Baris Gundogdu

Coexistence of Ankylosing Spondylitis and Neurofibromatosis Type 1

Ankylosing spondylitis (AS) is a systemic disease primarily characterized by the inflammation of sacroiliac joints and axial skeleton. Neurofibromatosis type 1 (NF1) is a multisystem genetic disease which is characterized by cutaneous findings, most importantly café-au-lait spots and axillary freckling, by skeletal dysplasia, and by the growth of both benign and malignant nervous system neoplasms, most notably benign neurofibromas. In this case report, we present a 43-year-old male with AS and NF1.

ENHO gene expression and serum adropin levelin rheumatoid arthritis and systemic lupus erythematosus

BACKGROUND Adropin, a secreted protein, is encoded by the energy homeostasis-associated gene (ENHO). It is expressed by a variety of tissues and cells. It has been implicated in several physiological and pathological processes, such as angiogenesis and apoptosis. OBJECTIVES The aim of the present study was to investigate the ENHO gene expression and serum adropin levels in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). MATERIAL AND METHODS The study included 36 patients with RA, 22 patients with SLE and 20 healthy controls (HC). Patients with a disease activity score-28-erythrocyte sedimentation rate (DAS28-ESR) >2.6 in the RA group and an SLE disease activity index (SLEDAI) >6 in the SLE group were accepted as active. Serum adropin levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) method. The ENHO gene and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expressions in peripheral blood mononuclear cells were analyzed by real-time polymerase chain reaction (PCR). RESULTS The ENHO gene mRNA expression was significantly higher in the RA group than in the HC group (p = 0.024), although it was similar between the SLE and HC groups (p = 0.920). On the other hand, there were no significant differences among the study groups in terms of serum adropin levels (p > 0.05 for all). Moreover, there was no significant difference in terms of the ENHO expression and serum adropin levels between active and inactive RA and SLE patients. CONCLUSIONS Although the ENHO gene expression is increased, serum adropin level is not altered in RA. Similarly, adropin seems not to be associated with SLE. However, the potential link between adropin and inflammatory diseases need to be tested by further studies.

Serum osteopontin and vitronectin levels in systemic sclerosis

BACKGROUND Osteopontin a matricellular protein has pro-fibrotic effects and binds integrin such as αvβ1 and αvβ3. Vitronectin is one of the integrin αvβ3 ligands and is a multifunctional glycoprotein. OBJECTIVES The aim of the present study was to evaluate serum osteopontin and vitronectin levels in a cohort of patients with systemic sclerosis (SSc). MATERIAL AND METHODS Eighty-six patients with SSc, 46 patients with systemic lupus erythematosus (SLE), and 38 healthy controls (HC) were enrolled in the study. Serum osteopontin, vitronectin, IL-6, and TGF-β levels were analyzed. RESULTS Serum osteopontin levels were higher in the SSc and SLE groups compared to the HC group (p < 0.01 and p < 0.001, respectively). However, it was not correlated with disease activity and severity scores in the SSc group. On the other hand, serum vitronectin levels were lower in the SSc group than in the SLE and HC groups (p < 0.001 for both). CONCLUSIONS These results may suggest that osteopontin levels may be increased due to the inflammatory process and osteopontin has not a specific role on fibrosis in SSc. On the other hand, serum vitronectin levels decrease in SSc in contrast to SLE. It may be concluded that the one cause of decreased serum vitronectin levels in SSc may be its accumulation in fibrotic area.

