Objectives Cardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary Sjögren’s syndrome (pSS). Correlations with clinical factors such as organ involvement (OI) or disease activity were analysed and oxLDL antibodies (oxLDL ab) were measured as potential biomarkers of vascular damage. Methods Patients with pSS were consecutively included from the rheumatology outpatient clinic. Age- and sex-matched controls were recruited (2:1 ratio). Data collection was performed by a standardised questionnaire and Doppler ultrasound to evaluate the plaque extent and carotid intima-media thickness (cIMT). Propensity score matching included all cardiovascular risk (CVR) factors and corresponding laboratory markers. Results Data were available for 299 participants (199 pSS/100 controls), aged 59.4 years (50.6–65.0), 19.1% male. After matching, the pSS cohort had greater cIMT (p<0.001) and plaque extent (OR=1.82; 95% CI 1.14 to 2.95). Subgroup analyses of patients with pSS revealed that OI was associated with increased cIMT (p=0.025) and increased plaque occurrence compared with patients without OI (OR=1.74; 95% CI 1.02 to 3.01). OxLDL ab tended to be lower in patients with plaque (p=0.052). Correlations of higher Oxidized Low Density Lipoprotein (oxLDL) ab with EULAR Sjögren’s Syndrome Disease Activity Index (p<0.001) and anti–Sjögren's-syndrome-related antigen A autoantibodies (SSA/Ro antibodies) (p=0.026) were observed. Conclusions Subclinical atherosclerosis occurs earlier and more severely in patients with pSS. The difference in cIMT between pSS and controls seems mainly driven by patients with OI, suggesting that this subgroup is particularly at risk. OxLDL ab might protect against atherosclerotic progression in patients with pSS. CVR stratification and preventive medications such as Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors should be discussed and further longitudinal studies are needed.

Background MicroRNAs (miRNAs) can regulate gene expression, controlling numerous cellular processes. Dysregulation of miRNA function is linked to various diseases, making them attractive diagnostic and therapeutic targets. Examples include hsa-miR-92a-3p, hsa-miR-126-3p, hsa-miR-143-3p, hsa-miR-145-5p and hsa-miR-204-5p, which are associated with endothelial function. Their prevalence in Sjögren’s disease (SjD) is unknown. We assessed the prevalence of these miRNAs in serum of patients with SjD, correlating levels with cardiovascular risk factors and carotid intima-media thickness (cIMT) to evaluate their utility in risk stratification. Methods 199 patients with SjD and 100 age and sex-matched healthy controls (HC) were included in the study. Five different miRNAs (hsa-miR-92a-3p; hsa-miR-126-3p; hsa-miR143-3p; hsa-miR-145-5p; hsa-miR-204-5p) were analysed by quantitative real-time PCR. The miRNA results were compared with known clinical and disease-related parameters. Results Four miRNAs showed significantly different expressions compared with HC. MiR-92a-3p was upregulated (p=0.025) and miR-126-3p (p=0.044), miR-143-3p (p=0.006) and miR-204-5p (p=0.009) downregulated in SjD compared with HC. The comparison between HC and SjD with/without organ involvement revealed descriptively increased miR-92a-3p levels in patients with SjD with organ involvement (p=0.087). Furthermore, miR-92a-3p levels correlated positively with cIMT as an expression of subclinical atherosclerosis (r=0.148, p=0.04). Conclusion In conclusion, patients with SjD demonstrated differences in their expression of miRNAs linked to regulation of endothelial function. Reduction of specific miRNAs was associated with increased cardiovascular risk, suggesting a potentially protective role for these miRNAs. Furthermore, miR-92a-3p could be helpful for molecular detection of early-stage atherosclerosis and increased cardiovascular risk in SjD.

Zusammenfassung: Mit einer Prävalenz von circa 1:100 bis 1:400 ist das Sjögren-Syndrom die häufigste Kollagenose und betrifft hauptsächlich Frauen. Bei der Erkrankung steht die Destruktion der exokrinen Drüsen im Vordergrund und führt so regelhaft zur Sicca-Symptomatik. In über 50% der Fälle kommt es auch zu extraglandulären Manifestationen. Insbesondere Fatigue und Arthralgien aber auch verschiedene systemische Organmanifestationen wie Polyneuropathien oder interstitielle Lungenerkrankungen können auftreten. PatientInnen mit bestimmten Risikofaktoren haben eine Wahrscheinlichkeit von fünf Prozent ein Lymphom zu entwickeln. Die Diagnostik orientiert sich an den aktuellen ACR/EULAR-Klassifikationskriterien, der Speicheldrüsensonographie, sowie diversen Biomarkern, insbesondere den Antikörpern gegen SSA/Ro, in Verbindung mit der klinischen Symptomatik. Es gibt bislang keine zugelassene systemische immunsuppressive Therapie. Die European League against rheumatism (EULAR) hat Therapieempfehlungen veröffentlicht, die sich an den Empfehlungen für die Therapie des Systemischen Lupus Erythematodes orientieren und je nach klinischer Ausprägung und Manifestation variieren. Verschiedene, durchaus vielversprechende Studien zu unterschiedlichen therapeutischen Ansätzen werden aktuell durchgeführt.

