Interstitial lung disease (ILD) is a life-threatening complication of systemic sclerosis (SSc). Type 2 (Th2) cytokines play a pivotal role in airway disease. Study aim was to evaluate serum level of Th2 interleukin (IL) and chemokine in SSc-ILD. Serum levels of IL-4, IL-5, IL-11, IL-13, IL-21, IL-31 and CXCL-13 were measured by Bio-Plex Multiplex Immunoassays in 60 SSc patients and 20 healthy controls (HC). Pulmonary function tests with diffusion lung capacity for carbon monoxide (DLco) and high resolution computed tomography (HRCT) were performed in SSc patients. ILD is defined as fibrotic changes (ground glass, reticular and honeycombing), assessed by Computer-Aided Lung Informatics for Pathology Evaluation and Ratings (CALIPER) software, affecting at least 10% of the lungs. Serum levels of Th2 cytokines were higher in SSc patients than HC. A linear correlation was observed between ground glass and IL-13 (r = 0.342, p < 0.01), IL-21 (r = 0.345, p < 0.01), IL-31 (r = 0.473, p < 0.001), IL-4 (r = 0.863, p < 0.001), IL-5 (r = 0.249, p < 0.05) and peripheral blood eosinophils (r = 0.463, p < 0.001). We found a negative correlation between DLco and IL-4 (r =  − 0.511, p < 0.001) and peripheral blood eosinophils (r =  − 0.446, p < 0.001). In the logistic regression analysis, IL-4 is associated with DLco ≤ 60% of the predicted [OR 1.039 (CI 95%: 1.015–1.064), p < 0.001], whilst mRSS [OR 1.138 (CI 95%: 1.023–1.266), p < 0.05] and IL-4 [OR 1.017 (CI 95%: 1–1.034), p < 0.05] were associated with ILD. Th2 inflammation could play a key role in early phase of SSc-ILD.

Edoardo Rosato and Umberto Basile jointly supervised this work.

Objectives The biomarkers of an immunological dysregulation due to a chronic Hepatitis B virus (HBV) infection are indeed understudied. If untreated, this condition may evolve into liver impairment also co-occurred by extrahepatic involvements. Here, we aim to identify a new panel of biomarkers including IgG subclasses, Rheumatoid Factor (RF), and Free Light Chains (FLC) that may result useful and reliable for clinical evaluation of HBV-related cryoglobulinemia. Methods We retrospectively analyzed clinical data from 44 HBV positive patients. Patients were stratified on the presence/absence of mixed cryoglobulinemia in two group: 22 with cryoglobulins (CGs) and 22 without CGs. Samples from 20 healthy blood donors (HD) were used as negative controls. Serum samples were tested for IgG subclasses, RF (IgM, IgG, and IgA type), and FLC. Results We detected a strikingly different serum IgG subclasses distribution between HD and HBV positive patients together with different RF isotypes; FLC were significantly increased in HBV-patients if compared with HD while no significant difference was shown between HBV with/without MC. Conclusion The immune-inflammatory response triggered by HBV may be monitored by a peculiar profile of biomarkers. Our results open new perspective in precision medicine era; in these challenging times, they could be also employed to monitor the clinical course of COVID-19 patients, at high risk of HBV reactivation due to liver impairment and/or immunosuppressive therapies.

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Introduction: The involvement of complement system in the phenotypic expression of systemic sclerosis (SSc) is a debated topic. We aimed to assay complement fractions in SSc patients and to correlate their levels with the clinical course of disease. Key points: 1. CH50 is increased in SSc patients compared to HC; 2. Serum C2 levels are increased in SSc patients compared to HC; 3. CH50 may represent a biomarker of skin and lung fibrosis severity in SSc patients. Method: Complement hemolysis 50% (CH50), C2, C3 and C4 levels have been assessed in 85 SSc patients and 47 healthy controls (HC). Results: SSc patients displayed a statistically significant higher value of CH50 [76.3 U/mL (IQR 65.8–89.4 U/mL) vs. 29.6 U/mL (IQR 24.7–34 U/mL); p < 0.0001] and of C2 [26.1 mg/L (IQR 24.1–32.1 mg/L) vs. 22.7 mg/L (IQR 20.6–24.4 mg/L); p < 0.0001] if compared to HC. Patients with diffuse cutaneous SSc (dcSSc) had higher levels of CH50 than patients with limited cutaneous SSc (lcSSc) [83.6 U/mL (IQR 72.3–102.7 U/mL) vs. 71.3 U/mL (IQR 63.7–83.6 U/mL); p = 0.003]. SSc patients with interstitial lung disease (ILD) had higher CH50 levels if compared to SSc patients without ILD [79.6 U/mL (IQR 68.3–97.4 U/mL) vs. 69.7 U/mL (54.6–85.7 U/mL); p = 0.042]. A positive linear correlation existed between CH50 and the modified Rodnan Skin Score (mRSS) (r = 0.285, p = 0.008) and disease severity scale (DSS) (r = 0.285, p = 0.005); a negative linear correlation was demonstrated between CH50 and the diffusing capacity of carbon monoxide (DLco) (r = −0.252, p = 0.012). In multiple linear regression analysis, only DSS was significant (p = 0.01, beta coefficient 2.446). Conclusions: Our results show an increment of CH50 and serum C2 levels in SSc patients in comparison to HC; we retain that CH50 may represent a biomarker of disease severity and of skin and lung fibrosis in these patients.