Mislav Radić

Relationship between vitamin D, IFN-γ, and E2 levels in systemic lupus erythematosus.

In this study, we investigated the relationship between vitamin D, interferon-gamma (IFN-γ), and estradiol (E2) in females of childbearing age with inactive systemic lupus erythematosus (SLE). The study included 22 SLE patients, and 21 age- and gender-matched healthy individuals. Serum concentrations of 25-hydroxyvitamin D3 (25(OH)D3), E2, and IFN-γ were measured by radioimmunoassay using the gamma-counter and ELISA. Patients and control subjects were divided into two groups based on their vitamin D levels (25(OH)D3u2009≤u200920u2009ng/mL; 25(OH)D3u2009>u200920u2009ng/mL). The median values of IFN-γ and E2 were higher in SLE patients compared to the controls, irrespective of vitamin D level (pu2009=u20090.001, pu2009=u20090.009, pu2009=u20090.003, and pu2009=u20090.003, respectively). In SLE patients, there was a negative correlation between IFN-γ and 25(OH)D3 (rsu2009=u2009−0.330; pu2009=u20090.03) and a positive correlation between IFN-γ and E2 (rsu2009=u20090.404; pu2009=u20090.007). This study demonstrates an interesting interplay between vitamin D, INF-γ, and E2 in SLE patients with inactive disease.

Churg-Strauss Syndrome Associated with Montelukast Therapy

Churg-Strauss syndrome is a rare form of eosinophilic vasculitis associated with asthma. Several cases of eosinophilic conditions including Churg-Strauss syndrome have recently been reported in asthmatic patients being treated with antileukotriene receptor antagonists. However, whether these drugs have a direct pathogenic role remains controversial. We describe two patients who developed Churg-Strauss syndrome after starting treatment with montelukast.

SAT0434 Does Angiotensin and Endothelin Receptor Blockade Have an Impact on Lung Function? an Analysis from the Eustar Data Base

Background Antibodies against the angiotensin II type-1 receptor and endothelin-1 type A receptor are simultaneously present in the majority of patients with systemic sclerosis (SSc) and high levels are associated with pulmonary arterial hypertension (PAH) and lung fibrosis. It is suggested that these antibodies may contribute to lung involvement by stimulating their receptors. Thus, angiotensin receptor blockers (ATRB) and/or endothelin receptor blockers (ETRB) may exhibit beneficial effects on lung function. Objectives The objective of this study is to evaluate the possible benefit of simultaneous treatment with ETRB and ATRB. Methods SSc patients with lung fibrosis prospectively followed in the EUSTAR database and treated with ETRB and/or ATRB were analyzed with regard to the evolution of forced vital capacities (FVC) and carbon monoxide diffusing capacities (DLCO) and were compared to patients without receptor blockade. Pulmonary fibrosis was defined by evidence of fibrosis such as bibasilar fibrosis on chest radiograms or HR-CT scans or both. Patients receiving immunosuppressive therapies were excluded. To adjust for confounders, patients receiving ATRB, ETRB, or both were matched for sex, SSc subtype, disease duration, and initial FVC/DLCO values. Results 9,862 patients of the EUSTAR data base were analysed, of those, 764 patients took ETRB and 674 received ATRB. 410 of ETRB/ATRB patients had at least one annual follow-up (mean period of 13.12, SD 3.25 months). 239 patients from ETRB/ATRB group also received immunosuppressive therapies during this follow-up and were, therefore, excluded from further analyses. Finally, 31 patients with simultaneous ATRB/ETRB, 31 patients with ATRB, 31 patients with ETRB, and 31 patients not receiving any blockade were matched and compared. All patients treated with blockers fulfilled the ACR criteria. As expected, patients receiving ETRB had a higher prevalence of PAH (as suggested by echocardiography) and digital ulcers (DU), compared to those patients without blocker therapies. In contrast, the prevalence of these complications in patients receiving ATRB did not differ from the group without any blockade. Patients without any blockade unexpectedly did not show any reduction in DLCO levels during the follow up period. This reduction was prevented in patients receiving ATRB, as well as ATRB/ETRB in whom mostly stability of DLCO values was observed compared to baseline levels. There was no statistically significant improvement of predicted DLCO values by ≥10% according to treatment. There was no significant effect of ATRB or ETRB on FVC levels, although a higher proportion of patients (27.6%) showed improved FVC levels ≥10% when receiving ATRB, compared to 17.2% in the control group without blockers. Conclusions The data do not indicate a potentially beneficial effect of ATRB or ETRB on lung function parameters, especially on DLCO values. Our study is limited by its size, observational design and different disease activity and severity between groups. Further studies are warranted to elucidate the role of angiotensin and endothelin receptor blockade in possible prevention of lung function deterioration. Disclosure of Interest None declared