AB0728 Serum Osteopontin and Vitronectin Levels in Systemic Sclerosis

Background Osteopontin (OPN) a member of specialized matricellular protein has pro-inflammatory and pro-fibrotic effects and binds integrin such as αvβ1 and αvβ3. Vitronectin (VTN), one of the integrin αvβ3 ligands, is a multifunctional glycoprotein that is present in blood and in the extracellular matrix. Decreased levels of VTN have been reported in patients with meningococcal disease, rheumatoid arthritis and Behçets disease. Objectives The aim of the present study was to evaluate serum OPN and VTN level in systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Methods Eighty-six patients with SSc, 46 patients with SLE, and 38 healthy controls (HC) were enrolled in the study. The disease activity and severity scores in SSc group were determined by modified Rodnan skin score, Valentini activity index, Medsger disease severity index, and United Kingdom function score. In addition to routine laboratory parameters, OPN, VTN, interleukin-6, and transforming growth factor (TGF)-β levels were analyzed. Results Serum OPN levels were higher in SSc and SLE groups compared to HC group (Table and Figure). However, OPN levels in SSc group were not associated with disease activity and severity scores (p>0.05). In addition, it was not correlated with SSc specific laboratory parameters, and capilleroscopic findings. On the other hand, serum VTN level was lower in the SSc group than in SLE and HC groups, while its level was similar in the SLE and HC groups (Table). Its level was negatively correlated with modified Rodnan skin score, visual analogue scales (physician and patient), lung-Medsger and heart-Medsger scores (r=-0.256, p=0.016, r=-0.450, p<0.001; r=-0.321, p=0.003; r=-0.319, p=0.003 and r=-0.245, p=0.023, respectively).Table 1. The demographics and laboratory parameters in the study groups SSc (n=86) SLE (n=46) HC (n=38) Age (year) 51.2±12.7xxx† 34.3±9.9x 44.2±14.2 Sex (Females, %) 93 91 53 ESR (mm/h) 27.8±16.8x 39.1±28.9x 18.1±15.8 CRP (mg/dl) 1.73±3.84xxx† 0.74±1.32 0.93±2.72 IL-6 (pg/ml) 22.9±59.4 16.8±54.1xxx 5.3±3.3 TGF-β (pg/ml) 41.1±109.7xx†† 15.3±20.6 23.1±52.3 Osteopontin (ng/ml) 26.7±15.3xxx††† 36.9±18.6x 19.6±6.4 Vitronectin (ng/l) 252.6±169.1x† 501.4±487.7 526.1±357.2 When compared to the HC group;x p<0.001,xx p<0.01,xxx p<0.05. When compared to the SLE group;† p<0.001,†† p<0.01,††† p<0.05. Conclusions OPN levels are increased in SSc and SLE. These results may suggest that OPN has not a specific role on fibrosis in SSc and that OPN level may be increases due to inflammatory process. On the other hand, serum VTN level decreases in SSc in contrast to SLE and it is negatively correlated with modified Rodnan skin score. Therefore, it may be concluded that VTN has anti-fibrotic action or the one cause of decreased serum VTN level in SSc may be the accumulation in fibrotic area. Disclosure of Interest None declared

