R. Valle-Oñate

The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection

Objective: To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA). Methods: All Assessment of SpondyloArthritis international Society (ASAS) members were invited to include consecutively new patients with chronic (⩾3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%. Results: Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having “non-radiographic” axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature (“imaging arm”) or the presence of HLA-B27 plus at least two SpA features (“clinical arm”). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%). Conclusion: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain. Trial registration number: NCT00328068.

The Assessment of SpondyloArthritis international Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general

Objective To evaluate new classification criteria for peripheral spondyloarthritis (SpA) in patients with SpA with peripheral manifestations only. Methods In this Assessment of SpondyloArthritis international Society (ASAS) study, two prespecified sets of criteria were compared against the European Spondylarthropathy Study Group (ESSG) and Amor criteria in newly referred consecutive patients with undiagnosed peripheral arthritis, and/or enthesitis, and/or dactylitis that usually began before 45 years of age. The clinical diagnosis (SpA vs no SpA) made by the ASAS rheumatologist served as reference standard. Results In all, 24 ASAS centres included 266 patients, with a final diagnosis of SpA being made in 66.2%. After adjustments a final set of criteria showed the best balance between sensitivity (77.8%) and specificity (82.9%): arthritis and/or enthesitis and/or dactylitis plus (A) one or more of the following parameters: psoriasis, inflammatory bowel disease, preceding infection, human leucocyte antigen B27, uveitis, sacroiliitis on imaging, or (B) two or more other parameters: arthritis, enthesitis, dactylitis, inflammatory back pain in the past, family history of SpA. The new criteria performed better than modified versions of the ESSG (sensitivity 62.5%, specificity 81.1%) and the Amor criteria (sensitivity 39.8%, specificity 97.8%), particularly regarding sensitivity. In the entire ASAS population of 975 patients the combined use of ASAS criteria for axial SpA and ASAS criteria for peripheral SpA also had a better balance (sensitivity 79.5%, specificity 83.3%) than the modified ESSG (sensitivity 79.1%, specificity 68.8%) and Amor criteria (sensitivity 67.5%, specificity 86.7%), respectively. Conclusions The new ASAS classification criteria for peripheral SpA performed well in patients presenting with peripheral arthritis, enthesitis and/or dactylitis.

Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis–associated haplotypes at 11 loci. Two ankylosing spondylitis–associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1.

Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.

Is the Treatment with Biological or Non-biological DMARDS a Modifier of Periodontal Condition in Patients with Rheumatoid Arthritis?

BACKGROUND AND OBJECTIVE Experimental models suggest the use of different therapy protocols in rheumatoid arthritis (RA) as modulators on periodontal condition. This study evaluated the effects of conventional drug treatment and anti-TNF therapy in patients with RA on microbiological and periodontal condition, establishing the association of markers of periodontal infection with indexes of rheumatic activity. MATERIALS AND METHODS One hundred seventy nine individuals with RA were evaluated (62 with anti-TNF-. and 115 with only DMARDs). The periodontal evaluation included plaque and gingival indexes, bleeding on probing (BOP), clinical attachment loss (CAL), pocket depth (PD) and subgingival plaque samples for microbiological analysis. Rheumatologic evaluations included a clinical examination, rheumatoid factor (RF), antibodies against cyclic-citrullinated peptides (ACPAs), and activity markers (DAS28-ERS), high sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR). RESULTS Anti-TNF-alpha therapy influenced periodontal microbiota with a higher frequency of T. denticola (p=0.01). Methotrexate combined with leflunomide exhibited a higher extension of CAL (p=0.005), and anti-TNF-alpha therapy with methotrexate was associated with a lower extension of CAL (p=0.05). The use of corticosteroids exerted a protective effect on the number of teeth (p=0.027). The type of DMARD affected P. gingivalis, T. forsythia and E. nodatum presence. Elevated ACPAs titers were associated with the presence of red complex periodontal pathogens (p=0.025). Bleeding on probing was associated with elevated CPR levels (p=0.05), and ESR was associated with a greater PD (p=0.044) and presence of red complex (p=0.030). CONCLUSION Different pharmacological treatments for RA affect the clinical condition and subgingival microbiota.

