Objectives To investigate fetal/perinatal and maternal outcomes from a large multicentre cohort of women diagnosed with UCTD. Methods This multicentre retrospective cohort study describes the outcomes of 224 pregnancies in 133 consecutive women with a diagnosis of UCTD, positive for ANA and aged <45 years old at study inclusion. Results Of the 224 pregnancies analysed, 177 (79%) resulted in live births, 45 (20.1%) in miscarriages (defined as pregnancy loss before 12 weeks’ gestation), 2 (0.9%) in stillbirths (pregnancy loss after 20 weeks’ gestation) and 6 (2.7%) cases showed intrauterine growth restriction. Miscarriages and stillbirths were strongly associated with the presence of aPL and ENA antibodies (P < 0.05). Maternal pregnancy complications were as follows: 5 (2.2%) cases developed pre-eclampsia, 11 (4.9%) cases gestational hypertension and 12 (5.4%) cases gestational diabetes. Joint involvement represented the most frequent clinical manifestation of the cohort (57.9%), followed by RP (40.6%), photosensitivity (32.3%) and haematological manifestations (27.1%). The rate of disease evolution of our cohort from a diagnosis of UCTD to a diagnosis of definite CTD was 12% within a mean time of 5.3 ± 2.8 years. With a total follow-up after first pregnancy of 1417 patient-years, we observed the evolution to a defined CTD in one out of every 88 patient- years. Conclusion In our multicentre cohort, women with UCTD had a live birth rate of 79%. Women with UCTD should be referred to specialist follow-up when planning a pregnancy. ENA profiling and aPL testing should be mandatory in this setting, and further therapeutic approaches and management should be planned accordingly.

Objective: Neonatal Lupus (NL) is a rare syndrome caused by placental transfer of maternal anti-SSA/Ro and anti-La/SSB autoantibodies to the fetus. The rarity of this condition requires the establishment of multidisciplinary registries in order to improve our knowledge. Method: Inclusion criteria in this retrospective study were the maternal confirmed positivity for anti-SSA/Ro and/or anti-SSB/La antibodies, and the presence of II or III degree congenital heart block (CHB) in utero or neonatal period (up to 27 days after birth). Result: Eighty-nine cases of CHB were observed in 85 women with 88 pregnancies that occurred between 1969 and 2017. CHB was mostly detected in utero (84 cases, 94.2%), while five cases were observed in the neonatal period. A permanent pacemaker was implanted in 51 of 73 children born alive (69.8), whereas global mortality rate was 25.8% (23 cases): 16 in utero , five perinatal, and two during childhood. By univariate analysis, factors associated with fetal death were pleural effusion ( p = 0.005, OR > 100; CI 95% 2.88->100 and hydrops ( p = 0.003, OR = 14.09; CI 95% 2.01–122). Fluorinated steroids (FS) were administered in 71.4% pregnancies, and its use was not associated with better survival. Some centers treated all cases with fluorinated steroids and some centers did not treat any case. CHB was initially incomplete in 24 fetuses, and of them five cases of II degree block reverted to a lower degree block after treatments. Recurrence rate in subsequent pregnancies was 17.6% (3 out of 17). A prophylactic treatment was introduced in 10 of these 16 subsequent (58.8%) pregnancies, mostly with FS or high dose intravenous immunoglobulins. Conclusion: This is the first report from the Italian Registry of neonatal lupus/CHB. The live birth rate was nearly 80%, with nearly two thirds of the children requiring the implantation of a pacemaker. The management of fetuses diagnosed with CHB was heterogeneous across Italian Centers. The registry at present is mainly rheumatological, but involvement of pediatric cardiologists and gynecologists is planned.

