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| 2. |
- Rusakiewicz, Sylvie, et al.
(författare)
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NCR3/NKp30 contributes to pathogenesis in primary Sjogren's syndrome.
- 2013
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Ingår i: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 5:195
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Tidskriftsartikel (refereegranskat)abstract
- Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by a lymphocytic exocrinopathy. However, patients often have evidence of systemic autoimmunity, and they are at markedly increased risk for the development of non- Hodgkin's lymphoma. Similar to other autoimmune disorders, a strong interferon (IFN) signature is present among subsets of pSS patients, although the precise etiology remains uncertain. NCR3/NKp30 is a natural killer (NK)-specific activating receptor regulating the cross talk between NK and dendritic cells and type II IFN secretion. We performed a case-control study of genetic polymorphisms of the NCR3/NKp30 gene and found that rs11575837 (G>A) residing in the promoter was associated with reduced gene transcription and function as well as protection to pSS. We also demonstrated that circulating levels of NCR3/NKp30 were significantly increased among pSS patients compared with controls and correlated with higher NCR3/NKp30 but not CD16-dependent IFN-γ secretion by NK cells. Excess accumulation of NK cells in minor salivary glands correlated with the severity of the exocrinopathy. B7H6, the ligand of NKp30, was expressed by salivary epithelial cells. These findings suggest that NK cells may promote an NKp30-dependent inflammatory state in salivary glands and that blockade of the B7H6/NKp30 axis could be clinically relevant in pSS.
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| 3. |
- Seror, Raphaele, et al.
(författare)
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EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren's syndrome
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:6, s. 968-972
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To develop a score for assessment of patients' symptoms in primary Sjogren's syndrome (SS): the EULAR SS Patient Reported Index (ESSPRI). Methods Dryness, pain, somatic and mental fatigue were identified as the main symptoms of patients with primary SS, in studies developing the Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptoms Inventory (SSI). It was suspected that a single 0-10 numerical scale for each domain was sufficient to assess these symptoms. These four scales were gathered to form the ESSPRI. 230 patients, from 12 countries completed the ESSPRI, SSI and PROFAD questionnaires and a 0-10 patient global assessment (PGA). Correlations between each symptom and PGA were obtained. Multiple regression modelling, using PGA as 'gold standard' was used to select domains and estimate their weights. Results PGA had good correlation with dryness, limb pain, fatigue and mental fatigue (r=0.49-0.59, all p<0.0001), but correlated less well with individual dryness features. In multivariate analysis, dryness, limb pain and fatigue, but not mental fatigue, were significantly associated with PGA; weights derived from the regression were identical for these three domains. Thus, ESSPRI was redefined as the mean of the three scales: dryness, limb pain and fatigue. Lastly, ESSPRI significantly correlated with PGA (r=0.70), PROFAD (r=0.73) and SSI (r=0.66). Conclusion ESSPRI is a very simple index designed to measure patients' symptoms in primary SS. It has good construct validity and is well correlated with SSI and PROFAD. ESSPRI should now be validated for use as an outcome measure in clinical trials.
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| 4. |
- Seror, Raphaele, et al.
(författare)
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Validation of EULAR primary Sjogren's syndrome disease activity (ESSDAI) and patient indexes (ESSPRI)
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 74:5, s. 859-866
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To validate the two recently developed disease activity indexes for assessment of primary Sjogren's syndrome (SS): the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI). Methods A prospective international 6-month duration validation study was conducted in 15 countries. At each visit, physicians completed ESSDAI, SS disease activity index (SSDAI), Sjogren's Systemic Clinical Activity Index (SCAI) and physician global assessment (PhGA); and patients completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and Discomfort (PROFAD) and patient global assessment (PGA). Psychometric properties (construct validity, responsiveness and reliability) were evaluated and compared between scores. Results Of the 395 patients included, 145 (37%) and 251 (64%) had currently active or current or past systemic manifestations, respectively. EULAR scores had higher correlation with the gold standard than other scores (ESSDAI with PhGA: r= 0.59; ESSRPI with PGA: r= 0.70). Correlations between patient and systemic scores were very low (ranging from 0.07 to 0.29). All systemic scores had similar large responsiveness in improved patients. Responsiveness of patient scores was low but was significantly higher for ESSPRI compared with SSI and PROFAD. Reliability was very good for all scores. Conclusions ESSDAI and ESSPRI had good construct validity. All scores were reliable. Systemic scores had a large sensitivity to change in patients whose disease activity improves. Patient scores had a small sensitivity to change, however, significantly better for ESSPRI. Systemic and patient scores poorly correlated, suggesting that they are 2 complementary components that should be both evaluated, but separately.