SAT0312 Psoriasis and psoriatic arthritis among natives and mestizos from the andean mountains region of peru

Background Previous epidemiological studies described that both Psoriasis (Ps) and Psoriatic Arthritis (PsA) are diseases with negligible prevalence among Natives from the Andean mountains of Peru. We herein first report the presence of Ps and PsA as well as the clinical status of Peruvian Natives and Mestizos with psoriatic disease. Objectives Our purpose was to describe the most salient demographic and clinical features of Peruvian Natives and Mestizos with Ps and PsA from Juliaca, Puno in the Andean mountains region of Peru. Methods During October 1st 2008 to December 31st 2010 consecutive patients attending the rheumatology clinic at the Hospital III in Juliaca, Puno (Southern Peru) at 3824 meters above sea level were carefully assessed for the presence of PsA satisfying the CASPAR classification criteria. The diagnosis of Ps was confirmed by a dermatologist. Descriptive statistics were used to describe the study population. Results Twelve patients with a mean (SD) age of 49.3 (10.7) years fullfilling CASPAR classification criteria were identified. There were 7 (58%) men and 5 (42%) women. 7 PsA patients were Natives of Quechua Ancestry and 5 Mestizos of European and Quechua mix. The main demographic and clinical features of the two ethnic groups included are summarized in table. At the time of first clinical visit all Natives with PsA had no family history of both Ps and PsA and exhibited an established disease (ranging from 12-72 months), were more likely to have a polyarticular disease, and a more severe disease phenotype evidenced by the presence of radiographic damage than Mestizos with PsA. Methotrexate exposure (dose ranging from 15-20 mg/wk) was almost universal in both Natives and Mestizos as was the absence of exposure to biological agents in spite of radiographic damage. Conclusions We first report Ps and PsA in the absence of a family history among Natives of the Andean Mountains of Peru in whom the CASPAR criteria was successfully applied to classify PsA patients. At the time of first visit PsA among the indigenous appeared to be chronic and more severe as most of these patients had radiographic damage. Disclosure of Interest None Declared

AB0201 Influence of siga on clinical activity markers in spa patients with non-radiographic and peripheral compromise

Background There are previous evidence about inflammatory signs related with the intestinal mucosa in spondyloarthritis patients with seronegative arthritis and them relation with articular inflammatory activity. It is uncertain the role of these serological markers on the inflammatory/clinical activity in patients with SpA Objectives To establish the relationship among activity variables and indices, and soluble markers associated to mucosal associated lymphoid tissue in a group of SpA patients. Methods Patients were selected by rheumatologists with the ESSG criteria. Levels of SIgA, IgA, IgA Chlamydia trachomatis, Shigella spp, Yersinia ssp, Campilobacter ssp and Salmonella ssp, CRP,ESR,HLA-B27,BASDAI,ASDAS-CRP and ASDAS-ESR were determined. A principal components analysis (PCA), Poisson Regression and multiple correspondence analysis were performed to find relationships between clinical and laboratory variables and SIgA. This study was approved for Ethics Committee. Results 46 patients were included (78.2% males with a mean age 34.8±12.3 years). It was reported at least one gastrointestinal sing in 69.2% of patients:abdominal bloating (45%), abdominal pain (43%); all patients showed at least one musculoskeletal symptom, 69.5% enthesitis, 63% inflammatory back pain and 58.6% arthritis, as well as 43.4% previous infection and 47.8% presented HLA-B27.The PCA showed three principal factors which cover a contribution of 82.2% to explain the SIgA variation.The ASDAS-CRP, ASDAS-ESR, BASDAI variables which provide the 47.12%;the regression model shows an inverse association among SIgA and BASDAI (prevalence ratio (PR):0.43, 95% CI:0.26–0.70 p=0.001), ASDAS-CRP (PR:0.72, 95% CI:0.24–0.95 p=0.021) and ASDAS-ESR (PR:0.69, 95% CI:0.39–0.95 p=0.007); however, a risk was demonstrated among BASDAI and Yersinia IgA (PR:1.68 95% CI:1.03–2.74 p=0.036) and between ASDAS-CRP with HLA-B27 (PR:1.62 95% CI:1.18–2.19 p=0.0002). There was a relationship between the absence of clinical activity (ASDAS-CRP, ASDAS-ESR and BASDAI), previous infection, Yersinia IgA with SIgA Q1 (27.8–43.0 ug/mL); the presence of arthritis, Salmonella IgA, and high levels of CRP and ESR were related with SIgA Q2; SIgA levels among (Q3)12.2–18.0 ug/mL were associated with inflammatory back pain, obesity and Salmonella IgA <1/1600. High scores of BASDAI and ASDAS-CRP, absence of previous infection had a strong relation with low levels of SIgA. Conclusions SIgA serum level were the only one serologic maker, which had an inverse correlation with all clinical activity variables of disease, previous infection and some specific antibodies associated with intestinal mucosal infection, suggesting a protective role of this molecular shape of IgA that is characteristic of mucosal immune responses References Mantis NJ. Mucosal Immunol (2011) 4:603–11. Disclosure of Interest None declared

