L. Sun

Diffusional kurtosis imaging of parotid glands in Sjögren's syndrome: Initial findings: DKI of Parotid in Sjögren's Syndrome

To explore the role of diffusion kurtosis imaging (DKI) of parotid glands in diagnosing Sjögrens syndrome (SS).

Correlation between intravoxel incoherent motion MR parameters and MR nodular grade of parotid glands in patients with Sjögren’s syndrome: A pilot study

PURPOSE To explore the correlation between intravoxel incoherent motion (IVIM) magnetic resonance (MR) parameters and MR nodular grade of parotid glands in patients with Sjögrens syndrome (SS). MATERIALS AND METHODS A total of 31 consecutive patients with SS and 28 gender- and age-matched healthy volunteers underwent bilateral parotid 3.0T MR examination including the IVIM sequence (9 b values, 0-800s/mm2). The apparent diffusion coefficient (ADC), diffusion coefficient D, pseudo-diffusion coefficient D*, and perfusion fraction f of bilateral parotid glands were obtained, and the nodular grade of each parotid gland was evaluated according to the MR morphological appearance. RESULTS Sixty-two parotid glands in 31 patients with SS consisted of 32, 14, 8, and 8 parotid glands at MR nodular grades 0, 1, 2, and 3, respectively. In parotid glands of grade 0, 1, 2, 3 and healthy volunteers, the ADC values were (1.13±0.25, 1.11±0.17, 1.05±0.24, 0.89±0.04 and 1.00±0.21)×10-3mm2/s, D values were (0.92±0.13, 0.90±0.19, 0.90±0.03, 0.67±0.03, 0.81±0.03)×10-3mm2/s, f values were 0.20±0.04, 0.18±0.02, 0.15±0.01, 0.11±0.01, 0.15±0.06, and D*values were (53.89±28.26, 41.78±16.35, 51.24±18.69, 31.83±18.03, 36.83±16.14)×10-3mm2/s respectively. The ADC, D, f, and D* values of parotid glands in patients with SS at grade 0 were significantly higher than those in healthy volunteers (all P<0.05). Significant differences were observed in the D and f values of parotid glands in patients with SS among different grades (P=0.003,<0.001, respectively). The IVIM parameters (D, f) of parotid glands at early (grades 0-1) and advanced (grades 2-3) stages in patients with SS were significantly higher and lower, respectively, than those in healthy volunteers (all P<0.05). The D and f values inversely correlated with MR nodular grades significantly (r=- 0.297, P=0.019; r=- 0.653, P<0.001, respectively) CONCLUSION: The parotid glands with different MR nodular grades in patients with SS showed different IVIM parameters, reflecting different pathophysiological characteristics of parotid glands at different stages.

Use of T1ρMR imaging in Sjögren's syndrome with normal appearing parotid glands: Initial findings

To explore the feasibility of parotid spin‐lattice relaxation time in the rotating frame (T1ρ) MR imaging in the diagnosis of Sjögrens syndrome (SS) without morphological changes of the parotid glands.