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| 6. |
- Seror, Raphaele, et al.
(författare)
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Accurate Detection of Changes in Disease Activity in Primary Sjogren's Syndrome by the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index
- 2010
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 62:4, s. 551-558
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To assess and compare the sensitivity to change of the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) with that of other primary Sjogren's syndrome (SS) disease activity indexes. Methods. We abstracted 96 patient profiles, including data on 3 successive visits (visits 1-3), from the medical charts of patients with primary SS. Patient profiles were scored with the ESSDAI, SS Disease Activity Index (SSDAI), and Sjogren's Systemic Clinical Activity Index (SCAI). Thirty-nine experts assessed 5 profiles for whether disease activity had improved, worsened, or remained stable at visits 2 and 3. Results. For improved patients, the standardized response means (SRMs) for all scores did not differ, and ranged from -1.08 to -1.38 between visits 1 and 2 and from -0.50 to -0.76 between visits 2 and 3. For patients with worsened activity, the SRMs between visits 1 and 2 and between visits 2 and 3 were +0.46 and +1.10 for the ESSDAI, -0.03 and +0.79 for the SSDAI, and +0.17 and +1.02 for the SCAI, respectively. For patients with stable activity, the SRMs between visits 1 and 2 and between visits 2 and 3 were 0.00 and -0.13 for the ESSDAI, -0.44 and -0.11 for the SSDAI, and -0.36 and +0.34 for the SCAI, respectively. Conclusion. For patients with improved activity, the 3 disease activity indexes showed similar, large sensitivity to change. However, the ESSDAI seemed to detect changes in activity more accurately than other disease activity indexes. Notably, for patients with stable activity, the ESSDAI did not show erroneous improvement.
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| 7. |
- Seror, Raphaele, et al.
(författare)
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EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome
- 2010
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:6, s. 1103-1109
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Tidskriftsartikel (refereegranskat)abstract
- Objective To develop a disease activity index for patients with primary Sjogren's syndrome (SS): the European League Against Rheumatism (EULAR) Sjogren's syndrome disease activity index (ESSDAI). Methods Thirty-nine SS experts participated in an international collaboration, promoted by EULAR, to develop the ESSDAI. Experts identified 12 organ-specific 'domains' contributing to disease activity. For each domain, features of disease activity were classified in three or four levels according to their severity. Data abstracted from 96 patients with systemic complications of primary SS were used to generate 702 realistic vignettes for which all possible systemic complications were represented. Using the 0-10 physician global assessment (PhGA) scale, each expert scored the disease activity of five patient profiles and 20 realistic vignettes. Multiple regression modelling, with PhGA used as the dependent variable, was used to estimate the weight of each domain. Results All 12 domains were significantly associated with disease activity in the multivariate model, domain weights ranged from 1 to 6. The ESSDAI scores varied from 2 to 47 and were significantly correlated with PhGA for both real patient profiles and realistic vignettes (r = 0.61 and r = 0.58, respectively, p < 0.001). Compared with 57 (59.4%) of the real patient profiles, 468 (66.7%) of the realistic vignettes were considered likely or very likely to be true. Conclusion The ESSDAI is a clinical index designed to measure disease activity in patients with primary SS. Once validated, such a standardised evaluation of primary SS should facilitate clinical research and be helpful as an outcome measure in clinical trials.
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| 8. |
- Seror, Raphaele, et al.
