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We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden ( n =344) and Norway ( n =196) and 532 controls ( n =319 Swedish, n =213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 ( EBF1 ) gene, P =9.9 × 10 −5 , OR 1.68, the family with sequence similarity 167 member A–B-lymphoid tyrosine kinase ( FAM167A–BLK ) locus, P =4.7 × 10 −4 , OR 1.37 and the tumor necrosis factor superfamily ( TNFSF4 = Ox40L ) gene, P =7.4 × 10 −4 , OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1 , BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.

Background Ultrasound (US) represents a non-invasive imaging method of the major salivary glands that may serve as a supplement to minor salivary gland biopsy. Minor salivary gland biopsy is part of the diagnostic process for primary Sjögren’s syndrome (pSS), but is not suitable for repeated follow-up. Objectives To investigate if parotid and submandibular gland ultrasonography findings may contribute to pSS diagnosis and in the assessment of glandular function and disease activity. Methods Ultrasound of the parotid and submandibular glands was performed with a GE Logiq E9 using a linear transducer with 6-15MHz. The parotid glands were evaluated in a longitudinal and cross-sectional plane and the submandibular glands in a longitudinal plane. Glandular homogeneity and presence of hypoechogenic areas was evaluated and scored (0-3) according to Hocevar et al 2005 (1). Scores 0-1 were considered “normal” and scores 2-3 “pathological”. Salivary gland functional capacity was evaluated by unstimulated and stimulated sialometry of whole saliva, in ml/15 minutes and ml/5 minutes, respectively (n=21). Ultrasound scores were compared to sialometric findings and minor salivary gland focus score where such data was available. Results Results: Ultrasound was performed in 20 patients, with scores ranging 0-1 (n=10) and 2-3 (n=10). Mean unstimulated and stimulated saliva were 1.1 ml/15 min and 3.3 ml/5 min, respectively, and levels correlated (p<0.001, r=0.726, n=21). Ultrasound scores correlated with unstimulated (p<0.001, r=0.721, n=20) and stimulated saliva (p<0.05, r=0.546, n=20). Mean unstimulated and stimulated saliva levels were higher in patients with normal ultrasound findings compared to pathological (p<0.05). 10/14 patients with unstimulated saliva ≤1.5ml/15 min had pathological ultrasound changes compared to 0/6 with normal unstimulated saliva (p<0.01). 9/12 with stimulated saliva ≤3.5ml/5 min had pathological ultrasound compared to 1/8 with normal stimulated saliva (p<0.01). Focus score was available in 17/21 patients (mean 2.1, range 0-7), and was ≥1 in 14/17 patients. Focus score correlated with ultrasound score (p<0.05, r=0.516, n=16) and mean focus score was 3.3 in patients with ultrasound pathology and 1.2 in patients with normal ultrasound (p<0.05). Conclusions In a small cohort of patients with pSS findings from non-invasive imaging method ultrasound correlate with glandular function and minor salivary gland inflammation. Ultrasound of major salivary glands may become a useful tool in both diagnostics and follow-up of patients with pSS. References Hocevar A, Ambrozic A, Rozman B, Kveder T, Tomsic M. Ultrasonographic changes of major salivary glands in primary Sjögren’s syndrome. Diagnostic value of a novel scoring system. Rheumatology (Oxford). 2005 Jun;44(6):768-72. Disclosure of Interest None Declared