AB0212 Decreased Serum Vitronectin Level in Systemic Sclerosis

Background Vitronectin, one of the integrin αvβ3 ligands, is a multifunctional glycoprotein that is present in blood and in the extracellular matrix. Decreased levels of vitronectin have been reported in patients with meningococcal disease, rheumatoid arthritis and Behçets disease. Objectives The aim of the present study was to evaluate serum vitronectin level in systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Methods 86 patients with SSc and 46 patients with SLE and 38 healthy volunteers (HC) were included in the study. Serum IL-6, TGF-β and vitronectin levels were analyzed by ELISA method. Results The level of vitronectin was lower in the SSc group compared to the SLE and HC groups (p<0.001 for both), while its level was similar in the SLE and HC groups (Table). Although vitronectin level was not different between the diffuse and limited cutaneous subtypes of SSc (p=0.390), its level was negatively correlated with modified Rodnan skin score (r=-0.256, p=0.016). Serum vitronectin level was negatively correlated with visual analogue scales (physician and patient), lung-Medsger and heart-Medsger scores, too (r=-0.450, p<0.001; r=-0.321, p=0.003; r=-0.319, p=0.003 and r=-0.245, p=0.023, respectively). Sex, the positivity of anti-sentromer and anti-Scl-70 antibodies, and the presences of pulmonary fibrosis, pulmonary arterial hypertension and digital ulcer were not altering the serum vitronectin level. Table 1. The demographics and laboratory parameters in the study groups SSc (n=86) SLE (n=46) HC (n=38) Age (year) 51.2±12.7***† 34.3±9.9* 44.2±14.2 Sex (Females, %) 93 91 53 ESR (mm/h) 27.8±16.8* 39.1±28.9* 18.1±15.8 CRP (mg/dl) 1.73±3.84***† 0.74±1.32 0.93±2.72 IL-6 (pg/ml) 22.9±59.4 16.8±54.1*** 5.3±3.3 TGF-β (pg/ml) 41.1±109.7**† † 15.3±20.6 23.1±52.3 Vitronectin (ng/l) 252.6±169.1*† 501.4±487.7 526.1±357.2 When compared to the HC group; *p<0.001, **p<0.01, ***p<0.05. When compared to the SLE group; †p<0.001, ††p<0.01, †††p<0.05. Conclusions Serum vitronectin level decreases in SSc in contrast to SLE. Fibrosis is the main difference of SSc from SLE. Therefore, it may be concluded that the one cause of decreased serum vitronectin level in SSc may be fibrogenesis. It has been demonstrated previously that vitronectin accumulates in fibrotic area in an experimental model of renal fibrosis. Moreover, the negative correlation between serum vitronectin level and modified Rodnan skin score support this conclusion. References Schvartz I, et al. Int J Biochem Cell Biol. 1999;31(5):539-44. Høgåsen K, et al. Infect Immun. 1994;62(11):4874-80. Horton MA. Int J Biochem Cell Biol. 1997;29(5):721-5. Wilder RL. Ann Rheum Dis. 2002;61(Suppl 2):i96-9. Koca SS, et al. Rheumatol Int. 2013 Dec 28. [Epub ahead of print] Lόpez-Guisa JM, et al. Am J Physiol Renal Physiol. 201;300(5):F1244-54. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4856

AB0019 Change in MRNA Expression of Sirtuin-2 and Sirtuin-3 in Rheumatoid Arthritis

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease. Sirtuins (SIRTs) are class III histone deacetylase and mammalian SIRT family has seven members, named SIRT1 to SIRT7. SIRTs act epigenetic roles via histone modification, and alter several intracellular signal pathways including NF-κB and MAPK. Accumulating data indicate that SIRTs can affect both innate and adaptive immune responses. Objectives The aim of the present study was to evaluate the expressions of SIRT2 and SIRT3 in the patients with RA and to determine their potential effects on the disease phenotype. Methods Fifty-four patients with RA fulfilled ACR-EULAR 2010 classification criteria, and 26 healthy volunteers were enrolled in the study. Disease activity status was determined by the disease activity score (DAS)28-erythrocyte sedimentation rate and patients with >2.6 score were accepted as active. SIRT2, SIRT3 and GAPDH expressions were investigated in peripheral blood mononuclear cells with real-time PCR. Changes in gene expression are represented as fold change relative to one, where control equals one. Results The SIRT2 expression was higher (1.21±0.05 vs. 1.15±0.07 AU, p<0.001), but the SIRT3 expression was lower (1.05±0.1 vs. 1.18±0.05 AU, p<0.001), in the RA group than in the healthy control group (Figure). However, the SIRT2 (1.19±0.05 vs.1.23±0.04, p=0.01) and SIRT3 (1.01±0.03 vs. 1.10±0.13, p=0.03) expressions were lower in the active RA patients (n=28) than in inactive ones (n=26). On the other hand, their expressions were not significantly correlated with the ESR and the level of CRP (p>0.05 for all). Similarly, their expressions were not significantly different in the patients with and without anti-CCP positivity (p>0.05 for both). Although the SIRT2 expression was similar in the RF positive and negative patients (1.21±0.05 vs. 1.20±0.05 AU p=0.343) the expression of SIRT3 was increased in the former group (1.08±0.13 vs. 1.01±0.03 AU p=0.014). The SIRT3 expression was higher in the patients receiving corticosteroid (n=39) compared to the not receiving (n=15) (1.06±0.05 vs. 1.01±0.03, p=0.019) although the SIRT2 expression was not significantly different (p>0.05). The uses of methotrexate, sulphasalazine and antimalarial were not altering the SIRT2 and SIRT3 expression (p>0.05 for all). Unfortunately, their expressions were not directly correlated with any laboratory and clinical parameters. SIRT2 expressions are higher in the active (DAS28>2.6) inactive (DAS28<2.6) and all RA patients than in HCs (A). Conversely, SIRT3 expressions are lower in the former groups (B). However, SIRT2 and SIRT3 expressions are decreased in the active patients compared to the inactive ones (A and B). Figure 1. SIRT2 and 3 expressions in the HC and RA groups. Conclusions The SIRT2 expression increases, while the SIRT3 expression decreases in RA. On the other hand, the expressions of SIRT2 and SIRT3 decrease in the active stage of the disease. Therefore, it may be concluded that the fortune of each SIRT is divergent in RA. References Karouzakis E, et al. Nat Rev Rheumatol. 2009;5(5):266-72. Carafa V, et al. Front Pharmacol. 2012;3:4. Gallí M, et al. Biochem Pharmacol. 2011;81(5):569-76. Fernandes CA, et al. Biochem Biophys Res Commun. 2012;420:857-61. Lin J, et al. Biochem Biophys Res Commun. 2013;441:897-903. Lee HS, et al. Arthritis Rheum. 2013;65:1776-85. Acknowledgements NONE Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3564

