Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, variable airflow obstruction, and persistent inflammation. While its pathophysiology is well established, growing evidence highlights significant sex-based differences in its prevalence, severity, and treatment response. Epidemiological studies indicate that asthma is more common in prepubertal boys but shifts toward a female predominance after puberty, with adult women experiencing higher morbidity and greater healthcare utilization. These disparities suggest a crucial role for sex hormones, genetic predisposition, and epigenetic regulation in asthma pathogenesis. Sex hormones modulate immune responses, contributing to disease progression. Estrogen enhances type 2 inflammation, increases eosinophilic infiltration, and upregulates IL-4 and IL-13 expression, leading to greater airway hyperreactivity in women. Additionally, progesterone fluctuations correlate with perimenstrual asthma exacerbations, while testosterone appears to exert a protective effect by dampening Th2-driven inflammation and airway remodeling. These hormonal influences contribute to sex-specific asthma phenotypes and treatment responses. Genetic and epigenetic factors further shape sex-related differences in asthma. The X chromosome harbors immune-regulatory genes, including TLR7 and TLR8, which amplify inflammatory responses in females. The sex-dependent expression of IL13 and ORMDL3 influences eosinophilic inflammation and airway remodeling. Epigenetic modifications, such as DNA methylation and microRNA regulation, further impact immune activation and corticosteroid responsiveness. For instance, Let-7 miRNAs modulate IL-13 expression, contributing to sex-specific inflammatory profiles. Environmental factors, including air pollution, obesity, and diet, interact with hormonal and genetic influences, exacerbating sex disparities in asthma severity. Obesity-related metabolic dysfunction promotes systemic inflammation, airway remodeling, and steroid resistance, disproportionately affecting women. Given these complex interactions, sex-specific approaches to asthma management are essential. Personalized treatment strategies targeting hormonal pathways, immune regulation, and metabolic health may improve outcomes for both men and women with asthma. Future research should focus on sex-based therapeutic interventions to optimize disease control and mitigate healthcare disparities.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by a variety of both signs and symptoms; it mainly affects women of childbearing age, with an estimated prevalence of 24/100,000 people in Europe and North America. SLE is often described as an antibodies-driven disease as its clinical manifestations are usually associated with the presence or the absence of specific antibodies.Objectives: To evaluate clinical manifestations in patients with SLE and to assess the relationship with the presence of specific antibodies by using real-world data.Methods: A retrospective study was performed; the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus were used to classify patients with SLE. Data concerning serological profiles (which included Antinuclear antibodies – ANA, anti dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-Smith) were gathered along with medical records of clinical manifestations. Complement levels were also tested for possible clinical correlations. χ² or Fisher’s exact tests were utilized to establish associations between autoantibodies and symptoms. The odds ratios (OR) and their 95% confidence intervals (CI) were computed. No correction was made for multiple testing; only a p-value 0.01 ≤ was considered significant.Results: One-hundred and twenty-seven patients (n=127, mean age 53.43 ± 14.02) were enrolled in this study. Anti-dsDNA antibodies were found to be statistically significant for both malar rash and proteinuria; anti-Ro/SSA antibodies showed an association with photosensitivity and pericarditis; furthermore, a strong association was found between anti-Ro antibodies and proteinuria, but only if anti-dsDNA antibodies were present as well. Patients who tested positive for anti-La/SSB antibodies correlated with a threefold increase in the risk of developing pericarditis. Lastly, anti-Smith appeared to be associated with NPSLE as well as an increased risk for both autoimmune hemolytic anemia and thrombocytopenia.Conclusions: In our study, many associations confirmed those found in previous studies; however, new relationships between antibodies and clinical manifestations were found thus indicating the need for additional evaluations to assess these correlations further.