Background The diagnosis of primary Sjögren’s Syndrome (pSS) relies on invasive or non-specific tests, such as salivary gland biopsy, sialometry, sialography or scintygraphy. Ultrasonography (US) has become widely available for rheumatologists and parotid gland evaluation is easy to learn, rapidly performed, repeatable, non-invasive and non-radiating. Objectives Pilot study to explore the diagnostic utility of parotid gland US and its potential to identify patients with high disease activity or risk for systemic disease complications. Methods US of parotid glands was performed scoring parenchymal inhomogeneity as 0 = completely normal, 1 = slight abnormalities/few hypoechogenic areas, 2 = multiple hypoechogenic areas or 3 = many or confluent hypoechogenic lesions 1. Assessment of EULAR SS Disease Activity Index (ESSDAI), presence of autoantibodies and immunoglobulin levels were assessed in pSS patients. PSS patients, disease controls and healthy persons completed the EULAR SS Patient Reported Index (ESSPRI) VAS scale for dryness simultaneously. Salivary gland biopsies were assessed with regard to focal sialadenitis and Germinal Centre (GC)-like structures by routine staining and light microscopy, when available. Results Parotid glands of 77 pSS patients fulfilling the American European Consensus Criteria and of 28 controls (healthy n=7, sicca syndrome n=9, chronic arthritis n=7, systemic vasculitis or connective tissue disease n=5) were studied. 51% of the pSS patients and none of the controls showed the characteristic pattern of multiple or confluent hypoechogenic rounded lesions typical for pSS, (p<0.001). Patients with SS-typical US pattern (score 2-3) had significantly higher ESSDAI score (9.1 vs. 3.4) and IgG levels (23.0 vs. 15.3g/l) (both p<0.001), significantly more often a history of systemic disease (80% vs. 50%, p=0.007), autoantibodies to Ro and La (95% vs. 53%, p<0.001) and GC-like structures in the salivary gland biopsy (53% vs. 18%, p=0.022). Trends were seen towards lower levels of complement factor C3 and C4. No difference was found in the presence of focal sialadenitis and in dryness severity. Conclusions US of the parotid gland is a non-radiating, easy to perform and rapid bedside investigation. The typical pattern of multiple hypoechogenic lesions has high specificity for pSS and might be suitable as substitute for the more invasive parotid sialography or less specific scintygraphy within the classification criteria. Furthermore patients with these lesions have higher disease activity and more severe histological aberrations and may be at risk for lymphoma development. References Hocevar A, Ambrozic A, Rozman B, Kveder T, Tomsic M. Ultrasonographic changes of major salivary glands in primary Sjogren’s syndrome. Diagnostic value of a novel scoring system. Rheumatology (Oxford) 2005;44:768-72. Disclosure of Interest None Declared

BackgroundPrimary Sjögren's syndrome (pSS) is an autoimmune inflammatory disease predominantly affecting the salivary and lacrimal glands. The main symptoms are dryness of the mouth and eyes. The diagnosis of pSS is based on 6 items according to the American-European consensus group (AECG) classification criteria. Interest regarding ultrasonography (US) as a diagnostic tool for pSS has increased over the last years. However, the applied scoring-systems vary and as of yet international consensus on how to perform the evaluation are lacking. Consequently, the examination and evaluation depends on the examiners skill and experience. In both clinical work and a scientific setting there is a need to use objective methods with as little inter- and intra-examiner variation as possible.ObjectivesThe aim of this study was to develop a software able to analyze changes in digitally stored US images of the major salivary glands.MethodsDigitally stored US images of glandula parotis (n=94) were blindly evaluated and scored as “normal” or “SS-like” by three independent clinical researchers. At least 2/3 evaluations had to be in agreement to classify the image. All images were from patients fulfilling the AECG criteria. Images had been obtained by six clinical investigators using similar protocols on different US machines. For the analysis, images were divided into databases of SS-like changes and normal-appearing morphology. The image classification and analysis was performed using the ScatNet (v.02) algorithm (Ref: http://www.di.ens.fr/data/software/)for MatLab, which is an algorithm for advanced pattern recognition. Images from the databases were randomly selected to be used as either “training” images or “test” images. Each database of “training” images was analysed, and features of pathological and non-pathological morphology were identified by the software. For the software test, the algorithm analyses which of the databases of training images are most similar to the test images and decides in which group the test images belong. This selection was then compared to the manual scoring.ResultsOut of the 94 images evaluated, 40 were classified as normal-appearing and 54 as corresponding to SS-like pathological changes. In the preliminary simulations we have used the following training: test ratios 84:10 (90%), 70:24 (75%) and 47:47 (50%), to respectively train the classification algorithm, and then test the algorithm. The best result with 9/10 correctly classified (92% accuracy) was obtained using 90% of the images to train the software and 10% to test the software. Using 75% or 50% of the images to train the software, the accuracy was reduced to 21/24 (88%) and 25/36 (78%), respectively.ConclusionsPreliminary results indicate that the success rate of the algorithm is closely dependent on the number of images used to train the algorithm. The results are promising and indicate possible clinical use in the evaluation of SGUS images. We will further focus on expanding the image database to achieve more precise results.Disclosure of InterestNone declared