OP0166 Il-27 Participates in Sjogren's Syndrome by Regulating Lymphocyte Subsets

Background Primary Sjogrens syndrome (pSS) is a chronic, systemic autoimmune disorder characterized by inflammation of exocrine glands and functional impairment of the salivary and lacrimal glands [1]. The pathogenesis of pSS is complicated with many respects remaining elusive. Interleukin-27 (IL-27) is a new member of the IL-12 cytokine family. It is largely secreted by activated antigen-presenting cells, such as macrophages and dendritic cells (DCs). IL-27 participates in multiple autoimmune diseases by regulating T lymphocyte subsets. Recent studies showed that IL-27 was involved in anti-inflammatory functions in SS [2]. However, the underlying mechanism of IL-27 in SS is still unknown. Objectives In the present study, the changes of lymphocyte subsets were studied in Il-27 knock-out and wild-type pSS models and pSS patients for the purpose to explore the specific mechanism of IL-27 in pSS and provide the basis for clinical treatment. Methods The NOD mice, Il-27 knockout (Il-27–/–) mice, Il-27 knockout mice with recombinant IL-27 treatment were studied. The saliva flow rates, weight, weight of submandibular glands and spleens were detected. Murine submandibular glands were fixed and paraffin sections were used for hematoxylin and eosin staining. The lymphocyte subsets of spleens from experimental mice and the peripheral blood from pSS patients were measured by flow-cytometric assay. Results Compared to WT NOD mice, the saliva flow rates decreased significantly, and the indexes of submandibular glands and spleens increased significantly in Il-27–/– mice (Fig 1A-E). The histological results showed that the number of lymphocytic infiltrates in submandibular glands of WT NOD was lower than Il-27–/– mice (Fig 1F). The splenic-Treg cells decreased significantly, but the levels of splenic Th17 and B cells increased significantly in Il-27–/– mice. After IL-27 treatment, the saliva flow rates, submandibular glands, Treg and Th17 cells were partially reversed in Il-27–/– mice (Fig 1G-M). Consistent with above observations, the changes of Terg and Th17 cells in pSS patients showed similar pattern. The Th2, Tfh and plasma cells increased significantly, whilst the B cells decreased significantly in pSS patients (Fig 1N-T). Compared with healthy control, the serum IL-27 decreased in pSS patients. Conclusions In general, these findings indicated that IL-27 deficiency deteriorated the disease symptoms of pSS and resulted in changes of Th17/Treg balance. In addition, pSS patients showed similar lymphocyte imbalance. Our data suggested that IL-27 might play an important role on the development and pathogenesis of pSS through regulating lymphocyte subsets, and targeting IL-27 and Th17/Treg balance may be a new direction of pSS treatment. References Xu J, Wang D, Liu D, et al. Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjogren syndrome. Blood, 2012, 120(15): 3142–3151. Lee BH, Carcamo WC, Chiorini JA, et al. Gene therapy using IL-27 ameliorates Sjögrens syndrome-like autoimmune exocrinopathy. Arthritis Res Ther, 2012, 14(4): R172. Disclosure of Interest None declared

Diffusion kurtosis imaging in sacroiliitis to evaluate the activity of ankylosing spondylitis: DKI for Ankylosing Spondylitis

Conventional magnetic resonance (MR) imaging is limited in providing sufficient information on microstructure or in quantitatively evaluating certain inflammation processes. Functional MR sequences such as diffusion kurtosis imaging (DKI) might help to evaluate the sacroiliac joint in ankylosing spondylitis (AS) patients.

SAT0463 Olfactory impairment in patients with primary sjÖgren’s syndrome and its correlation with organ involvement and immunological abnormalities

Background Recent findings suggest that autoimmune disorders predispose to a diminished capacity to smell. This has been shown for patients with systemic lupus erythematosus as well as for patients with rheumatoid arthritis. However, this problem has not received much attention in primary Sjögren’s syndrome (pSS). Objectives The aim of the study was to assess the olfactory functions of patients with primary Sjögren’s syndrome and to correlate these findings with their disease activity. Methods Fifty-two patients with primary SS and 52 age- and sex-matched healthy control subjects underwent clinical and laboratory examination. Olfactory functions were evaluated using olfactory function assessment by computerised testing including the three stages of smell: threshold, identification and memory of the different odours. The disease activity was assessed by the EULAR SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI). Results All the olfactory scores (odour threshold, odour memory and identification) in patients with pSS were significantly below the scores in the control group (all p<0.001). Multivariable regression analysis revealed that smell threshold score correlated negatively with ESSPRI and ESSDAI (adjusted R2=0.381, p<0.05). Smell threshold score was decreased in pSS patients with anti-SSA antibody compared with those without (p<0.05). Total smell scores were significantly reduced in patients with thyroid involvement (p<0.01). Conclusions Our findings indicate that olfactory functions are impaired in pSS patients. There was close correlation between olfactory dysfunction with disease severity and serological abnormalities. Therefore, imperative that physicians should make their patients to be aware of these sensory dysfunctions and educate them on methods to cope with it for better quality of life. References [1] Shoenfeld N, Agmon-Levin N, Flitman-Katzevman I, Paran D, Katz BS, Kivity S, et al. The sense of smell in systemic lupus erythematosus. Arthritis Rheum2009;60:1484–1487. [2] Proft F, Steinbach S, Schulze-Koops H, Hundt W, Heinrich P, Gruenke M. Gustatory and olfactory function in rheumatoid arthritis. Scand J Rheumatol2011;40:169–177. Disclosure of Interest None declared

