9,Celgene Corporation, 9.

To cite this abstract in AMA style:

Campbell E, Pannu T, Fritzler MJ, Jung M, Barber C, St. Pierre Y, Clarke AE. Correlation between Antibodies to the Phosphotidylserine/Prothrombin Complex (aPS/PT) and Anti-β2glycoprotein-1-Domain 1 (anti-β2GP1-D1) and Vascular Thrombosis (VT) and/or Pregnancy Morbidity (PM) [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/correlation-between-antibodies-to-the-phosphotidylserine-prothrombin-complex-aps-pt-and-anti-%ce%b22glycoprotein-1-domain-1-anti-%ce%b22gp1-d1-and-vascular-thrombosis-vt-and-or-pregnancy-morbidi/. Accessed .

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