Long-term outcome of autologous haematopoietic stem cell transplantation in patients with systemic sclerosis: a comparison with patients treated with rituximab and with traditional immunosuppressive agents.

Background: Autologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there is still a paucity of data comparing AHSCT with rituximab (RTX). Aim of the study is to retrospectively compare, in patients with dcSSc, the effectiveness of AHSCT with that of RTX and CIT.

Overexpression of BAG3 (Bcl2-associated athanogene 3) in serum and skin of patients with systemic sclerosis.

Objectives: BAG3 (Bcl2-associated athanogene3) is able to induce the transformation of cancer-associated fibroblasts to alpha smooth muscle actin (a-SMA) positive (+) myofibroblasts. In systemic sclerosis (SSc), a-SMA+ myofibroblasts also play an important role in the progression of fibrosis in the skin and involved internal organs. The aim of the study was to investigate whether BAG3 is overexpressed in SSc and may be a biomarker of fibrogenesis.

Cellular-Based Therapies in Systemic Sclerosis: From Hematopoietic Stem Cell Transplant to Innovative Approaches.

Systemic sclerosis (SSc) is a systemic disease characterized by autoimmune responses, vasculopathy and tissue fibrosis. The pathogenic mechanisms involve a wide range of cells and soluble factors. The complexity of interactions leads to heterogeneous clinical features in terms of the extent, severity, and rate of progression of skin fibrosis and internal organ involvement.

Instruments for Outcome Evaluation of Specific Domains in Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterized by very heterogeneous features. The spectrum of this disorder may vary from benign but disabling symptoms such as dryness, due to lachrymal and salivary involvement, pain and fatigue, to systemic, potentially severe, manifestations that may involve any organ. In recent decades, the arrival of biotechnological therapy has offered new opportunities for the treatment of this-until now-orphan disease.

Management of Sjögren's Syndrome: Present Issues and Future Perspectives.

In view of the new possibilities for the treatment of primary Sjögren's syndrome (pSS) given by the availability of new biotechnological agents targeting the various molecular and cellular actors of the pathological process of the disease, classification criteria aimed at selecting patients to be enrolled in therapeutic trials, and validated outcome measures to be used as response criteria to these new therapies, have been developed and validated in the last decades. Unfortunately, the therapeutic trials so far completed with these new treatments have yielded unsatisfactory or only partially positive results. The main issues that have been evoked to justify the poor results of the new therapeutic attempts are: (i) the extreme variability of the disease phenotypes of the patients enrolled in the trials, which are dependent on different underlying patterns of biological mechanisms, (ii) the fact that the disease has a long indolent course, and that most of the enrolled patients might already have irreversible clinical features.

The Role of Interferons in the Pathogenesis of Sjögren's Syndrome and Future Therapeutic Perspectives.

There is a great deal of evidence pointing to interferons (IFNs) as being key cytokines in the pathogenesis of different systemic autoimmune diseases, including primary Sjögren's syndrome (pSS). In this disease, a large number of studies have shown that an overexpression of type I IFN, the 'so-called' type I IFN signature, is present in peripheral blood mononuclear cells, and that this finding is associated with the development of systemic extra-glandular manifestations, and a substantial production of autoantibodies and inflammatory cytokines. In contrast, the absence or a milder expression of type I IFN signature and low level of inflammatory cytokines characterizes patients with a different clinical phenotype, where the disease is limited to glandular involvement and often marked by the presence of widespread pain and depression.

Autophagy occurs in lymphocytes infiltrating Sjögren's syndrome minor salivary glands and correlates with histological severity of salivary gland lesions.

Backgrounds: The organization of minor salivary glands (MSG) infiltrates, in patients with Sjögren's syndrome (SS), associates with disease severity and progression. Aberrant regulation of lymphocyte autophagy is involved in autoimmunity, and in previous work, we provided the first evidence of upregulated autophagy in CD4+ T cells infiltrating SS MSG. The aim of this study was to further explore autophagy in SS infiltrating and circulating lymphocytes and to investigate its role in disease histopathological progression.

High NEMO score values in nailfold videocapillaroscopy are associated with the subsequent development of ischaemic digital ulcers in patients with systemic sclerosis.

Background: Nailfold videocapillaroscopy (NVC) is a feasible method that allows the observation of the microvascular changes that mark the course of systemic sclerosis (SSc). In previous studies, we demonstrated that the NEMO score, i.e.

Impact of COVID-19 outbreak in an Italian cohort of patients with systemic sclerosis.

