Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren's syndrome

Labial salivary gland (LSG) biopsy is used in the classification of primary Sjögren's syndrome (PSS) and in patient stratification in clinical trials. It may also function as a biomarker. The acquisition of tissue and histological interpretation is variable and needs to be standardised for use in clinical trials. A modified European League Against Rheumatism consensus guideline development strategy was used. The steering committee of the ad hoc working group identified key outstanding points of variability in LSG acquisition and analysis. A 2-day workshop was held to develop consensus where possible and identify points where further discussion/data was needed. These points were reviewed by a subgroup of experts on PSS histopathology and then circulated via an online survey to 50 stakeholder experts consisting of rheumatologists, histopathologists and oral medicine specialists, to assess level of agreement (0–10 scale) and comments. Criteria for agreement were a mean score ≥6/10 and 75% of respondents scoring ≥6/10. Thirty-nine (78%) experts responded and 16 points met criteria for agreement. These points are focused on tissue requirements, identification of the characteristic focal lymphocytic sialadenitis, calculation of the focus score, identification of germinal centres, assessment of the area of leucocyte infiltration, reporting standards and use of prestudy samples for clinical trials. We provide standardised consensus guidance for the use of labial salivary gland histopathology in the classification of PSS and in clinical trials and identify areas where further research is required to achieve evidence-based consensus

Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjögren's syndrome

OBJECTIVE To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. METHODS The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. RESULTS The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P 65 years, P < 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P < 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P < 0.001). CONCLUSION The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis

Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients: a cross-sectional study from the Big Data Sjögren Project Consortium

OBJECTIVES: To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed. RESULTS: We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69). CONCLUSIONS: This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis

Milieu en sociale (on)gelijkheid in Nederland - Een casusonderzoek naar de verdeling van milieukwaliteit in de regio Rijnmond

As a part of a broader investigation on environmental inequity in the Netherlands, an exploratory case study on the socio-economic distribution on (perceived) environmental quality was carried out in the Rijnmond (industrial and urbanised) region in the western part of the Netherlands. Disparities in local environmental quality with respect to noise, air pollution, availability of public green areas, safety risks, and presence of waste disposal sites, were analysed separately and accumulatively across income levels making use of postal codes. Inhabitants' perception of environmental quality with respect to spatial and income differences was also ascertained and analysed. Recent, available national and regional databases and literature were used for the analyses. Disparities in local environmental quality were found to be linked to income level, especially for air pollution and the availability of public green areas. In addition, accumulation of environmental 'goods' (high-quality environmental conditions) were found more often in high-income than in low-income areas. Inhabitants of Rotterdam also mentioned littering and dog mess to be the greatest environmental problem. All income categories experienced annoyance, but from different, often area-specific sources. Considering these results, policy-makers are advised to take the effects of their policy on different income categories into account.Als onderdeel van een breder onderzoek naar milieu en sociale ongelijkheid in Nederland is een verkennend casusonderzoek uitgevoerd naar de sociaal-economische verdeling van (ervaren) milieukwaliteit in de regio Rijnmond. Verschillen in milieukwaliteit tussen postcodegebieden met een verschillend inkomensniveau zijn geanalyseerd voor geluid, luchtverontreiniging, beschikbaarheid van groen, veiligheidsrisico's en aanwezigheid van afvalverwerkingsbedrijven, zowel voor de afzonderlijke aspecten als gecumuleerd. Verder is ervaren milieukwaliteit van bewoners vastgesteld en geanalyseerd op ruimtelijke en inkomensverschillen en de relatie van beleving met 'objectieve' milieukwaliteit. Dit is gedaan op basis van recente literatuur en bestaande nationale en regionale gegevensbestanden. Er bleken verschillen in lokale milieukwaliteit te bestaan tussen postcodegebieden met een verschillend inkomensniveau, met name voor luchtverontreiniging en beschikbaarheid van groen. Ook bleek stapeling van positieve milieu-aspecten vaker voor te komen in hogere inkomensgebieden dan in lagere inkomensgebieden. Daarnaast noemden Rotterdammers vuil op straat en hondenpoep als grootste milieuproblemen. Alle inkomenscategorieen ervoeren hinder, maar van verschillende, vaak locatiespecifieke bronnen. Gezien deze resultaten is het voor beleidsmakers van belang in hun beleid aandacht te besteden welke uitwerking deze heeft voor verschillende inkomensgroepen

Milieu en sociale (on)gelijkheid in Nederland - Een casusonderzoek naar de verdeling van milieukwaliteit in de regio Rijnmond