THU0137 Impact of periodontal and rheumatic disease markers on first-degree relatives of patients with rheumatoid arthritis according to age group

Background Rheumatoid arthritis (RA) and periodontal disease (PD) have similar underlying pathologic processes and share a general deregulation of the inflammatory response. Objectives To evaluate PD markers in first-degree relatives (FDR) of consanguinity individuals of patients with rheumatoid arthritis to compared with controls and to establish an association to rheumatic activity according to age groups Methods 201 FDR individuals and 201 matched controls were included. Clinical evaluation of rheumatologic and periodontal condition was performed. P. gingivalis, P. gingivalis IgG1 and IgG2, ESR, CRP, RF, ACPAs, painful and swollen joints were assessed. A frequencies analysis, comparisons and a logistic regression model were made. The study was approved by local ethics committee. Results 37.3% of patients with overweight and 10.1% obsesses. Subjects with more than one swelling joint were 21 subjects <30 years, 5 between 31–40, 5 between 41 to 50 subjects and 9 subjects over 50, for more one painful joint were 73. The RF was present in 8.0%, APCA in 13%, RA33 in 1%. 67.3% had a diagnosis of PD, 81.6% had a moderate-severe p=0.003.P. gingivalis was in 47,9%, and P. gingivalis IgG1 were in 54.7%. It was evidenced that 25.3% patients presented BMI>30, where 81.8% had periodontitis p=0.006. Regression analysis on the whole group shows a risk to present BMI>25 (OR 1.67 IC-95% 1.02 – 2.74 p=0.042), ACPAs (OR 3.7 IC-95% 1.34–10.22 p=0.012), at least one pain join (OR2.51 IC-95% 1.42–4.44 p=0.001) and gingival index (OR4.57 IC-95% 1.76–11.80 p=0.002) in FDR individuals. Based on age the risk to develop PD was increasing: individuals among 30 to 40 years shows OR 2.76 (IC-95% 1.24–6.18, p=0.013); among 41 to 50 years, OR 4.72 (IC-95% 1.81–12.32, p=0.001); and for >50 years individuals an OR 6.22 (IC-95% 2.55–15.1, p=0.0001). The discriminating analysis by age rank shows that FDR individuals <30 years (n=67) exhibited high risk to have at least one pain join (OR 3.84 IC-95% 1.28–11.47 p=0.016). In subjects among 30 to 40 years (n=46), the risk was associated with periodontal pocket (OR1.44 IC-95% 1.05–4.98 p=0.021), one or more pain join (OR 3.56 IC-95% 1.22–10.40 p=0.020) which it was maintained until 50 years individuals (n=35) (OR4.32 IC-95% 1.11–16.78 p=0.0034), individuals >50 years (n=53) show high risk to present BMI>25 (OR 4.00 IC-95% 1.46–10.45 p=0.007). Conclusions Obesity, ACPA and periodontitis can be considered as relevant conditions associated with the development of RA in FDRs. However, the analysis based on age group shows that periodontal markers do not appear early in FDR individuals; however, clinical rheumatologic variables are manifested and maintained over time. References Bello-Gualtero JM et al. J Periodontol 2016;87:346–356. Disclosure of Interest None declared

AB0675 Is The Periodontal Clinical and Microbiological Condition in Spondyloarthritis Similar than Rheumatoid Arthritis