Thiamine is a vitamin that has been shown to act as a trigger to activate plant defence and reduce pathogen and nematode infection as well as aphid settling and reproduction. We have here investigated whether thiamine treatments of seeds (i.e. seed dressing) would increase plant resistance against aphids and whether this would have different effects on a generalist than on specialist aphids. Seeds of wheat, barley, oat and pea were treated with thiamine alone or in combination with the biocontrol bacteria Pseudomonas chlororaphis MA 342 (MA 342). Plants were grown in climate chambers. The effects of seed treatment on fecundity, host acceptance and life span were studied on specialist aphids bird cherry-oat aphid (Rhopalosiphum padi L.) and pea aphid (Acyrthosiphon pisum Harris) and on the generalist green peach aphid (Myzus persicae, Sulzer). Thiamine seed treatments reduced reproduction and host acceptance of all three aphid species. The number of days to reproduction, the length of the reproductive life, the fecundity and the intrinsic rate of increase were found reduced for bird cherry-oat aphid after thiamine treatment of the cereal seeds. MA 342 did not have any effect in any of the plant-aphid combinations, except a weak decrease of pea aphid reproduction on pea. The results show that there are no differential effects of either thiamine or MA 342 seed treatments on specialist and generalist aphids and suggest that seed treatments with thiamine has a potential in aphid pest management.

Objectives Ultrasonography of salivary glands is a new test to diagnose primary Sjögren syndrome (pSS)1. We assess the diagnostic value of ultrasonographic abnormalities of salivary gland in pSS using a systematic review of literature Methods PUBMED and EMBASE databases were searched. The following association of MeSh terms was used: “SALIVARY GLANDS” AND “SJOGREN’S SYNDROME” AND “ULTRASONOGRAPHY”. All publications between January 1988 and January 2013, in English language and concerning patients addressed for suspected or established pSS were considered. Sensitivity and specificity of US were collected or calculated when possible. Data were extracted from the articles meeting the inclusion criteria, focused on the US definition of scoring systems used, and metric properties studied. The type and number of glands tested, study design, and quality of the studies were assessed. Results 167 publications were identified with EMBASE and 182 with PUBMED. 30 articles were selected. The number of pSS included patients varied from 20 to 150. In most of the studies (19/30), sensitivity and specificity to detect US abnormalities were performed in established pSS. Sensitivity ranged from 44.2 % to 86 % and specificity from 73 % to 100%. Specificity was > 90 % in 12 studies.US examination was performed for diagnosis, in suspected pSS in only 5 studies 1-5, the sensitivity ranged from 58.8% to 87% and specificity from 90% to 98.7%. The parotid and submandibular glands were the most commonly studied. The scoring system is heterogeneous using 5 differents scoring systems. The echostructure abnormalities in B mode were relatively homogeneous but few studies concerned the assessment of the vascularisation. In one study, the sensitivity and the sprecificity of the US technique increased with the addition of the color Doppler. The reliability was done in 10/30 studies and only for interobserver acquisition (most often between 2 sonographers) with a kappa varying from 0.8 to 0.95. Most of the studies were performed in a single center. Conclusions This systematic review shows that very few studies are available to estimate the diagnostic value of US-pSS for suspected pSS. US in B mode had a high specificity but a high heterogeneity concerning the definition of abnormalities. The data concerning the use of Doppler are very scarce. Reliability of this technique is poorly investigated. Effort should be made to validate and standardized US in pSS. References Cornec D, Jousse-Joulin S, Pers JO et al. Arthritis Rheum. 2013 Jan;65(1):216-25. Takagi Y, Kimura Y, Nakamura H et al Ann Rheum Dis. 2010 Jul;69(7):1321-4. Milic VD, Petrovic RR, Boricic IV et al. J Rheumatol. 2009 Jul;36(7):1495-500. Shimizu M, Okamura K, Yoshiura K et al. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Oct;106(4):587-94. Hocevar A, Rainer S, Rozman B et al. Eur J Radiol. 2007 Sep;63(3):379-83 Disclosure of Interest: None Declared