Dit rapport bevat een Erratum op pagina 2Als onderdeel van een breder onderzoek naar milieu en sociale ongelijkheid in Nederland is een verkennend casusonderzoek uitgevoerd naar de sociaal-economische verdeling van (ervaren) milieukwaliteit in de regio Rijnmond. Verschillen in milieukwaliteit tussen postcodegebieden met een verschillend inkomensniveau zijn geanalyseerd voor geluid, luchtverontreiniging, beschikbaarheid van groen, veiligheidsrisico's en aanwezigheid van afvalverwerkingsbedrijven, zowel voor de afzonderlijke aspecten als gecumuleerd. Verder is ervaren milieukwaliteit van bewoners vastgesteld en geanalyseerd op ruimtelijke en inkomensverschillen en de relatie van beleving met 'objectieve' milieukwaliteit. Dit is gedaan op basis van recente literatuur en bestaande nationale en regionale gegevensbestanden. Er bleken verschillen in lokale milieukwaliteit te bestaan tussen postcodegebieden met een verschillend inkomensniveau, met name voor luchtverontreiniging en beschikbaarheid van groen. Ook bleek stapeling van positieve milieu-aspecten vaker voor te komen in hogere inkomensgebieden dan in lagere inkomensgebieden. Daarnaast noemden Rotterdammers vuil op straat en hondenpoep als grootste milieuproblemen. Alle inkomenscategorieen ervoeren hinder, maar van verschillende, vaak locatiespecifieke bronnen. Gezien deze resultaten is het voor beleidsmakers van belang in hun beleid aandacht te besteden welke uitwerking deze heeft voor verschillende inkomensgroepen.As a part of a broader investigation on environmental inequity in the Netherlands, an exploratory case study on the socio-economic distribution on (perceived) environmental quality was carried out in the Rijnmond (industrial and urbanised) region in the western part of the Netherlands. Disparities in local environmental quality with respect to noise, air pollution, availability of public green areas, safety risks, and presence of waste disposal sites, were analysed separately and accumulatively across income levels making use of postal codes. Inhabitants' perception of environmental quality with respect to spatial and income differences was also ascertained and analysed. Recent, available national and regional databases and literature were used for the analyses. Disparities in local environmental quality were found to be linked to income level, especially for air pollution and the availability of public green areas. In addition, accumulation of environmental 'goods' (high-quality environmental conditions) were found more often in high-income than in low-income areas. Inhabitants of Rotterdam also mentioned littering and dog mess to be the greatest environmental problem. All income categories experienced annoyance, but from different, often area-specific sources. Considering these results, policy-makers are advised to take the effects of their policy on different income categories into account.RIVM VROM-DGM-LM

Increased interleukin (IL)-7R alpha expression in salivary glands of patients with primary Sjogren's syndrome is restricted to T cells and correlates with IL-7 expression, lymphocyte numbers and activity

Objective To identify interleukin (IL)-7R alpha expression in the labial salivary gland (LSG) of patients with primary Sjogren's syndrome (pSS) and non-Sjogren's syndrome sicca (nSS-sicca) and to study its correlation with glandular inflammation and IL-7 expression. Methods The presence of infiltrating immune cells and IL-7R alpha cells in inflamed LSG of patients with pSS (n=12) and nSS-sicca controls (n=7) was studied by immunohistochemistry and fluorescence activated cell sorting analysis upon tissue digestion (n=15 and n=13, respectively). Additionally, the correlations of IL-7R alpha cells with hallmark disease parameters of pSS, major infiltrating inflammatory cells and IL-7 were assessed. Results In the LSG of patients with pSS increased numbers of IL-7R alpha cells were found as compared with nSS-sicca patients. IL7R alpha cells strongly correlated with the lymphocytic focus score, IL-7 expression, the decrease in percentage of IgA plasma cells and numbers of CD3 T cells, CD20 B cells, and CD1a and CD208 myeloid dendritic cells. Analysis of isolated cells from the LSG demonstrated strongly increased percentages of IL-7R alpha CD3 T cells in pSS as compared with nSS, showing abun Conclusions This study shows the presence of increased IL-7R alpha T cells in the LSG of patients with pSS and their association with the severity of sialadenitis, disease parameters and IL-7 expression. Considering the immunostimulatory ability of IL-7R alpha T cells and IL-7, this suggests that IL-7(R)-dependent T cell-driven immune activation plays an important role in inflammation in pSS