Association Between Changes in BLyS Levels and the Composition of B and T Cell Compartments in Patients With Refractory Systemic Lupus Erythematosus Treated With Belimumab

Introduction: Belimumab is a monoclonal antibody against soluble BLyS used for treatment of refractory Systemic Lupus Erythematosus (SLE). Although B cells are the main target of this therapy, a BLyS-dependent T cell activation pathway has also been demonstrated. The aim of the study is to analyze B and T cells phenotype modifications in a cohort of SLE patients treated with belimumab in correlation with serum BLyS levels.Materials and Methods: Fourteen SLE patients were enrolled in the study. Lymphocyte immunophenotyping by flow cytometry and determination of serum BLyS levels by high sensitivity ELISA were performed before the first infusion of belimumab, after 6 and 12 months of treatment. Sex and age-matched healthy controls were enrolled for the comparisons.Results: Baseline number of total B cells, especially switched memory B cells, were lower in SLE patients compared to control subjects. After 6 months of treatment, the total number of B cells, particularly, naive and transitional B cells, was significantly reduced in correlation with the reduction of BLyS levels. No significant association was found between baseline counts of B cells and reduction of SLEDAI-2K over time. In terms of response prediction, a significant association between SLEDAI-2K improvement at 12 months and the decrease of total number of B cells within the first 6 months of therapy was observed. Concerning the T cell compartment, the baseline percentage number of CD8+ effector memory was associated with SLEDAI-2K at baseline and with its improvement after 12 months of therapy. Furthermore, T cell lymphopenia and low number of circulating recent thymic emigrants were also observed compared to control subjects measured at baseline.Discussion: The effects of belimumab on B cell subpopulations could be explained by the direct blockage of soluble BLyS, while the mild effects on T cells might be explained indirectly by the reduction of disease activity by means of therapy. B cell immunophenotyping during belimumab might be useful for monitoring the response to treatment

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments

Switching from Intravenous to Subcutaneous Formulation of Abatacept: A Single-center Italian Experience on Efficacy and Safety

Subcutaneous (SC) abatacept (ABA) is comparable to intravenous (IV) formulation in terms of efficacy and safety profile. Our work analyzed the switch to SC formulation from IV administration in patients with rheumatoid arthritis

Pregnancy implications for systemic lupus erythematosus and the antiphospholipid syndrome

Multidisciplinary approach and patient counselling have been the key points in the improvement of the management of pregnancy in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Most of these women can have successful pregnancy when thoroughly informed and instructed on several different issues. Disease activity should be in stable remission prior to pregnancy in order to reduce the chance for flare during pregnancy. To this purpose, medications must be modulated: "safe" drugs should be continued throughout pregnancy, embryotoxic/foetotoxic drugs should be withdrawn timely, and beneficial drugs such as low dose aspirin and heparin should be added for prophylaxis of maternal and foetal outcome, especially in the presence of antiphospholipid antibodies. The safety profile of anti-rheumatic drugs during pregnancy and breastfeeding should be kept constantly updated, as new data from inadvertent exposure accumulates and new drugs (especially biological agents) are available. Patients may carry autoantibodies that can negatively affect the baby, being neonatal lupus the prototypical case of passively acquired autoimmunity. Research has been greatly active in this field and more information on risk stratification and management are now available for counselling. The effect of both autoantibodies and drug exposure has been evaluated in the offspring: some concerns about learning disabilities have been raised, but these are treatable conditions that are likely to be overcome. To counsel a woman with SLE/APS during childbearing age means also to deal with contraception. Despite the "preferred choice" - combined oral contraceptive - may not be suitable for most of the patients, other options are available and should be offered and discussed with the patient. Fertility is not generally affected in SLE/APS patients, but those cases who require assisted reproduction techniques should be carefully evaluated and managed

The role of second trimester uterine artery Doppler in pregnancies with systemic lupus erythematosus

OBJECTIVE: To assess the predictive value of second trimester mean uterine artery Doppler pulsatility-index (mUtA PI) for pregnancy complications in women with systemic lupus erythematosus (SLE). METHODS: Cohort study of consecutive pregnancies complicated with SLE during a 12 years period. SLE diagnosis was made before pregnancy. mUtA PI was measured between 23 + 0 and 26 + 6 weeks' gestation. Pregnancy and neonatal outcomes were collected. Small for gestational age (SGA) was defined as birth weight <10th percentile. Adverse pregnancy outcome (APO) was defined as one of the following: pre-eclampsia, SGA, placental abruption, stillbirth or neonatal death. Differential diagnosis between pre-eclampsia and renal flare was made according to SLE-disease activity index (SLEDAI) index. RESULTS: 70 pregnancies in 64 women. Pre-eclampsia was observed in 4 cases (6%), SGA in 5 (7%) and APO in 7 (10%). mUtA PI showed a sensitivity and a specificity of 1.0 (95% CI 0.5-1.0) and 1.0 (95% CI 0.95-1.0) for pre-eclampsia, 0.40 (95% CI 0.12-0.77) and 0.97 (95% CI 0.89-0.99) for SGA, 0.57 (95% CI 0.25-0.84) and 1.0 (95% CI 0.94-1.0) for APO, respectively. CONCLUSION: Our findings suggest that uterine artery Doppler is confirmed to be a high sensitivity and high specificity test for predicting pre-eclampsia even in SLE patients

The role of second trimester uterine artery Doppler in pregnancies with systemic lupus erythematosus

OBJECTIVE: The aim of this article is to assess the predictive value of second trimester mean uterine artery Doppler pulsatility index (mUtA PI) for pregnancy complications in women with systemic lupus erythematosus (SLE). METHODS: Cohort study of consecutive pregnancies complicated with SLE during a period of 12 years is used. SLE diagnosis was made before pregnancy. mUtA PI was measured between 23 + 0 and 26 + 6 weeks' gestation. Pregnancy and neonatal outcomes were collected. Small for gestational age (SGA) was defined as birth weight &lt;10th percentile. Adverse pregnancy outcome (APO) was defined as one of the following: pre-eclampsia (PE), SGA, placental abruption, stillbirth, or neonatal death. Differential diagnosis between PE and renal flare was made according to SLE-disease activity index. RESULTS: There are 70 pregnancies in 64 women. PE was observed in four cases (6%), SGA in five cases (7%), and APO in seven cases (10%). mUtA PI showed a sensitivity and a specificity of 1.0 (95% CI 0.5-1.0) and 1.0 (95% CI 0.95-1.0) for PE, 0.40 (95% CI 0.12-0.77) and 0.97 (95% CI 0.89-0.99) for SGA, and 0.57 (95% CI 0.25-0.84) and 1.0 (95% CI 0.94-1.0) for APO, respectively. CONCLUSION: Our findings suggest that uterine artery Doppler is confirmed to be a high sensitivity and a high specificity test for predicting PE even in SLE patients