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Published on: September 9, 2012
Factor H Autoantibodies in Patients with Antiphospholipid Syndrome and Thrombosis
Anna Foltyn Zadura1, Ashfaque A Memon1, Ljudmila Stojanovich1
1From the Department of Translational Medicine, and Department of Clinical Sciences, Lund University; Center for Primary Health Care Research, Skåne University Hospital, Malmö; Department of Clinical Chemistry and Transfusion Medicine, Halland Hospital, Halmstad, Sweden; Internal Medicine, "Bezhanijska Kosa," University Medical Center, Belgrade, Serbia; Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Aviv, Israel; Telethon Kids Institute, University of Western Australia, Perth, Australia; Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.A. Foltyn Zadura, MSc, Department of Translational Medicine, Lund University; A.A. Memon, PhD, Center for Primary Health Care Research, Skåne University Hospital; L. Stojanovich, MD, PhD, Internal Medicine, "Bezhanijska Kosa," University Medical Center; C. Perricone, MD; F. Conti, MD, PhD; G. Valesini, MD, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma; G. Bogdanovic, MD, PHD, Internal Medicine, "Bezhanijska Kosa," University Medical Center; A. Hillarp, PhD, Department of Clinical Chemistry and Transfusion Medicine, Halland Hospital; Y. Shoenfeld, MD, PhD, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center; J. Sundquist, MD, PhD, Center for Primary Health Care Research, Skåne University Hospital; J. Leffler, PhD, Telethon Kids Institute, University of Western Australia; P.J. Svensson, MD, PhD, Department of Translational Medicine, Lund University; L.A. Trouw, PhD, Department of Rheumatology, Leiden University Medical Center; A.M. Blom, PhD, Department of Translational Medicine, Lund University.
Objective:
Autoantibodies to complement factor H (FH) are associated with atypical hemolytic uremic syndrome, but can also be detected in patients with rheumatoid arthritis and in patients positive for lupus anticoagulants and thus potentially antiphospholipid syndrome (APS). To our knowledge, no data are available on the association between the presence of FH autoantibodies in APS and clinical manifestations.
Methods:
We determined FH autoantibody levels using ELISA in 2 cohorts of patients with primary (PAPS) and secondary APS (SAPS) from Serbia and Italy, and an additional cohort including patients with venous thromboembolism (VTE) from Sweden.
Results:
FH autoantibodies were detected in 13.7% of patients (n = 73) with PAPS and 30.3% of patients (n = 33) with SAPS in the Serbian cohort. FH autoantibody frequency in the Italian cohort was 33.3% (n = 15) and 36% (n = 25) in PAPS and SAPS, respectively. Both FH autoantibody levels and frequencies observed in both APS cohorts were significantly higher than in matched healthy controls (5%). Further, patients with PAPS with venous thrombosis in the Serbian cohort had significantly higher levels of FH autoantibodies. Therefore, we analyzed a dedicated Swedish thrombosis cohort and found that patients with FH autoantibody positivity had higher risk of VTE recurrence (HR 2.0, 95% CI 1.2-3.3, p = 0.011) compared with the reference group of FH autoantibody-negative patients.
Conclusion:
Overall, the data indicate that in patients with APS and recurrent venous thrombosis, there are increased levels of FH autoantibodies, a finding associated with poor clinical outcome.
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