Th17 cells that produce interleukin (IL)‐17 play a key role in the pathogenesis of autoimmune inflammation. Among the various cytokines that are involved in the IL‐17 pathway, members of the IL‐1β family, including IL‐18, have recently gained attention. In this study, we stimulated synovial fibroblasts with a combination of IL‐17 and IL‐18 and quantified their stromal cell–derived factor‐1 (SDF‐1) production by enzyme‐linked immunosorbent assay and their transcript levels by reverse transcription–polymerase chain reaction. Both IL‐17 and IL‐18 significantly increased the level of SDF‐1, not only individually but also synergistically (P < 0.05). The synergism was effectively suppressed by anti‐IL‐17 and ‐IL‐18 antibodies, and a PI3K inhibitor. To the best of our knowledge, this is the first report of PI3K‐dependent synergism between IL‐18 and IL‐17, and this work adds a novel perspective of the role of IL‐18 in immune regulation. The individual effects of these two cytokines, and their interactions, suggest an interrelationship between the IL‐1 family and IL‐17.
Background:In the diagnosis of primary Sjogren’ syndrome (SS), salivary gland ultrasound is useful tool. Until now, there is no data for ultasonographic changes of major salivary glands over time.Objectives:This study aimed to evaluate the changes in abnormalities of salivary gland ultrasound (SGUS) over time in patients with pSS.Methods:Patients with pSS (n=70) and idiopathic sicca syndrome (n=18) underwent SGUS twice at baseline and 2 years later. The semi-quantitative SGUS score (0-48) was used, which comprises five parameters: parenchymal echogenicity, homogeneity, hypoechoic areas, hyperechogenic reflections, and clearness of posterior borders. The intraglandular power Doppler signal (PDS) was also assessed. The changes of these SGUS variables were compared in patients with pSS and idiopathic sicca syndrome.Results:The median (interquartile range) total SGUS scores at baseline was 27 (14) in patients with and 4 (3) in those with idiopathic sicca syndrome (p<0.001). In the pSS group, the total SGUS scores and the SGUS scores for bilateral parotid glands were significantly increased during median 23.4 month follow-up (p=0.013 andp=0.011, respectively). Homogeneity and hypoechoic areas were the domain to show statistically significant progression of SGUS scores. None of the SGUS scores changed significantly in the patients with idiopathic sicca syndrome. In patients with pSS, baseline and follow-up PDS sum scores of four salivary glands were significant higher in worsening SGUS group (n=13) than no change/improvement SGUS group (n=55/2).Conclusion:The structural abnormalities in major salivary glands assessed using SGUS scores progressed significantly in patients with pSS. In pSS group, 18.6% patients had worsening SGUS scores during 2 years. Intra-glandular hypervascularity was associated with worsening of salivary gland abnormalities.References:[1]Delli K, Dijkstra PU, Stel AJ, Bootsma H, Vissink A, Spijkervet FK. Diagnostic properties of ultrasound of major salivary glands in Sjogren’s syndrome: a meta-analysis. Oral diseases. 2015;21(6):792-800.[2]Jousse-Joulin S, Devauchelle-Pensec V, Cornec D, Marhadour T, Bressollette L, Gestin S, et al. Brief Report: Ultrasonographic Assessment of Salivary Gland Response to Rituximab in Primary Sjogren’s Syndrome. Arthritis & rheumatology (Hoboken, NJ). 2015;67(6):1623-8.[3]Gazeau P, Cornec D, Jousse-Joulin S, Guellec D, Saraux A, Devauchelle-Pensec V. Time-course of ultrasound abnormalities of major salivary glands in suspected Sjogren’s syndrome. Joint, bone, spine: revue du rhumatisme. 2018;85(2):227-32.[4]Lee KA, Lee SH, Kim HR. Diagnostic and predictive evaluation using salivary gland ultrasonography in primary Sjogren’s syndrome. Clinical and experimental rheumatology. 2018;36 Suppl 112(3):165-72.Acknowledgments: :This work was funded by the Konkuk University Medical Center Research Grant 2019.Disclosure of Interests:None declared
