Francesca Wanda Rossi

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organs and systems with a broad and heterogeneous spectrum of clinical manifestations. National disease-specific datasets and registries are crucial for clinical research since they can provide real-world and long-term data about clinical aspects, biomarkers, and treatments. Registries collect data from actual patients over time, outside the controlled environment of randomized controlled trials. This can help enhance the understanding of the natural history of a disease, provide information about how treatments work in everyday settings and elucidate potential variations in care and outcomes across different geographic areas. Here, we present a protocol for the creation of a standardized national disease-specific dataset for patients with SLE—the Systemic Lupus Erythematous Network (LUNET) Registry—which will facilitate data sharing, cross-comparison, and interoperability among centers. The LUNET registry is intended to serve as a comprehensive primary data source, capturing real-world longitudinal clinical information and the heterogeneity of patient presentations that are often underrepresented in traditional clinical trials. Ultimately, the LUNET registry will help to optimize SLE management in routine clinical practice by enabling the compilation of real-world evidence to inform clinical decision-making and health policy.

Systemic lupus erythematosus (SLE) is a pleiotropic disease that can present in numerous forms, ranging from mild mucocutaneous symptoms to severe manifestations affecting multiple organs. SLE has the potential to impact any segment of the respiratory system, exhibiting a range of severity levels throughout the different stages of the disease. Pulmonary manifestations in SLE patients can be classified as primary (i.e., directly related to SLE and to immune-mediated damage), secondary to other SLE manifestations (e.g., nephrotic syndrome, renal failure, congestive heart failure), and comorbidities (e.g., infections, cancers, overlapping primary respiratory diseases). Understanding and correctly managing lung involvement in SLE is crucial because pulmonary complications are common and can significantly impact morbidity and mortality in affected patients. Early recognition and appropriate treatment can prevent irreversible lung damage, improve quality of life, and reduce the risk of life-threatening complications. Treatment algorithms are based on the suppression of inflammation, with or without the need for dedicated, supportive care. According to disease severity, available treatments include nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants, and biological agents. In this review, we aim to summarize the current knowledge on lung involvement in SLE and then focus on the management and treatment approaches available for the different forms.

Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES—Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches.

Systemic Sclerosis (SSc) is a heterogeneous autoimmune disease characterized by widespread vasculopathy, the presence of autoantibodies and the progressive fibrosis of skin and visceral organs. There are still many questions about its pathogenesis, particularly related to the complex regulation of the fibrotic process, and to the factors that trigger its onset. Our recent studies supported a key role of N-formyl peptide receptors (FPRs) and their crosstalk with uPAR in the fibrotic phase of the disease. Here, we found that dermal fibroblasts acquire a proliferative phenotype after the activation of FPRs and their interaction with uPAR, leading to both Rac1 and ERK activation, c-Myc phosphorylation and Cyclin D1 upregulation which drive cell cycle progression. The comparison between normal and SSc fibroblasts reveals that SSc fibroblasts exhibit a higher proliferative rate than healthy control, suggesting that an altered fibroblast proliferation could contribute to the initiation and progression of the fibrotic process. Finally, a synthetic compound targeting the FPRs/uPAR interaction significantly inhibits SSc fibroblast proliferation, paving the way for the development of new targeted therapies in fibrotic diseases.

Natural products (water, plants, and minerals) have been studied for diverse applications in health and disease. Since there has been a growing interest in the introduction of thermal water as a clinical complementary approach in the treatment of low-grade inflammation and stress-related conditions, this review focuses on the oldest spa in the world: Nitrodi’s spring. Substantial studies in the 1960s showed that both the internal and external use of Nitrodi’s water yielded several benefits in physiological processes and in treating certain disorders, mainly allergic and autoimmune inflammatory conditions. More recently, a novel interest in Nitrodi’s water has prompted researchers to further explore the effects of this water and shed light on the molecular mechanisms sustaining its therapeutic efficacy. In different epithelial cell models, Nitrodi’s water had strong promotional effects on proliferation, cell migration, cell viability, and fibroblast to myofibroblast transition, all of which essential for wound healing and tissue remodeling. Moreover, Nitrodi’s water exhibited anti-oxidant and anti-inflammatory properties through the inhibition of ROS production and protein S-nitrosylation. Here, we have collected the clinical and basic data on Nitrodi’s water and reviewed articles that have discussed its use as a potential treatment for several inflammatory and autoimmune diseases and age-related skin deterioration.