Background: Mortality rate in patients infected by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can be related to the presence of comorbidities like diabetes, cardiovascular and pulmonary diseases. On the contrary, few data exist on the impact of CoronaVirus Disease 2019 (COVID-19) on patients with rheumatic disorders, namely in those having pulmonary involvement and treated with immunosuppressive agents. The present survey is aimed at knowing the impact of COVID-19 in a cohort of patients with systemic sclerosis (SSc).

Taking care of systemic sclerosis patients during COVID-19 pandemic: rethink the clinical activity.

COVID-19 outbreak has quickly spread worldwide, causing a high pressure on the health-care system. In Italy, from March 8, 2020, all the deferrable clinical activities have been suspended to increase the health care offer for COVID-19 patients. The hospital organization has been modified also in order to assure non-COVID-19 patients assistance.

Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjögren's syndrome.

Objective: To characterize the systemic phenotype of primary Sjögren's syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores.

Methods: The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren's syndrome from the five continents.

Results: The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available.

Gene Expression Profiles in Primary Sjögren's Syndrome With and Without Systemic Manifestations.

Objective: To investigate the gene expression profile in patients with Sjögren's syndrome that is characterized by different clinical phenotypes.

Methods: RNA from peripheral blood mononuclear cells was purified in 8 patients with glandular features (GFs) and widespread pain (WP) and 11 with extraglandular manifestations (EGMs) and then was analyzed by hybridization on a human gene chip exploring more than 40,000 human genes. Differentially expressed genes (DEGs) in the two subgroups (ie, those with false discovery rate-corrected values ≤ 0.

NEMO score in nailfold videocapillaroscopy is a good tool to assess both steady state levels and overtime changes of disease activity in patients with systemic sclerosis: a comparison with the proposed composite indices for this disease status entity.

Background: In previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages (MHEs) and microthromboses (MTs), observed in nailfold videocapillaroscopy was a good indicator of the steady state level of disease activity (DA) in patients with systemic sclerosis (SSc) when the European Scleroderma Study Group (EScSG) index was considered the gold standard.

CXCL13 as biomarker for histological involvement in Sjögren's syndrome.

Objectives: SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres' formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres' activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation.

First Report of the Italian Registry on Immune-Mediated Congenital Heart Block (Lu.Ne Registry).

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. 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) or neonatal period (up to 27 days after birth).

Regional grafting of autologous adipose tissue is effective in inducing prompt healing of indolent digital ulcers in patients with systemic sclerosis: results of a monocentric randomized controlled study.

Background: A randomized controlled trial (RCT) was performed to confirm preliminary uncontrolled data indicating that regional adipose tissue (AT) grafting (G) is effective in inducing ischemic digital ulcer (IDU) healing in patients with systemic sclerosis (SSc).

Patients And Methods: SSc patients with IDUs were randomized to be blindly treated with AT-G or a sham procedure (SP). AT-G consisted of injection, at the base of the finger with the IDU, of 0.

Autologous Hematopoietic Stem Cell Transplantation for Treatment of Systemic Sclerosis.

Systemic Sclerosis (SSc) is a complex autoimmune disease, characterized by high mortality and morbidity. The heterogeneity in terms of extent, severity, and rate of progression of skin and internal organ involvement gives rise to many difficulties in finding the optimal therapeutic interventions for SSc and, to date, no disease-modifying agents are available. In this scenario, it is not surprising that SSc was one of the first autoimmune diseases challenged with high-dose immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (AHSCT).

CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren's syndrome patients and correlates with focus score and disease activity.

Background: Primary Sjögren's syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS.

Methods: Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome and/or chronic sialoadenitis and 30 healthy controls.

Sleep quality in patients with primary Sjögren's syndrome.

Objectives: To assess the sleep quality in primary Sjögren's syndrome (pSS) patients and evaluate its relationship with the disease, quality of life and mood disorders.

Methods: The sleep quality of 29 pSS women and 29 matched controls was assessed by the Pittsburgh Sleep Quality Index (PSQI). Seven domains are grouped according to three factors: F1 perceived sleep quality (subjective sleep quality, sleep latency, use of sleeping medication), F2 sleep efficiency (sleep duration, habitual sleep efficiency) and F3 daily disturbances (sleep disturbances, daytime dysfunction).

Quality of Sexual Life in Women with Primary Sjögren Syndrome.

Objective: To assess the quality of sexual life of women with primary Sjögren syndrome (pSS) and to identify its correlations with disease activity and damage, quality of life, and mood disorders.

Methods: The quality of sexual life of 24 women with pSS was assessed with the Female Sexual Function Index (FSFI). Twenty-four healthy women, matched by age and hormonal status, were enrolled as controls.