THE ROLE OF PENTRAXIN-3 AS PREDICTOR OF PREGNANCY COMPLICATIONS IN PATIENTS WITH SLE AND/OR ANTI-PHOSPHOLIPID SYNDROME AND APL CARRIERS

Systemic Lupus Erythematosus (SLE) is an autoimmune disease affecting childbearing women. Nowadays, mainly due to preconception counselling, the overall prognosis of such pregnancies has consistently improved. Preconception visit is pivotal to assess anti-phospholipid (aPL) antibodies and/or anti-phospholipid syndrome (APS), drugs’ safety and disease activity, in order to prevent adverse pregnancy outcomes (APOs) and maternal flares. The general aim of the thesis was to improve the management of pregnant SLE and/or APS patients by assessing pregnancy outcomes and identifying predictors of APOs and flares. Firstly, we focused on severe preeclampsia (PE) leading to preterm delivery<34 weeks, which is one of the classification criteria of APS. The sample included 40 APS patients with severe PE enrolled in 6 European centres. PE occurred very early in gestation (median 25.5 weeks) and with a high mortality during the offspring (65%). In the follow-up period (5 years), none of these patients experienced 3 consecutive miscarriages, whereas thromboses, intrauterine foetal deaths and HELLP syndromes were observed, suggesting that recurrent miscarriages APS criterion may have a different physiopathology compared to the other criteria. Secondly, we tested a new score, the SLE-disease activity score (SLE-DAS) as predictor of flares and APOs in 2nd and 3rd trimester in SLE women enrolled at two referral centres (Italy and France). SLE activity was assessed at first trimester by SLE-pregnancy disease activity index (SLEPDAI) and SLE-DAS. In this cohort of 158 pregnant patients with a very stable lupus, a significant correlation between SLE-DAS and SLEPDAI was observed (Spearman’s ρ=0.97). Both SLE-DAS and SLEPDAI predicted flares (p=0.02 and p=0.01, respectively), and resulted associated with APOs (p=0.02). Thus, SLE-DAS seems a reliable instrument to measure SLE activity during pregnancy. Planning pregnancy when SLE is quiescent is a cornerstone of the management of SLE patients. However, the impact of lupus low disease activity state (LLDAS), remission and damage accrual in early gestation has never been simultaneously studied. We evaluated SLE women in the prospective GR2 study with an ongoing singleton pregnancy at 12 weeks (one pregnancy/woman). Several sets of criteria were used to define remission, disease activity, and damage. First trimester maternal and SLE features were tested as predictors of flares and APOs. 238 women (98.3% on hydroxychloroquine) had 230 live births. Thirty-five (14.7%) patients had at least one flare; APOs occurred in 34 (14.3%) women. At logistic regression models, damage (SLICC-Damage Index) (odds ratio-OR- 1.8, 95% confidence intervals-CI-: 1.1-2.9 for model 1 and OR 1.7, 95% CI: 1.1-2.8 for model 2) and lupus anticoagulant (LAC, OR 4.2, 95% CI: 1.8-9.7 for model 1; OR 3.7, 95% CI: 1.6-8.7 for model 2) resulted significantly associated with APOs. Hence, damage should be considered in preconception counselling and early gestation along with LAC. Pentraxin-3 (PTX3) has been studied as promising biomarker of pregnancy complications, although no data on SLE/APS pregnant women are available. Hence, we evaluated serum PTX-3 and anti-PTX3 antibodies as predictors of pregnancy outcomes in SLE and/or APS women at our Rheumatology Unit. The current analysis included pregnant SLE (SLICC 2012) and/or APS (Sydney, 2006) women. The control group included healthy patients/affected with other rheumatic diseases (nor SLE nor APS) referred to our clinic with a conception date <1st April 2021 (one pregnancy/patient). Among 79 pregnancies, APS occurred in 7 (8.9%), SLE in 9 (11.4%) and SLE with APS in 3 women (3,8%). Overall, the control group included 66 (83.6%) patients. Serum IgG anti-PTX3 Abs were found in 11 (13.9%, 95% CI 7.2-23.5) women. Anti-PTX3 were slightly associated with gestational diabetes mellitus (GDM) (p=0.04) and resulted slightly associated with intra-uterine growth restriction (p=0.09).