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Increased circulating levels and salivary gland expression of interleukin-18 in patients with Sjögren's syndrome: relationship with autoantibody production and lymphoid organization of the periductal inflammatory infiltrate
IL-18, an immunoregulatory and proinflammatory cytokine, has been shown to play an important pathogenic role in Th1-driven autoimmune disorders. In this study, we evaluated the circulating levels and salivary-gland expression of IL-18 in patients with Sjögren's syndrome (SS), a mainly Th1-mediated disease. IL-18 serum levels were measured by ELISA in 37 patients with primary SS, 42 with rheumatoid arthritis, and 21 normal controls. We demonstrated high IL-18 serum levels in SS, similar to those in rheumatoid arthritis patients and significantly higher than in controls (P < 0.01). In addition, IL-18 serum concentrations were significantly higher in anti-SSA/Ro+ and anti-SSB/La+ than in anti-SSA/Ro- and anti-SSB/La- SS patients (respectively, P = 0.01, P < 0.01). Serum IL-18 correlated strongly with anti-SSA/Ro (P = 0.004) and anti-SSB/La (P = 0.01) titers. Salivary gland IL-18 expression was investigated by single/double immunohistochemistry in 13 patients with primary SS and in 10 with chronic sialoadenitis, used as controls. The expression of IL-18 was also examined in periductal inflammatory foci in relation to the acquisition of features of secondary lymphoid organs such as T–B compartmentalization, formation of follicular dendritic cell networks, and presence of germinal-center-like structures. IL-18 expression in SS salivary glands was detected in 28 of 32 periductal foci of mononuclear cells (87.5%), while no IL-18 production by infiltrating cells was detected in patients with chronic sialoadenitis. Within the inflammatory foci, IL-18 immunoreactivity co-localized almost exclusively with CD68+ macrophages. In addition, IL-18 was found in 15 of 19 foci (78.9%) with no evidence of T–B cell compartmentalization (nonsegregated) but in 100% of the segregated aggregates, both in T- and B-cell-rich areas. Strikingly, IL-18 was strongly expressed by CD68+ tingible body macrophages in germinal-centre-like structures both in SS salivary glands and in normal lymph nodes. IL-18 expression was observed in the ducts of all SS biopsies but in only 4 of 10 patients with nonspecific chronic sialoadenitis (P < 0.01). This study provides the first evidence of increased circulating levels and salivary gland expression of IL-18 in SS, suggesting an important contribution of this cytokine to the modulation of immune inflammatory pathways in this condition
Cardiovascular disease risk burden in primary Sjögren's syndrome: results of a population-based multicentre cohort study.
Cardiovascular disease risk burden in primary Sjögren's syndrome: results of a population-based multicentre cohort study.
Bartoloni E1, Baldini C, Schillaci G, Quartuccio L, Priori R, Carubbi F, Bini V, Alunno A, Bombardieri S, De Vita S, Valesini G, Giacomelli R, Gerli R.
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Abstract
OBJECTIVE:
Systemic autoimmune diseases, in particular systemic lupus erythematosus and rheumatoid arthritis, are characterized by a high risk of premature cardiovascular (CV) events. Disease-related characteristics and traditional CV disease risk factors may contribute to atherosclerotic damage. However, there are limited data on the risk of overt CV events in primary Sjögren's syndrome (pSS).
METHODS:
We retrospectively analysed a cohort of patients with 1343 pSS. Disease-related clinical and laboratory data, traditional CV disease risk factors and overt CV events were recorded. Prevalence of traditional CV disease risk factors and of major CV events was compared between a subgroup of 788 female patients with pSS aged from 35 to 74 years and 4774 age-matched healthy women.
RESULTS:
Hypertension and hypercholesterolaemia were more prevalent, whereas smoking, obesity and diabetes mellitus were less prevalent, in women with pSS than in control subjects. Cerebrovascular events (2.5% vs. 1.4%, P = 0.005) and myocardial infarction (MI) (1.0% vs. 0.4%, P = 0.002) were more common in patients with pSS. In the whole population, central nervous system involvement (odds ratio (OR) 5.6, 95% confidence interval (CI) 1.35-23.7, P = 0.02) and use of immunosuppressive therapy (OR 1.9, 95% CI 1.04-3.70, P = 0.04) were associated with a higher risk of CV events. Patients with leucopenia had a higher risk of angina (P = 0.01).
CONCLUSIONS:
pSS is associated with an increased risk of cerebrovascular events and MI. Disease-related clinical and immunological markers may have a role in promoting CV events.
© 2015 The Association for the Publication of the Journal of Internal Medicine.
KEYWORDS:
Sjögren's syndrome; atherosclerosis; autoimmune disease; cardiovascular disease risk factor
Mulini a scanalatura e mulini a tramoggia: definizione e sviluppo della tecnologia molitoria durante il I millennio a.C.
Undifferentiated connective tissue diseases (UCTD): a review of the literature and a proposal for preliminary classification criteria.
Vicini d'Europa. L'attivazione degli abitanti per il benessere urbano
L'articolo ricostruisce gli obiettivi, il percorso e gli esiti del programma Interreg III "Vicini d'Europa" che ha visto quattro città - Belfast, Bruxelles, Lione, Milano - impegnate a declinare il tema del valore che la partecipazione degli abitanti può assumere nel miglioramento della qualità della vita nei propri contesti urbani, organizzando momenti di confronto e di lavoro fra abitanti impegnati in alcune pratiche concrete per esplorare lo "spazio" e le modalità della cittadinanza attiva nelle politiche per la qualità urbana e il benessere
Current role of vigabatrin in infantile spasms
Vigabatrin (VGB), a selective irreversible inhibitor of g-aminobutyric acid transaminase, has proved to be effective against cryptogenic and symptomatic infantile spasms (IS). Unfortunately, reports of serious visual field defects have led to a drastic reduction in the use of the drug. This review is based on a systematic search in the literature for evidence regarding efficacy and safety of VGB in IS. Based on a specific mechanism of action, there is a solid evidence of clinical efficacy of VGB in children with Tuberous Sclerosis. Similarly, VGB could represent a potential effective therapy also for spasms due to focal cortical dysplasia. In infants with spasms due to other causes, the risk of ophthalmologic toxicity should be carefully weighted against the benefit of controlling spasms
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The validity of the ECLAM index for the retrospective evaluation of disease activity in systemic lupus erythematosus
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