BackgroundObjectives:We evaluated nailfold capillaroscopy (NFC) of interstitial pneumonia with autoimmune features (IPAF) and compared it with that of patients with CTD-ILD and idiopathic interstitial pneumonia (IIP).MethodsPatients with newly diagnosed as ILD were evaluated using NFC. Baseline demographic, clinical, serological, and high-resolution CT findings were collected. NFC was semi-quantitatively scored with six domains ranging from 0 to 18. In addition, the overall patterns (scleroderma/non-scleroderma patterns) were determined.ResultsA total of 81 patients (31 with CTD-ILD, 18 with IPAF, and 32 with IIP) were included. The non-specific interstitial pneumonia pattern was the most common ILD pattern in the CTD-ILD and IPAF groups, whereas the usual interstitial pneumonia pattern was the most common in the IIP group. The semi-quantitative score of the CTD-ILD group was higher than that of the IPAF or IIP groups (5.8 vs 4.2 vs 3.0, p < 0.001, respectively). Giant capillaries and haemorrhages were more frequently present in the CTD-ILD and IPAF groups than in the IIP group. A scleroderma pattern was present in 27.8% of the IPAF group, whereas none of the IIP patients showed a scleroderma pattern.ConclusionNFC findings may be useful in classifying patients with ILD into CTD-ILD/IPAF/IIP.Reference[1]Fischer A, Antoniou KM, Brown KK, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 2015;46:976-987.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
BackgroundThe CT syndesmophyte score (CTSS) can evaluate spinal progression more precisely than mSASSS in ankylosing spondylitis (AS); however, it is complex and time consuming.ObjectivesHere, we propose a simplified CTSS (sCTSS) for measuring spinal structural changes in AS.MethodsPatients with AS were recruited from a single tertiary hospital. Baseline and 2-year follow-up whole spine CT images were used to calculate CTSS and sCTSS. The sCTSS used the anterior and posterior vertebral corners, and ranged 0–184. Intraclass correlation coefficients (ICC) were calculated, as well as the smallest detectable changes.ResultsFifty AS patients were included. For reader 1, the mean sCTSS at baseline and 2-year follow-up were 11.7 ± 14.6 and 15.8 ± 16.1, whereas those for reader 2 were 12.0 ± 12.5 and 15.8 ± 15.7, respectively. The ICCs for CTSS at baseline and at 2-year follow-up were 0.97 (95% confidence interval [CI] 0.96–0.99) and 0.98 (0.97–0.99), respectively, and that for changes over the 2 years was 0.48 (95% CI 0.23–0.67). For sCTSS, the ICCs were 0.96 (95% CI 0.92–0.97), 0.97 (95% CI 0.94–0.98), and 0.58 (95% CI 0.36–0.74), respectively. Detection rates for syndesmophyte progression were comparable between CTSS and sCTSS. The detection rate for syndesmophytes on only lateral side was 13.2 and 11.4%, and 11.4 and 15.2% at baseline and 2-year follow-up (reader 1 and 2).ConclusionsCTSS and CTSS showed similar detection rates for syndesmophyte progression. sCTSS may be a reliable method for evaluating spinal structural damage in AS.References[1]de Bruin, F. et al. Development of the CT Syndesmophyte Score (CTSS) in patients with ankylosing spondylitis: data from the SIAS cohort. Ann Rheum Dis 77, 371-377 (2018).[2]de Koning, A. et al. Low-dose CT detects more progression of bone formation in comparison to conventional radiography in patients with ankylosing spondylitis: results from the SIAS cohort. Ann Rheum Dis 77, 293-299 (2018).[3]Tan, S. et al. Spatial distribution of syndesmophytes along the vertebral rim in ankylosing spondylitis: preferential involvement of the posterolateral rim. Ann Rheum Dis 75, 1951-1957 (2016).Acknowledgements:NIL.Disclosure of InterestsNone Declared.