HCV is a virus that can cause chronic infection which can result in a systemic disease that may include many rheumatologic manifestations such as arthritis, myalgia, sicca syndrome, cryoglobulinemia vasculitis as well as other non-rheumatological disorders (renal failure, onco-haematological malignancies). In this population, the high frequency of rheumatoid factor (45–70%), antinuclear (10–40%) and anticardiolipin (15–20%) antibodies is a B-cell mediated finding sustained by the infection. However, the possibility that a primitive rheumatic pathology may coexist with the HCV infection is not to be excluded thus complicating a differential diagnosis between primitive and HCV-related disorders.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease which causes pain and functional impairment in adults over 50 years old with consequent important disability. Unfortunately, there is no definitive cure for OA, thus the approach is characterized by multiple treatments that can manage its symptoms. Even though data from randomized controlled trials and meta-analyses indicate that intra-articular hyaluronic acid (IAHA) offers the best benefit/risk balance among the various pharmacologic treatments to improve OA-related knee pain, there is a lack of agreement among national and international guidelines about such uses of IAHA for the medical management of symptomatic knee OA. To minimize confounding factors and biases, the aim of our study was to evaluate the efficacy of the different weight and concentration of IAHA treatment in patients suffering from knee OA comparing to glucocorticoids (GC) joint injections. Furthermore, to make the procedure more accurate and assessment more objective, we use ultrasonography (US) with power Doppler (PWD) to help us differentiate between active and inactive inflammation within joints and periarticular soft tissues. METHODS: We performed a retrospective evaluation of a cohort of patients with knee OA, diagnosed according to the ACR criteria, treated by US-guided joint injection of HA and GC. The patients were catalogued according to the type of treatment they underwent: group A, patients treated with HA (1.5%) >1500 kDa (three US-guided knee injections one week apart); group B, patients treated with HA (2%) 800-1200 kDa (three US-guided knee injections one week apart); group C, patients treated with glucocorticoids (three US-guided knee injections of triamcinolone acetate 40 mg one week apart). All patients were monitored for 6 months, evaluating: subjective pain using a 10-cm Visual Analogue Scale; pain, stiffness, and functionality using the Western Ontario and McMaster Universities Arthritis Index (WOMAC); the concomitant intake of anti-inflammatory and/or analgesic drugs through a questionnaire; and US results by grey scale and PWD. RESULTS: A total of 171 patients affected by knee OA were evaluated (women 72.3%) with a mean age of 69.3 +/- 4.1 years. All the subjects analyzed showed a pain reduction at 6 months after treatment (group A: -39.5; group B: -36.9; group C: -30.8). The difference between the three groups was statistically significant (Kruskall-Wallis P=0.001) and in particular between group A and group C (P=0.000) and between group B and group C (P=0.005), but not between A and B (P=0.258). WOMAC was statistically significantly improved from baseline in all groups examined (group A: -11.9; group B: -14.9; group C: -11.2). The PWD score showed a statistically significant improvement in group B (-0.64) even after 6 months (P=0.004). All patients in the different groups showed a statistically significant reduction of concomitant therapy compared to baseline with respect to paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs)/COX2 therapy, while only group B showed a statistically significant reduction for opioids. CONCLUSIONS: This study demonstrated the efficacy of OA treatment with medium molecular weight HA in favor of the higher concentration of HA that may affect the reduction of pro-inflammatory mediators. Furthermore, US monitoring allowed to evaluate aspects related to synovial involvement, which cannot be appreciated with standard imaging.

Bispecific antibodies (bsAbs) have emerged as one of the most versatile innovations in immunotherapy, capable of simultaneously engaging two distinct epitopes within a single molecule and thereby expanding the functional repertoire of conventional monoclonal antibodies. Their capacity to integrate checkpoint blockade, co-stimulatory activation and cytokine modulation renders them particularly attractive in conditions driven by dysregulated or redundant immune pathways, including cancer, autoimmunity, chronic inflammation and infectious diseases. Technological advances such as knobs-into-holes, dual-affinity retargeting (DART) constructs and IgG-like asymmetric designs have refined stability, pharmacokinetics and manufacturability, enabling clinical translation beyond oncology. Nevertheless, significant challenges remain, including immunogenicity, cytokine release syndrome, neurotoxicity and adaptive resistance mediated by antigen modulation or tissue microenvironmental adaptation. To mitigate these, innovative approaches, ranging from protease-activatable constructs and Fc engineering to albumin-binding fusion proteins and bispecific antibody-drug conjugates, are under active investigation. In addition, bsAbs are being integrated with other immunomodulatory strategies such as CAR-T cells, therapeutic vaccines and checkpoint inhibitors, offering the potential for synergistic benefit across diverse immune-mediated diseases. In this review, we chart the trajectory of bsAb development from molecular design to clinical translation in cancer and immune regulation. We highlight structural optimisation, pharmacokinetic tuning and mechanisms of immune regulation, aiming to provide a framework for their rational use in reshaping immune response in cancer and beyond.