Neurologic manifestations have been occasionally described in patients with bradykinin-mediated angioedema. The existing literature is currently limited to case series and case reports mainly described in the hereditary forms (HAE) concerning central nervous system (CNS) involvement. On the contrary, very little is known about peripheral and autonomic nervous system manifestations. CNS involvement in HAE may present with symptoms including severe headaches, visual disturbance, seizures, and various focal and generalized deficits. In addition, a stroke-like clinical picture may present in HAE patients. In turn, some drugs used in patients with cardiovascular and neurologic disorders, such as recombinant tissue plasminogen activator (r-tPA) and angiotensin-converting enzyme inhibitors (ACEI), may produce medication-induced angioedema, resulting in a diagnostic challenge. Finally, most patients with HAE have higher levels of psychological distress, anxiety, and depression. With this review, we aimed to provide an organized and detailed analysis of the existing literature on neurologic and psychiatric manifestations of HAE to shed light on these potentially invalidating symptoms and lay the foundation for further personalized diagnostic pathways for patients affected by this protean disease.

Eosinophils play a key role in airway inflammation in many diseases, such as allergic and non-allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic obstructive pulmonary disease. In these chronic disabling conditions, eosinophils contribute to tissue damage, repair, remodeling, and disease persistence through the production a variety of mediators. With the introduction of biological drugs for the treatment of these respiratory diseases, the classification of patients based on clinical characteristics (phenotype) and pathobiological mechanisms (endotype) has become mandatory. This need is particularly evident in severe asthma, where, despite the great scientific efforts to understand the immunological pathways underlying clinical phenotypes, the identification of specific biomarkers defining endotypes or predicting pharmacological response remains unsatisfied. In addition, a significant heterogeneity also exists among patients with other airway diseases. In this review, we describe some of the immunological differences in eosinophilic airway inflammation associated with severe asthma and other airway diseases and how these factors might influence the clinical presentation, with the aim of clarifying when eosinophils play a key pathogenic role and, therefore, represent the preferred therapeutic target.

The Romans knew of Nitrodi’s spring on the island of Ischia more than 2000 years ago. Although the health benefits attributed to Nitrodi’s water are numerous, the underlying mechanisms are still not understood. In this study, we aim to analyze the physicochemical properties and biological effects of Nitrodi’s water on human dermal fibroblasts to determine whether the water exerts in vitro effects that could be relevant to skin wound healing. The results obtained from the study indicate that Nitrodi’s water exerts strong promotional effects on dermal fibroblast viability and a significant stimulatory activity on cell migration. Nitrodi’s water induces alpha-SMA expression in dermal fibroblasts, thus promoting their transition to myofibroblast-protein ECM deposition. Furthermore, Nitrodi’s water reduces intracellular reactive oxygen species (ROS), which play an important role in human skin aging and dermal damage. Unsurprisingly, Nitrodi’s water has significant stimulatory effects on the cell proliferation of epidermal keratinocytes and inhibits the basal ROS production but enhances their response to the oxidative stress caused by external stimuli. Our results will contribute to the development of human clinical trials and further in vitro studies to identify inorganic and/or organic compounds responsible for pharmacological effects.

Many factors may trigger hereditary angioedema (HAE) attacks. This study aims to gain insights into the benefits and potential risks of COVID-19 vaccination in HAE patients, focusing particularly on the possibility of triggering attacks. We enrolled 31 patients with HAE undergoing two doses of the SARS-CoV-2 mRNA Comirnaty-BioNTech/Pfizer vaccine. To evaluate the possible influence of the vaccine on disease control and attack frequency, we administered the angioedema control test (AECT) 4-week version before (T0), 21 days after the first dose (T1), and between 21 and 28 days after the second dose (T2). Despite 5 patients (16.1%) experiencing attacks within 72 h of the first dose administration, no significant variation in attack frequency was observed before and after vaccination [F(2,60) = 0.123; p = 0.799]. In addition, patients reported higher AECT scores at T1 and T2 compared to T0 [F(2,44) = 6.541; p < 0.05; post hoc p < 0.05)], indicating that the disease was rather more controlled after vaccinations than in the previous period. All patients showed a positive serological response to the vaccine without significant differences from healthy controls (U = 162; p = 0.062). These observations suggest that the vaccine administration is safe and effective in HAE patients.

Cancer-related inflammation has recently emerged as an important component of cancer pathogenesis that is able to promote tumor initiation and progression, and the acquisition of the known hallmark capabilities, including evasion from immunosurveillance. Several soluble and cellular mediators participate in tumor microenvironment formation, leading to cancer initiation and progression. In this view, Tumor-Associated Macrophages (TAMs) are pivotal players and, due to their characteristic plasticity, can acquire a variety of distinct phenotypes and contribute in different ways to the different phases of carcinogenesis. Different stimuli have been shown to modulate macrophage polarization. Secreted phospholipase A₂ enzymes (sPLA₂s) exert multiple biological effects on cancer-related inflammation due to their enzymatic activity and ability to activate inflammatory cells by non-enzymatic mechanisms. Among the different sPLA₂ isoforms, several studies have suggested that group IIA and group X are mainly involved in a wide variety of cancer types. A deeper insight into the molecular mechanisms regulating the link between tumor-infiltrating immune cells and cancer could lead to identifying new prognostic/predictive biomarkers and a broader view of cancer immunotherapy.