BackgroundSalivary gland ultrasonography (SGUS) is commonly used in primary Sjögren Disease (pSD) as a diagnostic tool [1]. It could also be used to monitor disease activity, but severity of SGUS parenchymal abnormalities in relation to disease duration is not well characterized.ObjectivesTo assess transversally the severity of ultrasound salivary parenchymal abnormalities in relation to pSD duration.MethodsIn this prospective cross-sectional international multicentric study, patients with pSD according to 2002 or 2016 ACR/EULAR classification criteria were included. Parenchymal abnormalities assessed by ultrasound within both parotid and sub-mandibular glands were reported on a standardized form and classified according to the semi-quantitative score of the OMERACT (global score and each item evaluated separately) [2]. Reliability between experts was measured after online training. Demographic, clinical and paraclinical data were also collected and patients were separated into 4 groups according to disease duration from the first buccal dryness symptoms (group A: < 5 years, group B: between 5 and 10 years, group C: between 10 and 20 years, group D: > 20 years of evolution).The association between disease duration groups and SGUS parenchymal abnormalities was quantified in terms of odds ratio and its 95% confidence interval.Results247 patients were consecutively included between May 2019 and February 2022 in 12 international centers. They were 47, 69, 78 and 53 in groups A, B, C and D, respectively. Women represented 94.7% of patients, with a median age of 58 [range 19-89] years old. Oral and ocular dryness were reported by 99.6% and 95.1% of patients, respectively. Salivary flow was abnormal in 74.7% of patients and Schirmer’s test in 82.1%. The focus score was ≥1/4mm2 in 89% of patients. 85% of patients had positive anti-SSA and 59.6% had rheumatoid factor. The median ESSDAI score was 3 [0-48]. Considering for each patient the gland with the highest US OMERACT score, there was a global significant association between disease duration and OMERACT score (OR for 5 years duration: 1.23 [IC95% 1.04; 1.47], p=0.02). When comparing groups A+B versus C+D on the OMERACT score, the OR was 1.95 [IC95% 1.10; 3.46], p=0.02, while no significant difference was found when comparing group A versus B+C+D. Considering each item of the OMERACT score, there was not any statistical difference between the 4 groups in relation to the proportion of an/hypoechoic areas in the gland nor homogeneity or posterior border visibility. The only statistical difference between groups was found regarding the proportion of hyperechoic bands (p = 0.0009). When comparing group A versus B+C+D on this item, the OR was 2.55 [95%CI 1.30-5.01], p=0.006).ConclusionThis large international transversal study in patients with pSD found a positive association between global SGUS lesions evaluated by the OMERACT score and disease duration, with a significant difference only observed in the proportion of hyperechoic bands, when considering separately each item of the score. This may suggest a progressive fibro-adipous evolution of the gland across disease duration. The presence of diffuse hyperechoic bands (grade 3 in the OMERACT scoring system), corresponding to a higher disease duration group, could be useful in the future to stratify patients in clinical trials and to interpret SGUS modifications after treatment.References[1]Jousse-Joulin S, Gatineau F, Baldini C, Baer A, Barone F, Bootsma H, et al. Weight of salivary gland ultrasonography compared to other items of the 2016 ACR/EULAR classification criteria for Primary Sjögren’s syndrome. J Intern Med. 2020 Feb;287(2):180–8.[2]Jousse-Joulin S, D’Agostino MA, Nicolas C, Naredo E, Ohrndorf S, Backhaus M, et al. Video clip assessment of a salivary gland ultrasound scoring system in Sjögren’s syndrome using consensual definitions: an OMERACT ultrasound working group reliability exercise. Ann Rheum Dis. 2019 Jul;78(7):967–73.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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