SAT0032 Mesenchymal stem cells alleviate experimental autoimmune cholangitis through immunosuppression mediated by galectin-9

Background Mesenchymal stem cells (MSCs) play anti-inflammatory role by secreting some kinds of bioactive molecules. However, the effect of MSCs on chronic autoimmune liver disease, such as primary biliary cholangitis (PBC) and its underlying mechanism remains elusive. Objectives The aim of this study was to assess the efficacy of UC-MSCs treatment (UC-MSCT) in 2OA-BSA-induced murine autoimmune cholangitis and explore its underlying mechanisms. Methods UC-MSCs were transplanted into experimental autoimmune cholangitis mice. Biochemical and histological analysis were performed based on the blood and liver tissues. The immunomodulatory effects of UC-MSCs and its cytoprotective function were also investigated. Results We found that UC-MSCT significantly ameliorated liver inflammation in 2OA-BSA induced autoimmune cholangitis mice, primarily by diminishing Th1 and Th17 responses, and modifying liver chemokine activity. We also found that UC-MSCs significantly repressed the proliferation of CD4 +T cells and suppressed the differentiation of Th1 and Th17 cells, both of which were dependent on galectin-9 (Gal-9). Furthermore, we determined the signal transducer and activator of transcription (STAT) and c-Jun N-terminal kinase (JNK) signalling pathways were involved in the production of Gal-9 in MSCs. Conclusions The present study shows that UC-MSCs exert profound inhibitory effects on inflammatory responses and that they ultimately alleviate the liver injury in experimental autoimmune cholangitis mice. Further, we demonstrate that UC-MSCs inhibit Th1 and Th17 cell responses as well as aberrant chemokine activity through Gal-9 mediated immunosuppression. Additionally, our research reveals that the induction of Gal-9 in MSCs is mediated by the involvement of the STAT and JNK signalling pathways. These findings may help in the development of stem cell therapies for the treatment of PBC. Disclosure of Interest None declared

AB0063 High-efficiency transduction of mesenchymal stem cells by aav2/dj vector for their potential use in autoimmune diseases

Background Mesenchymal stem cells (MSC), multipotential non-hematopoietic progenitors, can be isolated from various tissues and can modulate allogeneic immune cell responses. These properties make MSC as a promising potential treatment of autoimmune diseases.1 Our previous studies have found that bone marrow-derived (BM)-MSC from systemic lupus erythematosus (SLE) patients are defective structurally and functionally,2 treatment with modified and optimised MSC may bring a better effect on patients with autoimmune diseases. Most efforts have relied on adeno- and lentiviral vectors for delivering genes to MSC. Effective as these vectors may be, concerns regarding their immunogenicity and, in the case of lentivirus, the risk of insertional mutagenesis, have led to the pursuit of safer alternatives. Among these, adeno-associated virus (AAV) holds several advantages as a vector for human gene therapy. There are many serotypes of AAV available, and certain serotypes have been found to transduce specific cell types more efficiently than others. Objectives To determine the efficiency of different serotypes of AAV vectors for their ability to mediate transduction of different sources of MSC and assess whether AAV transduction affects MSC multipotentiality. Methods Serotypes 1, 2, 5, 6, 8, 9, PHP and DJ of AAV vectors were constructed in Viral Core, Boston Children’s Hospital. The enhanced green fluorescent protein (eGFP) gene under transcriptional control of a CAG promoter was cloned into the AAV vector backbone. MSC derived from umbilical cord (UC), BM and amniotic fluid (AF) were isolated and approximately 1 × 105 MSC were used for transductions with AAV vectors. eGFP expression was evaluated 3 days after transduction by fluorescence microscopy and flow cytometry. The capacity of MSC to differentiate in vitro was assessed.Abstract AB0063 – Figure 1 A: the transduction efficiencies of AAVs (MOI=5:1) in AF-MSC, BM-MSC and UC-MSC, B: the transduction efficiencies of AAV/DJ in UC-MSC with different MOI. Results AAV serotype DJ vector was the most efficient in transducing MSC. AAV was added directly to the medium at 5 multiplicities of infection (MOI), 41% UC–MSC was transduced by AAV2/DJ, while the transfection is 0.47%, 0.3%, 10.5%, 0.3%, 1.84%, 0.06%, 0.16% by AAV2/1, AAV2/2, AAV2/5, AAC2/6, AAV2/8, AAV2/9, AAV2/PHP (Fig 1A). Transduction efficiencies ranged from 73.5% for MOI 10% to 91.3% for MOI 320 in UC–MSC (Fig 1B). MSC derived from different tissues share a comparable level of transduction with the same AAV vector serotype. In our result, AAV2/DJ was the most efficient in transducing UC–MSC and AF–MSC. AAV2/DJ transduced MSC retained the same multipotential activity to differentiate into osteogenic and adipogenic lineage as comparable to un–transduced cells. Conclusions AAV2/DJ vector can be used as a highly efficient tool to modify MSC ex vivo for therapeutic transplantation for autoimmune diseases. References [1] Liang J, Wang D, Dominique F, Sun L. Mesenchymal stem cells for treating autoimmune diseases: The Chinese experience from lab to clinics. Curr Res Transl Med.2016;64(2):115–20. [2] Sun L, Akiyama K, Zhang H, et al. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells2009;27(6):1421–32. Disclosure of Interest None declared