PS6:116 Diet habits in patients with systemic lupus erythematosus

Objective Many patients with systemic lupus erythematosus (SLE) are interested in diet advices. We wanted to investigate which diet habits are most common in our patients, and which of them are in correlation with laboratory parameters that are related to disease remission, such as normal values of serum complement and 24u2009hour proteinuria. Methods We included 76 patient with SLE in remission, in age between 21 and 75. They fulfilled 23-item questionnaire about weekly diet habits. Basic anthropometric data, disease duration, levels of C3 and C4 complement components and 24u2009hour proteinuria were recorded and analysed in correlation with diet habits. Results Majority of our patients had normal BMI (between 18.5 and 25u2009kg/m2), prefered to eat healthy food and did regular weekly workout. Milk, meat, fruits, vegetables, pasta, rice and bread were the most abundant food. Lower serum values of C3 were found in 34 (44.7%) cases, and lower values of C4 were found in 28 (36.8%) cases. Only 5 (6.6%) patients had significant 24u2009hour proteinuria higher than 3.5u2009g and another 7 (9.2%) had proteinuria higher than 1u2009g. Lower values of C3 were found in patients who often consumed meat (p=0.015) and fast food (p=0.060), and those patients who more often consumed fast food or fried food had lower levels of C4 (p=0.043u2009and p=0.051). Conclusions There is an evidence that food rich in proteins and calories can lower serum complement levels. As clinicians, we should always advice our SLE patients to eat a lot of fish, fruits and fresh vegetables, although there is no strong support for that. More studies with dietary interventions have to be done before final recommendations can be made.

FRI0481 Increased Caspase-3 Activity in the Stomach Tissue Correlates with Disease Activity and Severity in Systemic Sclerosis Patients – A Pilot Study