Background The periodontal disease (PD) generates systemic impact given the increase in acute phase reactants related to the inflammatory. The relationship between Rheumatoid arthritis (RA) and PD is supported by pathological and immunological data but is not clear this association in Spondyloarthitis (SpA). The association between their respective disease activities and severities are less documented. Periodontal inflammation may affect disease activity and severity on patients with SpA. Objectives To evaluate the association between clinical indices of PD and markers of disease activity in SpA patients and compare these markers in patients with RA and controls. Methods The rheumatologic condition and periodontal status of 79 individuals with SpA, 59 patients with RA and 79 matched-controls were evaluated. Porphyromona gingivalis (Pg), IgG1, and IgG2 to Pg were determined. The C-reactive protein-, erythrocyte sedimentation rate-, HLA B 27, rheumatoid factor-RF, anti-citrullinated protein antibodies, and disease activity measures for SpA and RA were assessed. The rheumatologic Scores and periodontal condition were evaluated by two experienced and calibrated periodontists and rheumatologist. The groups were compared with Kruskal Wallis, Mann-Whitney U and Wilcoxon tests test and a paired t-test. The chi-square test was used to evaluate periodontal variables and SpA disease activity. The institutional Ethics Committee approved the study. Results 79 SpA patients with the following subtypes were included: Ankylosing Spondylitis (AS) (19), undifferentiated SpA (46), and reactive arthritis (ReA) (14). SpA patients had a considerable frequency of periodontitis (55.7%). Of them, 39.2% were classified as moderate and 2.5% as severe periodontal condition. No differences was found in frequency of periodontal condition between subtypes. SpA patients showed lower levels of insertion loss compared to RA patients and the control group (p<0.05). A significant association was observed in microbiological variables of SpA patients. The frequency of (P gingivalis) in the control group was 51.9% compared to 30% in SpA (p=0.015), especially in those with good response to NSAIDS (p= <0.05). Significant associations between the severity of periodontal involvement in RA patients was observed. 63.8% of RA patients had moderate severity disease (49.2%) and severe periodontitis (13.6%) (p=0.035) but not in SpA group. There were not association between disease activity measures in SpA, periodontal and severity condition. Conclusions As compared to RA and healthy controls, periodontal condition in SpA patients was similar. Lower grades of severity and bacterial load were found. This suggests that an interdisciplinary treatment between periodontists and rheumatologists may help to modulate periodontal condition and prevent systemic impact References Pischon N, Pischon T, Gülmez E, Kröger J, Purucker P, Kleber BM. Periodontal Diseases in Patients with ankylosing spondylitis. Ann Rheum Dis 2010;69:34–38. Białowąs K1, Swierkot J1, Radwan-Oczko M.Role of Porphyromonas gingivalis in rheumatoid arthritis and inflammatory spondyloarthropathies. Postepy Hig Med Dosw. 2014;68:1171–9. Disclosure of Interest None declared

AB0942 Diagnostic Value of Anti-RA33 Antibody in Comparison with Anti-Cyclic Citrullinated Peptide Antibodies and Rheumatoid Factor in Patients with Early Arthritis and Individuals with First-Degree Relatives of Patients with RA

Background Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease characterized by joint involvement, pain and inflammation with or without extra-articular joint commitment. Serological markers can guide early diagnosis before that clinical activity takes place, optimizing early diagnosis, less activity and functional disability. RA 33 is considered a diagnosis-marker in RA patients related to prognosis and therapeutic response compared with conventional markers. RA 33 is common in patients with negative conventional markers and with few clinical symptoms. Objectives Evaluated the frecuency of RA33 in individuals with first-degree relatives of patients with RA and patients diagnosed with early rheumatoid arthritis as a good prognosis marker Methods A transversal study was conducted evaluated rheumatologic and periodontal condition of 112 individuals with first-degree relatives of patients with RA and 46 patients diagnosed with early rheumatoid arthritis, according to classification criteria for RA (ACR-EULAR 2010). In addition, 47 healthy individuals were included. RA patients and control group were matched for age and gender. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor RF, ACPAs, and RA 33 were performed. VAS Pain Scale, SDAI Index, HAQ and DAS28 were evaluated. Porphyromona gingivalis (Pg) by CRP, IgG1, and IgG2 were determined. The data included in the study were analyzed using STATA 11.1. Associations were determined by the statistical test Chi 2, and Comparisons between groups of rheumatologic diagnosis and median values for continuous variables was performed using Mann-Whitney Test. Approved by the Ethics Committee of the Institution. Results 112 healthy individuals with first-degree relatives of patients with RA were assessed. Of them 78.3% has periodontal disease, presence of painful joints (30.63%). 36.94% patients had Pg in subgingival plaque samples. In the control group the presence of periodontal disease was 71.74%, tender joints (19.57%), swollen joints (6.52%). Disease activity measures were not representative. Only a woman in the group of family related RA patients was positive for RA 33 (49 years old, without treatment, painful and swollen joints and the presence of periodontal disease and Pg, ESR and CRP positives but RF and ACPAs negative). No patient with RA of less than two years of diagnosis was positive for RA 33. Conclusions The diagnostic value of anti RA33 was low in this population, with regard of worst prognosis markers and higher disease severity. Ra33 should be more follow-up clinical and paraclinical to subjects with risk factors who could have positive markers, without symptoms. References Fritsch R, Eselböck D.Characterization of Autoreactive T Cells to the Autoantigens Heterogeneous Nuclear Ribonucleoprotein A2 (RA33) and Filaggrin in Patients with Rheumatoid Arthritis. The Journal of Immunology.2002; 169 (2):1068–1076. Massardo L.Artritis reumatoide temprana early rheumatoid arthritis.Rev méd Chile. 2008; 136: 1468–1475 Disclosure of Interest None declared