THU0489 Enho Gene Expression and Serum Adropin Level in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Table 1.

Background Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are chronic inflammatory diseases. Adipokines, including leptin, adiponectin, resistin, and visfatin have been studied widely in chronic inflammatory diseases due to the metabolic, cardiovascular and inflammatory actions of adipokines. Adropin, a secreted protein, is encoded by the Energy Homeostasis Associated (ENHO) gene. It is expressed by a variety of tissues and cells. It has been implicated in the several physiological and pathological processes such as angiogenesis and apoptosis. Objectives The aim of the present study was to investigate the ENHO gene expressions and serum adropin levels and in patients with RA and SLE. Methods The study included 36 patients with RA, 22 patients with SLE, and 20 healthy controls (HC). The patients were fulfilling the established classification criteria. Disease activity statuses were determined by the disease activity score (DAS)28-erythrocyte sedimentation rate in the RA group (patients with >2.6 score were accepted as active) and SLE disease activity index (SLEDAI) in the SLE group (patients with >6 score were accepted as active). Serum adropin levels were analyzed by ELISA method using an appropriate commercial kit. ENHO and GAPDH gene expressions by peripheral blood mononuclear cells were analyzed by real-time PCR. Results ENHO gene mRNA expression was significantly higher in the RA group than in HC group (p=0.024, Table), although it was similar in the SLE and HC groups (p=0.920). On the other hand, there was no significant differences among the study groups in terms of serum adropin levels (p>0.05, for all). Moreover, there was no significant difference in terms of ENHO expression and serum adropin level between active (n=17) and inactive (n=19) RA patients, and between active (n=13) and inactive (n=9) SLE patients. Table 1. The demographics and laboratory parameters RA (n=36) SLE (n=22) HC (n=20) Age (year) 49.6±15.9† † † 31.1±8.8** 44±13 Sex (females, %) 78 95 85 BMI (kg/m2) 27.4±6.2† 23.7±4.8 27.1±4.8 ESR (mm/h) 32.7±25.0* 38.3±29.5** 17.2±11.6 CRP (mg/dl) 1.7±3.1 0.6±1.4 0.3±0.2 TC (mg/dl) 163.3±38.5* 151.5±32.8** 191.1±50.5 Triglyceride (mg/dl) 92.6±48.5** 112.6±65.9 150.3±79.6 LDL-C (mg/dl) 104.2±32.6* 96.9±24.3** 129.4±43.8 HDL-C (mg/dl) 48.6±13.2 48.1±17.7 47.6±11.6 Serum adropin (ng/ml) 1.1±0.9 1.1±0.6 0.8±0.5 ENHO expression (AU) 1.25±0.11 * 1.19±0.12 1.18±0.10 When compared to the HC group * p<0.05, ** p<0.01, *** p<0.001. When compared to the SLE group † p<0.05, † † p<0.01, † † † p<0.001. Conclusions Although ENHO gene expression is increase, serum adropin level is not altered in RA. Similarly, adropin seems not to be associated with SLE. However, the potential link between adropin and inflammatory diseases may be tested by a further study. References Krysiak R, et al. Eur J Nutr 2012;51:513-28. Lovren F, et al. Circulation. 2010;122:185-92. Aydin S, et al. Mol Cell Biochem. 2013;380:73-81. Ganesh Kumar K, et al. Obesity (Silver Spring). 2012;20(7):1394-402. Topuz M, et al. J Investig Med. 2013;61(8):1161-4. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5252