Background Ultrasonography (US) of salivary glands is a relatively new test to diagnose primary Sjögren syndrome (pSS)1-2. In 2012, an international group of interest was formed to address the metric qualities of US as a potential outcome measure. A preliminary systematic review highlighted the deficiencies, particularly with regard to the reliability of interpreting and acquiring images and to delineate which abnormalities should be scored. Objectives The purpose of this study group is to improve reliability and to evaluate several US abnormalities in salivary gland in pSS. Methods We report here the first part of the study by the group that was conducted in Washington in November 2012. The first meeting bring together an international group of 7 experts in ultrasongraphy of the salivary gland in pSS and aims were 2-fold: first, to assess the interobserver reliability among experts, and second to better define salivary gland abnormalities. 28 scanned images of parotid and submandibular glands were scored. In order to appreciate in everyday practice how the differents sonographers scored, we suggested a simplified scoring as: - Identify the echogeneicity of the parenchyma according to the thyroid parenchyma. - Evaluate the homogeneity of the parenchyma in 3 grades: Grade 0: normal parenchyma, Grade 1: mild heterogeneity, grade 2: severe heterogeneity. We didn’t assess the glands size neither the vascularisation because few of the experts use it. Data were analysed using SPSS v15.0 (SPSS Inc., Chicago, IL, USA). Interobserver agreement was estimated using the Cohen’s kappa. Coefficient. Agreement among criteria and considered as follows: excellent ≥ 0.80; good, 0.60-0.79; moderate, 0.40-0.59; and poor, < 0.40 Results Concerning echogenicity the mean kappa was low: 0.3 (0.12-0.8). For homogenicity the mean kappa were respectively: 0.6 (range:0.4-0.8) ; 0.4 (range: -0.1-0.7) and 0.6 (range : 0.5-0.9) for grade 1, 2 and 3. The low agreement for echogeneicity could be due to the evaluation of static images. New definition of each abnormality was elaborated by the experts. In the absence of previous training session a relative good agreement was found between ultrasonographers. Grade 3 is related to the diagnosis of pSS. Conclusions In the absence of well defined consensus, ultrasonography has an acceptable agreement for homogenicity of the parenchyma but not for echogenicity. However, the homogenicity ccomponent is of true diagnostic value in pSS. Training sessions are required and further studies will assess the scoring system and the value of US in clinical trials fro pSS. References De Vita S, Lorenzon G, Rossi G et al. Clin Exp Rhumatol, 1992,10 (4):351-6 Cornec D, Jousse-Joulin S, Pers JO et al. Arthritis Rheum. 2013 Jan;65(1):216-25 Milic VD, Petrovic RR, Boricic IV et al. J Rheumatol. 2009 Jul; 36(7):1495-500 Luciano N, Baldini C, R Pascale et al. Annals of rheum dis. 2012 June S 3 : 16,302 Theander E et al Annals of rheum dis. 2012 June S 3 : 16,904 Disclosure of Interest: None Declared

The bird cherry-oat aphid (Rhopalosiphum padi L.) is an important pest on cereals causing plant growth reduction without specific leaf symptoms. Breeding of barley (Hordeum vulgare L.) for R. padi resistance shows that there are several resistance genes, reducing aphid growth. To identify candidate sequences for resistance-related genes, we performed microarray analysis of gene expression after aphid infestation in two susceptible and two partially resistant barley genotypes. One of the four lines is a descendant of two of the other genotypes. There were large differences in gene induction between the four lines, indicating substantial variation in response even between closely related genotypes. Genes induced in aphid-infested tissue were mainly related to defence, primary metabolism and signalling. Only 24 genes were induced in all lines, none of them related to oxidative stress or secondary metabolism. Few genes were down-regulated, with none being common to all four lines. There were differences in aphid-induced gene regulation between resistant and susceptible lines. Results from control plants without aphids also revealed differences in constitutive gene expression between the two types of lines. Candidate sequences for induced and constitutive resistance factors have been identified, among them a proteinase inhibitor, a serine/threonine kinase and several thionins.

Aphids such as the bird cherry-oat aphid (Rhopalosiphum padi L.) are serious pests in agriculture worldwide. Partially resistant barley genotypes have been produced in a breeding program for resistance to R. padi. The resistance is manifested as smaller aphids after a certain period of nymphal growth on the test plants. A large number of doubled haploid breeding lines thereby characterized as partially resistant or susceptible to R. padi are available from this breeding program. In the present study a selection of these lines, spanning four generations and 23 genotypes, was used for the evaluation of the constitutive transcript abundance of gene sequences in young barley plants. The genes were selected from an earlier microarray study where they had been identified as being up-regulated by aphids in all four barley genotypes studied or differentially up-regulated or constitutively expressed in the two resistant as compared to the two susceptible barley genotypes. The prediction for constitutive transcript abundance across the selection of genotypes was here confirmed for five out of eight investigated genes. Two of these were, as predicted, expressed at equal levels in all genotypes. Two gene sequences exhibited higher transcript abundance in resistant than in susceptible offspring; one coding for a thionin and another for a proteinase inhibitor. A lipoxygenase gene had higher transcript abundance in the susceptible lines. The study thus gives further support for putative constitutive roles of three genes previously identified as significant in the barley–R. padi interaction.