The clinical significance of antiphospholipid antibodies (aPL) in the context of infections has attracted attention since their first discovery in patients with syphilis. In fact, the recognition of aPL in patients with infections has been described in parallel to the understating of the syndrome. Since the first description of aPL-positive tests in three patients with COVID-19 diagnosed in January 2020 in Wuhan, China, a large number of studies took part in the ongoing debate on SARS-2-Cov 2 induced coagulopathy, and many following reports speculated a potential role for aPL. In order to get further insights on the effective role of detectable aPL in the pro-thrombotic status observed in COVID-19 patients, we performed an observational age-sex controlled study to compare the aPL profile of hospitalized patients with COVID with those observed in a) patients with thrombotic APS and b) patients with cultural/serologically-proved infections. Our data showed positive aPL testing in about half of the patients (53%) with COVID-19 and patients with other viral/bacterial infections (49%). However, aPL profile was different when comparing patients with overt APS and patients with aPL detected in the contest of infections. Caution is therefore required in the interpretation and generalization of the role of aPL s in the management of patients with COVID-19. Before introducing aPL testing as a part of the routine testing in patients with COVID-19, larger well-designed clinical studies are required. While the pro-thrombotic status in patients with COVID-19 is now unquestionable, different mechanisms other than aPL should be further investigated.

Basophil Activation Test: Methods Basophil Activation Test (BAT) was performed according to a previously reported technique [E1]. Briefly, endotoxin-free heparinized whole-blood samples were obtained from the allergic patients and a healthy control. Cells were challenged with 100 μl of anti-IgE (10 μg/ml; clone G7-18;BD Bioscience, USA), allergens (donkey raw milk diluted 1:50 in buffer; cow milk extract from prick test, Lofarma, Italy, undiluted), fMLP (0.5 μg/ml; Sigma Aldrich, Italy) for 20 min at 37 ° C in a water bath (optimal stimulation times were assessed in previous experiments). As a negative control, Tyrode solution (Sigma Aldrich) with 20 μ M HEPES and 7.5% NaHCO 3, pH 7.4, was used to assess the spontaneous expression of the different markers. The reactions were terminated by chilling the cells on ice. Immunophenotyping and Flow-Cytometric Analyses Basophils were stained with 5 μl of anti-human CD3 Pacific Blue (Beckman Coulter, USA), 10 μl of anti-human CD63-FITC (clone H5C6; BD Biosciences), 10 μl of anti-human CD203c-APC (clone NP4D6; BioLegend) and 10 μl of monoclonal anti-human CD294 (CRTH2) PE (Beckman Coulter, USA) for 15 min on room temperature. Flow-cytometric analyses were performed on a NAVIOS flow cytometer (Beckman Coulter, USA). We gated on physical parameters forward (FS) and side (SS) scatter to exclude debris. We then gated on CRTH2 (CD294) positive/CD3 negative cells to isolate basophils.

We aimed to investigate the impact of applying the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) in a previously described cohort of women with undifferentiated connective tissue disease (UCTD). MethodsThis study included 133 women with UCTD. At the time of inclusion into the study, none

