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POS0737 (2021)
LOW PRECONCEPTIONAL COMPLEMENT LEVEL IS RELATED WITH ADVERSE OBSTETRIC OUTCOME IN A MULTICENTRIC COHORT OF PREGNANCY IN PATIENTS WITH APS ANDAPL POSITIVITY
D. Lini1, C. Nalli1, L. Andreoli1, F. Crisafulli1, M. Fredi1, M. G. Lazzaroni1, V. Bitsadze2, A. Calligaro3, V. Canti4, R. Caporali5, F. Carubbi6, C. Chighizola7, P. Conigliaro8, F. Conti9, C. De Carolis10, T. Del Ross11, M. Favaro11, M. Gerosa12, A. Iuliano13, J. Khizroeva2, A. Makatsariya2, P. L. Meroni12, M. Mosca14, P. Melissa15, R. Perricone8, P. Rovere-Querini16, G. D. Sebastiani13, C. Tani12, M. Tonello11, S. Truglia9, D. Zucchi12, F. Franceschini1, A. Tincani1
1University and ASST Spedali Civili of Brescia, Rheumatology Unit, Brescia, Italy
2I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Department of Obstetrics and Gynecology, Moscow, Russian Federation
3University Hospital of Padua, Padua, Rheumatology Unit, Department of Medicine, Padua, Italy
4RCCS San Raffaele Hospital, Immunology, Rheumatology, Allergology and Rare Disease - Laboratory of Autoimmunity and Vascular Inflammation, Milan, Italy
5ASST Gaetano Pini-Cto Institute, Division of Clinical Rheumatology - Department of Clinical Sciences and Community Health, Research Center for Adult and Pediatric Rheumatic Diseases, Milan, Italy
6School of Medicine, University of L’aquila, Department of Biotechnological and Applied Clinical Science, Rheumatology Unit, L’aquila, Italy
7Istituto Auxologico Italiano, University of Milan, Department of Clinical Sciences and Community Health -; Experimental Laboratory of Immunorheumatological Researches, Milan, Italy
8University of Rome Tor Vergata, Rheumatology, Allergology and Clinical Immunology, Department of “Medicina Dei Sistemi”, Rome, Italy
9Sapienza University of Rome, Reumatologia, Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche E Cardiovascolari, Rome, Italy
10Polymedical Center for Prevention of Recurrent Spontaneous Abortion, Polymedical Center for Prevention of Recurrent Spontaneous Abortion, Rome, Italy
11University Hospital of Padua, Rheumatology Unit, Department of Medicine, Padua, Italy
12Ospedale Gaetano Pini, University of Milan, Division of Rheumatology, Department of Clinical Sciences and Community Health, Milan, Italy
13Azienda Ospedaliera San Camillo-Forlanini, Rheumatology Unit, Roma, Italy
14University of Pisa, Rheumatology Unit, Department of Clinical and Experimental Medicine, Pisa, Italy
15University Of Ferrara, Division of Rheumatology, Department of Clinical Sciences, Ferrara, Italy
16IRCCS San Raffaele Hospital - San Raffaele University, Unit of Immunology, Rheumatology, Allergy and Rare Diseases, Milan, Italy

Background: The role of complement in the antiphospholipid (aPL) related pathology has been widely studied in animal models. Antiphospholipid antibodies can induce fetal loss in experimental animals but mice deficient in specific complement components (C4, C3, C5) appear somehow protected. In addition, in pregnant mice injected with aPL, antibody deposition has been found at decidual level causing focal necrosis, apoptosis and neutrophil infiltrates and supporting aPL pathogenetic potential. On the other hand, human studies did find hypocomplementemia associated to pregnancy complications in patients with obstetric antiphospholipid syndrome (APS). These results, however, are not unanimously confirmed and, in addition, some studies only show increased levels of complement activation products (i.e. Bb) and not decreased levels of C3 and/or C4. A recently study focusing on complement level in early pregnancy and before pregnancy showed a significant correlation with pregnancy complications and loss in a large cohort of primary APS.


Objectives: To investigate if the simple detection of low C3 and/or C4 could be considered a risk factor for adverse pregnancy outcome in APS and aPL carriers pregnancies.


Methods: We performed a multicentric study including patients from 10 Italian and 1 Russian Centers. Data on pregnancies in women with primary APS (n=434) and asymptomatic carriers with persistently positive aPL but not fulfilling clinical criteria for APS (n=218) were retrospectively collected. Serum C3 and C4 levels were evaluated by nephelometry; hypocomplementemia was defined by local laboratory reference values. Statistical analysis was performed using GraphPad.


Results: Preconceptional complement levels and gestational outcome were available for 107 (25%) pregnancies in APS out of 434 and for 196 (90%) pregnancies in aPL carriers women out of 218. In pregnancies with low preconceptional C3 and/or C4, a significantly higher prevalence of pregnancy losses was observed (p=0.019). A subgroup analysis focusing on triple aPL positive patients was also performed. Preconceptional low C3 and/or C4 levels were found to be associated with an increased rate of pregnancy loss (p = 0.027) in this subgroup also. Otherwise, adverse pregnancy outcomes in single or double aPL positive women were not related to preconception complement levels (p = 0.44) ( Table 1 ). Of note, all the pregnancy losses in the triple positive group occurred in patients treated with low dose aspirin and low molecular weight heparin from the time of positive pregnancy test.


Conclusion: Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of adverse outcome. This has been seen only in in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss. test positivity.


REFERENCES:

[1]De Carolis S, et al. Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome. Lupus (2012) 21:776–8.

[2]Kim MY, et al. Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. Ann Rheum Dis (2018) 77:549–55.

[3]Fredi M, et al. Risk Factors for Adverse Maternal and Fetal Outcomes in Women With Confirmed aPL Positivity: Results From a Multicenter Study of 283 Pregnancies. Front Immunol. 2018 May 7;9:864.

Triple aPL positivity Single or double aPL positivity
Gestational outcome Low C3/C4 (n=49 ) Normal C3/C4 (n=17 ) p Low C3/C4 (n=57 ) Normal C3/C4 (n=165 ) p
Term live birth (>37w ) 15 (31%) 6 (35%) ns 34 (60%) 110 (67%) ns
Preterm live birth (≤37w ) 22 (45%) 11 (65%) ns 15 (26%) 38 (23%) ns
Pregnancy losses (abortion and miscarriages ) 12 (24%) 0 (0%) 0.027 8 (14%) 17 (10%) ns

Disclosure of Interests: None declared


Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 619
Session: SLE, Sjögren’s and APS - clinical aspects (other than treatment) (POSTERS only)