AB0709 Are Sleeping Positions Affect the Disease Activity of Ankylosing Spondylitis

Background Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting primarily the axial skeleton. Inflammatory back pain, spinal stiffness and limited spinal mobility are the characteristics AS, and can lead to structural and functional impairments and a decrease in quality of life. Sleep disturbances have been reported to be more frequent in AS than in the normal population and other rheumatic diseases. Sleep disturbances are greatly associated with the inflammatory back pain, stiffness, disease activity, depression, quality of life and the limitation of mobility in patients with AS. Sleeping positions can affect and/or can reflect sleeping disturbances. Objectives The aim of the study was to evaluate sleeping positions and sleep disturbances in patients with AS. Methods Seventy-seven patients with AS and 46 healthy volunteers (healthy control [HC] group) were enrolled in the study. Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Quality of Life Scale (ASQOL) and visual analogue scale (VAS) were applied in the AS group. The Hospital Anxiety and Depression Scale (HADS) including depression subscale (HADS-D) and anxiety subscale (HADS-A), Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) were applied in the both groups. Most common sleeping postures (foetus, yearner, log, soldier, free-fall and star-fish) were noted. Results There was no significant difference between the AS and HC groups in terms of sleeping positions (p=0.347, Table). In the AS group, disease durations, acute phase reactants levels, BASDAI, BASFI, BASMI, HAQ, PSQI, ISI, HADS-A, and HADS-D scores were similar among the patients preferred different positions (p>0.05 for all). On the other hand, the ASOqL, VAS, and patient global assessment scores were higher in the AS patients preferred foetus position than in yearner position (p=0.008, p=0.001, and p=0.01, respectively). The selections of positions of active and inactive patients were also similar (p>0.05). In the AS group, total PSQI (8.03±4.64 vs. 5.86±2.54, p=0.004) and ISI (9.71±7.40 vs. 7.14±6.14, p=0.038) scores were higher than in the HC group. Moreover, active patients had total PSQI (10.07±4.41 vs. 4.68±2.66, p<0.001) and ISI (12.17±7.28 vs. 5.00±4.96, p<0.001) compared to the inactive ones. Table 1. Preferred sleeping positions AS (n=77) HC (n=49) Yearner position, n (%) 19 (24.7) 17 (34.7) Starfish position, n (%) 5 (6.5) 3 (6.1) Log position, n (%) 5 (6.5) 5 (10.2) Soldier position, n (%) 4 (5.2) – Free-faller position, n (%) 12 (15.6) 10 (20.4) Foetus position, n (%) 30 (39.1) 14 (28.6) Other positions, n (%) 2 (2.6) – Conclusions Sleeping disturbance is a trouble in patients with AS compared to the healthy ones and in active AS patients compared to the inactive ones. However, sleeping positions seem not to affect neither sleeping disturbance nor disease activity, in AS. References Braun J, Sieper J. Lancet 2007;369:1379-90. Abad VC, Sarinas PSA, Guilleminault G. Sleep Med Rev 2008;12:211-22. Batmaz I, et al. Rheumatol Int 2013;33:1039-45. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4865