AB0643 Ft3 strongly correlates with lipid profiles and disease activity in sle patients

Background Dyslipidemia is prevalent in Systemic Lupus Erythematosus (SLE) patients and associated with lupus nephritis. Non-thyroidal illness syndrome (NTIS) frequently occurs in some autoimmune diseases. The incidence of dyslipidemia and NTIS in SLE patients vary in different studies and the association of NTIS and dyslipidemia in SLE patients has not yet elucidated. Objectives To investigate the frequency of dyslipidemia and NTIS in SLE patients and their association with laboratory parameters and SLE disease activity index (SLEDAI). To further explore the association between FT3 and blood lipid profiles in SLE patients. Methods This cross-sectional and prospective study included 271 patients fulfilled the ACR criteria for SLE. Forty-one patients who had a history of thyroid disease and/or familial hyperlipidemia and/or other rheumatologic diseases, and those took lipid-lowering agents or thyroid medications are excluded. Detailed laboratory parameters were collected and SLEDAI were assessed by qualified specialists of Rheumatology. Results Frequencies of dyslipidemia and NTIS in SLE patients are 61.8% and 57.2%, respectively. Laboratory indexes such as BUN (p<0.05), urine acid (p<0.01), CRP (p<0.001), ESR (p<0.001) and SLEDAI (p<0.05) are significantly increased in SLE patients with dyslipidemia than non-dyslipidemia. Compared to euthyroid SLE patients, SLE patients with NTIS showed substantially elevated 24 hour urine protein (p<0.001), fasting blood glucose (p<0.001), BUN (p<0.001), serum creatinine (p<0.01), uric acid (p<0.05), CRP (p<0.05), ESR (p<0.001) and SLEDAI (p<0.01). Moreover, triglyceride (p<0.01), total cholesterol (p<0.01), LDL (p<0.01) and ApoB (p<0.001) levels are markedly higher in SLE patients with NTIS than euthyroid ones, while HDL levels obviously decreased in the former group (p<0.01). More notably, the lower FT3 patients showed more severe lipid profiles and significantly higher 24 hour urine protein (p<0.001), BUN (p<0.001), serum creatinine (p<0.001), uric acid (p<0.05), and SLEDAI (p<0.05) than patients with normal FT3. FT3 levels are negatively correlated with triglyceride (r=−0.263, p<0.0001), total cholesterol (r=−0.295, p<0.0001), LDL (r=−0.273, p<0.0001) and positively correlated with HDL (r=0.180, p<0.01). Conclusions Dyslipidemia and NTIS are prevalent in SLE patients and strongly correlates with disease activity. SLE patients with NTIS are more likely to combine with dyslipidemia, FT3 levels significantly correlates with lipid profiles and FT3 may plays a protective role in dyslipidemia. References [1] Tisseverasinghe A, Lim S, Greenwood C, Urowitz M, Gladman D, Fortin PR. 2006. Association between serum total cholesterol level and renal outcome in systemic lupus erythematosus. Arthritis And Rheumatism54: 2211–9 [2] Amaya-Amaya J, Sarmiento-Monroy JC, Caro-Moreno J, Molano-Gonzalez N, Mantilla RD, Rojas-Villarraga A, Anaya JM. 2013. Cardiovascular disease in latin american patients with systemic lupus erythematosus: a cross-sectional study and a systematic review. Autoimmune Dis2013: 794383 [3] Neto AM, Zantut-Wittmann DE. 2016. Abnormalities of Thyroid Hormone Metabolism during Systemic Illness: The Low T3 Syndrome in Different Clinical Settings. International Journal Of Endocrinology [4] Watad A, Mahroum N, Whitby A, Gertel S, Comaneshter D, Cohen AD, Amital H. 2016. Hypothyroidism among SLE patients: Case-control study. Autoimmunity Reviews15: 484–6 Acknowledgements None Disclosure of Interest None declared