Background Systemic sclerosis (SSc) is an autoimmune disease characterized by chronic inflammation, vascular injury and excessive fibrosis. Apoptosis is a key mechanism involved in all the stages of the disease: vascular damage, immune dysfunction, and fibrosis. Caspases are a family of endoproteases that provide critical links in cell regulatory networks controlling inflammation and cell death. Dysregulation of caspases underlies human diseases including cancer and inflammatory disorders, and major efforts to design better therapies for these diseases seek to understand how these enzymes work and how they can be controlled. Objectives This pilot study aimed to explore the expression of caspase-3 in stomach tissue in SSc patients and possible correlation with disease activity and severity. Methods A total of thirteen stomach tissue biopsies (11 SSc and 2 controls) were collected. The same investigator, blind to clinical features, performed upper gastrointestinal endoscopy. The sections of stomach tissue were separately incubated for 45 min with rabbit anti-human/mouse active caspase-3 primary antibody. The intensity of apoptosis according to the caspase 3 activity was semiquantitatively selected into four categories: mild, moderate and abundant. We evaluated the disease activity and severity using clinical and laboratory parameters according to a modified Medsger severity scale and activity score. The disease activity was assessed according to Valentinis Scleroderma Disease Activity Index. In all the patients skin involvement was assessed by the modified Rodnan skin score (mRSS). The study was approved by the University Hospital Split Ethics Committee. Results Eleven SSc female patients [mean age 54.3 (13.6) years, median disease duration 13 years with minimum–maximum range 1–35 years] were enrolled in this study after they gave written informed consent. All patients fulfilled the ACR criteria for the diagnosis of SSc. Five SSc patients had moderate/abundant and six had mild apoptosis on the basis of the caspase 3 activity. In SSc patients, the number of apoptotic cells is high, and their distribution is observed in several layers of the stomach wall, including blood vessels (Figure 1). The skin involvement and disease duration were highly different between SSc patients regarding to the apoptosis level (P<0.05, P<0.05, Mann–Whitney test). No significant difference was found for autoantibody profile between SSc patients regarding apoptosis levels of stomach tissue. Disease activity and severity were higher in SSc patients with moderate/abundant apoptosis of the stomach tissue (P<0.05, P<0.05, Mann-Whitney test). Figure 1. Normal mucosa of the stomach: columnar surface epithelium (e), connective tissue lamina propria (lp), glands (g) (A); brown-staining nuclei and nuclear fragments of caspase-3 positive apoptotic cells in the lamina propria. Immunohistochemical staining to caspase-3 (B); part of lymphocyte accumulation and blood vessel (bv), both contacting numerous apoptotic cells (arrows) (C). Conclusions In SSc patients we have showed increased caspase-3 activity (cell death) in the stomach tissue. Increased cell death in the stomach tissue correlates with disease duration, activity, severity and skin involvement. Disclosure of Interest None declared

AB0613 Clinical and Laboratory Differences between SSC Patients with and without Diastolic Dysfunction

Background Left ventricular diastolic dysfunction (LVDD) is the most common cardiac abnormality in systemic sclerosis (SSc). It is known that aging is a primary determinant of LVDD in SSc patients and many of the clinical factors associated with LVDD were no longer associated after simply adjusting for age. Objectives The aim of this study was to determine clinical and laboratory parameters of SSc patients with and without LVDD matched for age. Methods We studied 13 SSc patients with preserved left ventricular ejection fraction (LVEF) and LVDD, and 13 SSc patients without LVDD matched for age, sex, body mass index and smoking status. LVDD was defined and classified according to the American Society of Echocardiography recommendations. Serum IL-6 and NT-proBNP levels were measured and subjects were evaluated by conventional and pulsed-wave tissue Doppler echocardiography and by the six minute walk test (6MWT). Results There was no difference between SSc patients with and without LVDD according to heart rate, systolic and diastolic blood pressure, left ventricular mass index, prevalence of pulmonary artery hypertension, and antibody status. SSc patients with LVDD had longer duration of SSc than SSc patients without LVDD (16.0 vs 6.65 yrs; P=0.004), and had higher EUSTAR score (5.77 vs 3.12; P=0.001). The serum level of IL-6 (6.39 vs 2.94 pg/ml; P=0.021) and NT-proBNP (24.78 vs 10.12 pmol/L; P=0.003) were significantly increased in SSc patients with LVDD. The 6MWT distance was shorter in SSc patients with LVDD as compared to those without LVDD (326.46 vs 398.69 m; P=0.034). Also, desaturation during the 6MWT was more significant in SSc patients with LVDD (-3.38% vs -1.92%; P=0.022). Conclusions SSc patients with LVDD had longer disease duration and higher disease activity (EUSTAR) scores. SSc patients with LVDD showed significantly increased serum IL-6 and NT-proBNP levels in comparison with those without LVDD. LVDD is associated with decreased exercise capacity in SSc patients. References Hinchcliff M, Desai CS, Varga J, Shah SJ. Prevalence, prognosis, and factors associated with left ventricular diastolic dysfunction in systemic sclerosis. Clin Exp Rheumatol. 2012;30:30-7. Scala E, Pallotta S, Frezzolini A et al. Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement. Clin Exp Immunol 2004;138:540-6. Nagueh SF, Appleton CP, Gillebert TC et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 2009;22:107-33. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5652