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Background:Congenital heart block (CHB) is due to placental transfer of maternal anti-Ro/SSA autoantibodies to the fetus. The prevalence of CHB has been estimated as 1-2% in anti-Ro/SSA women while the recurrence rate is 16-19% (1). This condition is associated with a high rate of fetal/neonatal mortality and most of the cases requires pacemaker (PM) pacing. Given the rarity of CHB, limited data are available regarding the long-term follow-up of the offspring other than the cardiovascular complications.Objectives:The results of the Italian Registry of the autoimmune congenital heart block were recently described (2). A peculiarity of this cohort was that most of the mothers had an established diagnosis of systemic autoimmune disease at CHB detection, in contrast with other registries where CHB was mostly incidentally detected in healthy women. Here we report an update, with the preliminary data regarding the long-term outcome of patients with CHB, their unaffected siblings and health controls born from mothers positive for Ro/SSA.Methods:Data regarding demography, treatment, maternal, neonatal outcome, and follow-up were collected through an online electronic datasheet. A dedicated questionnaire was created with the aim to investigate general health, cardiovascular follow-up, and frequency of autoimmune diseases.Results:One-hundred and five cases of CHB in 99 patients were included from 1969 to December 2020. CHB was mostly detected in utero (97 cases, 92.3%) with 8 neonatal cases. Third degree CHB occurred in 71 cases (67.6%). Child mortality was observed in 29 (27.6%) cases: 20 in utero, 7 during neonatal period and 2 during childhood. Overall, a PM was implanted in 54 out of the 85 live births (63.5%). Then, our cohort was divided into 2 subgroups: pregnancy that occurred before (N=61) and after 2010 (N=44) with the aim to evaluate possible differences among the subgroups. Whereas mortality, PM, CHB degree were similar, CHB more frequently occurred in the last 10 years among Ro/SSA asymptomatic carriers than in the group of pregnancies before 2010 (53.6% vs 32.8%, p=0.038). Questionnaires from 14 surviving CHB cases, 8 unaffected siblings 12 controls born from mothers Ro/SSA positive were collected. Among CHB cases, 6 were males and 8 females, median age 12 years (range 6-28). All presented a third degree CHB, 10 required a neonatal PM pacing and one had an implantable ECG recorder. PM was substituted at least once in 9 patients, the oldest patient had to change it four times. No dilated cardiomyopathy occurred and most of the patients maintain an annual follow-up. Two cases of autoimmune diseases were registered among CHB cases, one idiopathic juvenile arthritis and one Cogan’s vasculitis, both born from mothers with Sjogren Syndrome. Four cases of neurodevelopmental disorders occurred: three cases of learning disabilities (one in each group) and one case of speech disorder in the sibling group. In addition, a CHB case presented a stress disorder linked to frequent hospitalizations.Conclusion:This registry is an ongoing project aiming at collecting all Italian CHB. Moreover, here we reported the preliminary data concerning the evaluation of long-term follow-up of CHB patients. Our data, even if need to be confirmed in larger cohort, seems reassuring: no differences were reported comparing CHB patients with unaffected siblings or controls.References:[1]Brito-Zéron et al. Nat Rev Rheumatol 2015;11:301-312.[2]Fredi M et al. Front Cardiovasc Med. 2019 Feb 28;6:11.Disclosure of Interests:None declared

Introduction: Asthma, along with inhaled steroids, was initially considered a risk factor for worse clinical outcomes in COVID-19. This was related to the higher morbidity observed in asthma patients during previous viral outbreaks. This retrospective study aimed at evaluating the prevalence of asthma among patients admitted due to SARS-CoV-2 infection as well as the impact of inhaled therapies on their outcomes. Furthermore, a comparison between patients with asthma, COPD and the general population was made. Methods: All COVID-19 inpatients were recruited between February and July 2020 from four large hospitals in Northwest Italy. Data concerning medical history, the Charlson Comorbidity Index (CCI) and the hospital stay, including length, drugs and COVID-19 complications (respiratory failure, lung involvement, and the need for respiratory support) were collected, as well as the type of discharge. Results: patients with asthma required high-flow oxygen therapy (33.3 vs. 14.3%, p = 0.001) and invasive mechanical ventilation (17.9 vs. 9.5%, p = 0.048) more frequently when compared to the general population, but no other difference was observed. Moreover, asthma patients were generally younger than patients with COPD (59.2 vs. 76.8 years, p < 0.001), they showed both a lower mortality rate (15.4 vs. 39.4%, p < 0.001) and a lower CCI (3.4 vs. 6.2, p < 0.001). Patients with asthma in regular therapy with ICS at home had significantly shorter hospital stay compared to those with no treatments (25.2 vs. 11.3 days, p = 0.024). Discussion: Our study showed that asthma is not associated with worse outcomes of COVID-19, despite the higher need for respiratory support compared with the general population, while the use of ICS allowed for a shorter hospital stay. In addition, the comparison of asthma with COPD patients confirmed the greater frailty of the latter, according to their multiple comorbidities.