SAT0465 Clinical manifestations and prognosis of sle with clinically significant antiphospholipid antibodies

Background Antiphospholipid antibodies (aPLs) have been described in 20%>40% of SLE patients, with 50%>70% of patients with SLE and aPL showing the clinical features of APS after 20 years of follow-up1. It assumes that aPLs-positive SLE patients would have a more severe clinical phenotype and worse prognosis than those without aPLs. Objectives We decided to investigate the clinical manifestations and prognosis of SLE with clinically significant aPLs in a multiple centre SLE cohort. Methods A follow-up study to investigate the prognosis of SLE, has been conducted in 26 centres across Jiangsu province as described before2. SLE patients fulfilled ACR/SLICC criteria. Patients who had ever recorded first admissions and detected aPLs during the 1999±2009 decade were followed and checked for their survival status in 2015. Clinically significant aPL were defined as: positive LA test, aCL IgG/IgM antibodies>99 th percentile and/or aβ2GPI>99 th percentile on two or more occasions at least 12 weeks apart. Results 1) Among 1372 SLE patients, 495 patients was reported the aPLs minutely, and 146 cases was with clinically significant aPLs. Compared with aPLs negative SLE patients, the proportion of men, and the rates of oral ulcer, neuropsychiatric involvement, dsDNA, antinuclear antibody and C3 were significantly higher in aPLs positive SLE. (table 1) aPLs positive n=146 aPL negative n=349 P Gender (male) 5 32 0.017 Oral ulcer 29 44 0.047 Thromboembolism 16 18 0.031 Neuropsychiatric 14 20 0.000 C3 decrease 119 248 0.015 Anaemia 109 214 0.005 ANA positive 138 317 0.048 Anti dsDNA positive 83 169 0.009 2) There were 20 deaths in aPLs positive SLE group and 52 deaths in aPLs negative SLE group during the average follow up of 7.38±0.56 years and 7.54±0.0.47 years respectively. There was no significant difference in survival curves by Kaplan Meier survival analysis (p=0.776). (Picture 1) 3) Multivariate Cox regression analysis revealed that long time of diagnosis (HR 4.205, p<0.05), SDI>1 in admission (HR 11.982, p<0.01), neuropsychiatric involvement (HR 2.826, p<0.05), and increased serum creatinine (HR 8.403, p<0.01) were independent predictors of mortality. (table 2) factors Univariate Multivariate HR 95% CI P HR 95% CI P Time of diagnosis>1 year 5.26 2.24–12.32 0 4.20 1.06–16.56 0.04 SDI≥1 on admission 4.37 1.67–11.40 0.003 11.98 2.85–50.25 0.001 Neuropsychiatric 4.52 1.89–10.84 0.001 2.82 1.01–7.85 0.048 Increased serum creatinine 4.39 1.87–10.30 0.001 8.40 2.20–32.04 0.002 Conclusions In this study, we observed that around one-third of patients had clinically significant aPLs, and such autoantibody positivity was associated with a different clinical and serological profile. However, the mortality between aPLs positve and negative SLE patients had no significant difference.SLE patients presented with vital organ damages rather than active disease at initial hospitalisation are likely to have a poor outcome, especially neuropsychiatric involvements and renal insufficiency. References [1] Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. The New England journal of medicine2002;346:752–763. [2] Feng X, Pan W, Liu L, et al. Prognosis for Hospitalized Patients with Systemic Lupus Erythematosus in China: 5-Year Update of the Jiangsu Cohort. PloS One2016;11:e0168619. Disclosure of Interest None declared