(författare)
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Outcome measures for primary Sjogren's syndrome
- 2012
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 39:1-2, s. 97-102
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Forskningsöversikt (refereegranskat)abstract
- Lymphocytic infiltration of different exocrine and non-exocrine epithelia is the pathological hallmark of primary Sjogren's syndrome, whereas involvement of salivary and lachrymal glands with the clinical counterpart of dry eye and dry mouth are the predominant features of the disease, together with fatigue and musculoskeletal pain. In addition, systemic manifestations, like arthritis, skin vasculitis, peripheral neuropathy, glomerulonephritis, may also be present in a consistent number of patients. As result, clinical features in SS can be divided into two facets: the benign subjective but disabling manifestations such as dryness, pain and fatigue, and the systemic manifestations. In the past decades, a core set of domains, which included sicca symptoms, objective measurements of tear and saliva production, fatigue, quality of life, disease activity and damage was indicated as essential for outcome assessment in this disorder. Afterwards, great efforts have been made to develop valid tools for the assessment of different domains. Specific questionnaires such as the Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptoms Inventory (SSI) have been proposed as dedicated tools for the evaluation of patients symptoms, whereas different composite indexes have been suggested for the assessment of disease activity and damage. Some of these preliminary studies served as bases of an international project supported by EULAR, aimed at developing two consensus disease activity indexes: the EULAR Sjogren's Syndrome Patients Reported Index (ESSPRI), and the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI), a systemic activity index to assess systemic manifestations. A detailed and critical review of all these indexes is provided in this article. Both EULAR indexes showed, in recent studies, to be feasible, valid, and reliable instruments. After their final validation, which is currently in process, they could be used as consensus outcome criteria in therapeutic trials and in clinical practice. (C) 2012 Published by Elsevier Ltd.
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| 9. |
- Seror, Raphaèle, et al.
(författare)
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Outcome measures for primary Sjögren's syndrome: A comprehensive review.
- 2014
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 51:Jan 7, s. 51-56
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Forskningsöversikt (refereegranskat)abstract
- Lymphocytic infiltration of different exocrine and non-exocrine epithelia is the pathological hallmark of primary Sjögren's syndrome, whereas involvement of salivary and lachrymal glands with the clinical counterpart of dry eye and dry mouth are the predominant features of the disease, together with fatigue and musculoskeletal pain. In addition, systemic manifestations, like arthritis, skin vasculitis, peripheral neuropathy, glomerulonephritis, may also be present in a consistent number of patients. As result, clinical features in SS can be divided into two facets: the benign subjective but disabling manifestations such as dryness, pain and fatigue, and the systemic manifestations. In the past decades, great efforts have been made to develop valid tools for the assessment of these both facets. Disease specific questionnaires such as Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptom Inventory (SSI) have been proposed for evaluation of patients' symptoms, whereas different composite indexes have been suggested for the assessment of systemic disease activity. After that, an international project supported by EULAR, emerged to develop consensus disease activity indexes: the EULAR Sjögren's Syndrome Patients Reported Index (ESSPRI), and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), a systemic activity index to assess systemic manifestations. Both EULAR indexes have been developed in an international collaboration to be consensual. Both indices have now been validated in a large independent international cohort. They both have been shown to be feasible, valid and reliable instruments. Also, we have found that these two scores did not correlate, suggesting that these two indexes assess two different disease components that poorly overlap, but were complementary. The sensitivity to change of both scores has been assessed, they are both able to detect change, however, ESSDAI score, like other systemic score, is more sensitive to change than ESSPRI and other patient scores. Current work is ongoing to define disease activity levels and clinically important changes for defining significant clinical improvement with the systemic score ESSDAI, and ESSPRI. We hope that this increased knowledge on the way to assess patients with primary SS, along with the emergence of new targeted therapy, will put a great input in the improvement of conduction of clinical trials in pSS.
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| 10. |
- Vitali, Claudio, et al.
(författare)
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Classification criteria for Sjogren's syndrome: we actually need to definitively resolve the long debate on the issue
- 2013
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 72:4, s. 476-478
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Tidskriftsartikel (refereegranskat)abstract
- A new approach for the classification of patients with Sjogren's syndrome (SS) has been recently proposed. Although these new criteria substantially differ from the American European Consensus Group criteria, which have represented the gold standard for the last decade, when compared with each other the two sets show a high statistical degree of agreement. However, the fact that two different criteria to classify patient with SS could be available may introduce some additional difficulties in the scientific communication, making cohorts of patients selected by using different methods less than completely equivalent, and the results of epidemiological studies and therapeutic trials not entirely comparable. Consequently, to reach a consensus agreement on universally accepted classification criteria for SS seems to be a very desirable objective.
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