Objectives: Oesophageal dysmotility is a common manifestation of SSc, contributing to substantial morbidity. We sought to determine whether oesophageal dysmotility patterns by high-resolution oesophageal manometry were associated with distinct SSc clinical phenotypes and different outcomes. Methods: We analysed a cohort of SSc patients with detailed clinical and immunological data. Oesophageal motility was classified using Chicago 4.0 criteria, and baseline characteristics were compared across motility patterns [absent contractility (AC), ineffective oesophageal motility (IEM) and normal motility]. Associations with adverse outcomes (death or lung transplantation) were evaluated using Kaplan–Meier and Cox regression analyses. Results: Our cohort included 201 patients with SSc (84% female, mean age 45 ± 17 years, follow-up 442 person-years). Oesophageal dysmotility patterns were classified as AC in 86 (43%), IEM in 57 (28%) and normal motility in 58 (29%). AC was associated with dcSSc, more severe digital ulcers, gastric vascular ectasia, anti-Ro60 antibodies and a late pattern on nailfold capillaroscopy (P < 0.05), while IEM was linked to limited SSc, anti-centromere antibodies and an early/active nailfold pattern. Multivariate time-to-event analysis identified AC as an independent risk factor for lung transplantation (HR = 7.004, 95%CI: 1.481–33.135, P = 0.014) after adjusting for both interstitial lung disease and male sex, and for SSc-related death (HR = 3.472, 95%CI: 1.071–10.969, P = 0.038) after adjusting for DcSSc and interstitial lung disease. Conclusions: We found that patients with AC and IEM have distinct clinical phenotypes, suggesting they are distinct entities. In patients with SSc, AC is independently associated with worse outcomes. These data suggest that HREM may be useful in risk stratification and outcome predictions in patients with SSc.

It has been postulated that advanced glycation end products (AGEs) and their soluble receptor (sRAGE) may play a relevant role as inducers in the chronic inflammatory pathway in various conditions, among them, in immune-mediated diseases such as systemic lupus erythematosus (SLE). However, previous studies show conflicting results about their association with SLE characteristics and their usefulness as disease biomarkers. We aimed to study the association of specific serum AGEs (pentosidine, Nξ-(carboxymethyl)lysine (CML), Nξ-(carboxyethyl)lysine (CEL)), sRAGE levels and AGEs (specific serum AGEs and skin AGEs) to sRAGE ratios with various disease parameters, in order to clarify their potential as new biomarkers in SLE and to study their relationship with cardiovascular disease (CVD). To this aim, serum pentosidine, CML, CEL and sRAGE were measured via ELISA, and skin AGEs levels were measured by skin autofluorescence. Correlations of pentosidine levels with demographic and clinical data, indexes of activity, accrual damage and patient-reported outcomes were analyzed through multiple linear regression models, while correlations of the rest of the AGEs, sRAGE and AGE to sRAGE ratios (non-normal) were analyzed using both an OLS regression model and a GML. All of the analyses were adjusted for confounders. A total of 119 SLE patients were recruited. Serum AGEs and sRAGEs were significantly associated with SLE activity indexes and/or demographic or disease characteristics: pentosidine with pulmonary manifestations; CML with anti-dsDNA antibodies, IL-6, disease duration and non-Caucasian ethnicities; CEL with anti-dsDNA antibodies, IL-6 and accumulated number of manifestations; and sRAGE with male gender, photosensitivity and being on specific immunosuppressants. These results suggest that the AGE–sRAGE axis may serve as a novel biomarker for managing and prognosticating this disease. Its correlation with certain antibodies, demographics and disease presentations may indicate a distinct clinical phenotype associated with varying levels of AGEs and/or sRAGE. The significance of specific AGE/sRAGE ratios, introduced in this study for the first time, warrants additional investigation in forthcoming research. Our study did not confirm the link between serum AGEs and CVD, which merits further exploration through studies designed for this specific purpose.

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients’ data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.

Objectives: To determine the prevalence of objectively defined gastric dysmotility in SSc and to evaluate its associations with SSc clinical and immunological features and adverse outcomes (SSc-related death and/or lung transplantation). Methods: We conducted a retrospective cohort study. All participants underwent a standardized 4-h solid gastric emptying scintigraphy. Gastric dysmotility was defined as ≥20% gastric retention at 4-h. We examined associations between gastric dysmotility and demographic, clinical and immunologic characteristics of SSc, as well as relevant clinical outcomes. Results: Ninety-four patients were included (mean age 48 ± 12 years; 81% female). Gastric dysmotility was identified in 33 patients (35%). Patients with gastric dysmotility had a higher prevalence of interstitial lung disease (63.6% vs 30.3%, P = 0.033) and absent oesophageal contractility (75.8% vs 45.9%, P < 0.001) compared with those without. Gastric dysmotility was less frequent in patients with ACAs (27.3% vs 55.0%, P = 0.009) but more common in those with anti-U1RNP antibodies (15.6% vs 1.7%, P = 0.011). During follow-up (mean duration 2.8 ± 1.7 years; 260 person-years), 16 patients (17.0%) experienced the composite end point of SSc-related death and/or lung transplantation. In unadjusted Cox regression, gastric dysmotility was strongly associated with adverse outcomes (HR = 6.47, 95% CI: 2.09–20.10, P = 0.001), which remained significant after adjustment for confounders (HR = 4.23, 95% CI: 1.25–14.33, P = 0.020). Conclusions: In SSc, we have confirmed that gastric dysmotility is associated with a distinct clinical and serological phenotype and that it independently predicts serious adverse outcomes. These findings underscore the importance of objective assessment of gastric function and its potential role in risk stratification.

Introduction: Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Objectives: To confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and study their correlation with various disease parameters. Methods: Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients’ data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Correlations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. Results: AGEs levels in SLE patients were significantly higher than in HC (p<0.001). We found statistically significant positive correlation with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL6 and oral ulcers. We also found a negative statistically significant correlation with current positivity of anti-nuclear and anti-Ro60 antibodies. Conclusions: AGEs seem to have a role in LES pathophysiology, becoming a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher AGEs levels.