Zusammenfassung: Obwohl die Sjögren-Erkrankung (SjD) die häufigste Kollagenose ist, verfügen wir bislang über keine zugelassenen Medikamente für die systemische Behandlung. Viele DMARDs („disease-modifying antirheumatic drugs“) und Biologika konnten in Studien keine ausreichende Wirksamkeit zeigen. Gründe hierfür sind u. a. komplexe immunologische Pathomechanismen sowie eine hohe klinische und immunologische Heterogenität der Patient:innen. In den letzten Jahren kam es jedoch zu deutlichen Fortschritten: Erstmals berichteten Phase-3-Studien 2025 (Ianalumab und Telitacicept) positive Ergebnisse. Grundlage der aktuellen Therapieempfehlungen sind v. a. die Leitlinien der European Alliance of Associations for Rheumatology (EULAR, 2020) und die Empfehlungen der British Society for Rheumatology (BSR, 2024). Die Therapie orientiert sich aktuell primär an den führenden Symptomen. Basis ist die konsequente Behandlung der Sicca-Symptomatik (Augen- und Mundpflege, ggf. Pilocarpin). Extraglanduläre Manifestationen werden überwiegend off-label mit konventionellen DMARDs behandelt; bei schweren Verläufen kommen Rituximab, seltener Cyclophosphamid oder intravenöse Immunoglobuline (IVIG) zum Einsatz. Neue Therapieansätze zeigen erstmals eine anhaltende Reduktion der Krankheitsaktivität: Besonders B‑Zell-gerichtete Therapien (Ianalumab, Telitacicept), FcRn-Inhibitoren (Nipocalimab, Efgartigimod), CD40/CD40L-Blockade, Kinase-Inhibitoren und weitere immunmodulatorische Strategien erzielten in kontrollierten Studien signifikante Verbesserungen im ESSDAI (EULAR Sjögren’s Syndrome Disease Activity Index) und teils im ESSPRI (EULAR Sjögren’s Syndrome Patient-Reported Index) bei akzeptablem Sicherheitsprofil. Während Basismaßnahmen unverzichtbar bleiben, markieren neue zielgerichtete Therapien einen Wendepunkt in der SjD-Behandlung. Insbesondere B‑Zell- und FcRn-gerichtete Ansätze eröffnen erstmals die Perspektive auf evidenzbasierte systemische Therapien über die reine Symptomkontrolle hinaus.

Background/Objectives: This study investigates the macular microvasculature in a large cohort of primary Sjögren’s disease (SjD) patients using optical coherence tomography angiography (OCTA), focusing on how disease duration, activity, and hydroxychloroquine (HCQ) treatment influence retinal microcirculation. Methods: A total of 106 eyes (53 SjD patients) and 70 eyes (35 age- and gender-matched healthy controls (HCs)) were examined. The vessel area density (VAD, %) and foveal avascular zone (FAZ, mm2) were measured in three retinal layers: Superficial Vascular Plexus (SVP), Intermediate Capillary Plexus (ICP), and Deep Capillary Plexus (DCP), respectively, in three peri-macular circular sectors (c1, c2, c3) each. Results: The VAD was significantly lower in c1 of the DCP in SjD compared to HCs (29.14 ± 7.07 vs. 31.78 ± 9.55, p = 0.038). The FAZ was significantly larger in SjD in both SVP (0.41 ± 0.13 vs. 0.34, 0.11, p < 0.001; Cohen’s |d| = 0.55) and DCP (0.45 ± 0.15 vs. 0.4 ± 0.14, p = 0.014; Cohen’s |d| ± 0.38). Significant correlations were observed between the FAZ size and reductions in the VAD in the SVP and DCP (p = 0.010, Cohen’s |d| = 0.2; p < 0.001, Cohen’s |d| ± 0.26) and across all layers combined (p = 0.019, Cohen’s |d| = −0.18). Conclusions: There was a negative correlation between the VAD in the DCP and disease duration (ρ = −0.28, p = 0.040). No significant correlation was identified between the duration of HCQ intake and the VAD or FAZ. Our findings indicate microvascular alterations in the DCP of SjD, characterized by a reduced VAD and an enlarged FAZ, which may be attributable to inflammatory or arteriosclerotic factors. OCTA may prove to be a valuable tool for the stratification of vascular risk in SjD.