scholarly journals HLA Alleles Associated With Risk of Ankylosing Spondylitis and Rheumatoid Arthritis Influence the Gut Microbiome

2019 ◽  
Vol 71 (10) ◽  
pp. 1642-1650 ◽  
Author(s):  
Mark Asquith ◽  
Peter R. Sternes ◽  
Mary‐Ellen Costello ◽  
Lisa Karstens ◽  
Sarah Diamond ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Gut Microbiome ◽  
Hla Alleles

scholarly journals HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome

2019 ◽  
Author(s):  
Mark Asquith ◽  
Peter R. Sternes ◽  
Mary-Ellen Costello ◽  
Lisa Karstens ◽  
Sarah Diamond ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Gut Microbiome ◽  
Marker Gene ◽  
Intestinal Microbiome ◽  
Hla B27 ◽  
Microbial Composition ◽  
Hla Alleles ◽  
Microbiome Composition ◽  
Stool Samples

ABSTRACTObjectivesHLA alleles affect susceptibility to more than 100 diseases, but the mechanisms to account for these genotype-disease associations are largely unknown. HLA-alleles strongly influence predisposition to ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Both AS and RA patients have discrete intestinal and faecal microbiome signatures. Whether these changes are cause or consequence of the diseases themselves is unclear. To distinguish these possibilities, we examine the effect ofHLA-B27andHLA-DRB1RA-risk alleles on the composition of the intestinal microbiome in healthy individuals.Methods568 samples from 6 intestinal sites were collected from 107 otherwise healthy unrelated subjects and stool samples from 696 twin pairs from the TwinsUK cohort. Microbiome profiling was performed using sequencing of the 16S rRNA bacterial marker gene. All patients were genotyped using the Illumina CoreExome SNP microarray, and HLA genotypes were imputed from these data.ResultsAssociation was observed betweenHLA-B27genotype, and RA-riskHLA-DRB1alleles, and overall microbial composition (P=0.0002 and P=0.00001 respectively). These associations were replicated in the TwinsUK cohort stool samples (P=0.023 and P=0.033 respectively).ConclusionsThis study shows that the changes in intestinal microbiome composition seen in AS and RA are at least partially due to effects ofHLA-B27and –DRB1on the gut microbiome. These findings support the hypothesis that HLA alleles operate to cause or increase the risk of these diseases through interaction with the intestinal microbiome, and suggest that therapies targeting the microbiome may be effective in their prevention and/or treatment.

AB1367 Persistency with subcutaneous anti-TNF therapy for treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis patients

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 716.2-716
Author(s):  
N. Tandon ◽  
S. Haas ◽  
H.C. Waters ◽  
W. Olson ◽  
S. Bolge ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis

scholarly journals SAT0589 RISK FOR PSYCHIATRIC HOSPITALIZATION FOLLOWING A RHEUMA-RELATED HOSPITALIZATION: RESULTS FROM A CZECH NATIONWIDE, COHORT STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1253.2-1254
Author(s):  
T. Formánek ◽  
K. Mladá ◽  
M. Husakova
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Ankylosing Spondylitis ◽  
Rheumatic Disease ◽  
Rheumatic Diseases ◽  
Psychiatric Hospitalization ◽  
Population Based ◽  
Index Hospitalization ◽  
Increased Risk ◽  
History Of

Background:Cohort studies using nationwide health registers have shown an increased risk for affective and anxiety disorders in people with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) (1-3). Moreover, a nationwide cohort study demonstrated an increased risk for mental disorders in people with rheumatic diseases (4).Objectives:We aimed to investigate the risk for psychiatric hospitalization following a hospitalization for rheumatic disease.Methods:Using data from the Czech nationwide register of all-cause hospitalizations, we obtained 4 971 individuals hospitalized (index hospitalization) between 2004 and 2012 for rheumatic diseases - RA, spondyloarthritis (including AS, psoriatic arthritis and undifferentiated spondyloarthritis), systemic lupus erythematosus and systemic sclerodermia, with no history of psychiatric and rheuma-related hospitalization in the previous 10 years from the index hospitalization. On these individuals, we randomly matched (on age, gender and year of index hospitalization) controls that were hospitalized in the same time period for a non-rheumatic disease and have no history of psychiatric and rheumatic hospitalization in the last 10 years from their index hospitalization, in the ratio of 1:5. We employed conditional logistic regression for assessing the risk for psychiatric hospitalization in the subsequent 3 years from the index hospitalization. To strengthen our results, we repeated the matching step 100 times and run the analysis on each resulting dataset separately, and pooled the results. The findings are expressed as odds ratios (OR) with 95% confidence intervals (95% CI).Results:We identified an elevated risk for psychiatric (OR = 1.34, 95% CI = 1; 1.78) and for affective disorders (OR = 2.19, 95% CI = 1.17; 4.1) in people hospitalized for rheumatic diseases. We did not find a statistically significant association with organic, psychotic and anxiety disorders.Conclusion:There is an increased risk for experiencing a psychiatric disorder in the period of 3 years after a rheuma-related hospitalization.References:[1]Shen C-C, Hu L-Y, Yang AC, Kuo BI-T, Chiang Y-Y, Tsai S-J. Risk of Psychiatric Disorders following Ankylosing Spondylitis: A Nationwide Population-based Retrospective Cohort Study. The Journal of Rheumatology. 2016;43(3).[2]Park J-S, Jang H-D, Hong J-Y, Park Y-S, Han K, Suh S-W, et al. Impact of ankylosing spondylitis on depression: a nationwide cohort study. Scientific Reports. 2019;9(1):6736.[3]Hsu C-C, Chen S-C, Liu C-J, Lu T, Shen C-C, Hu Y-W, et al. Rheumatoid Arthritis and the Risk of Bipolar Disorder: A Nationwide Population-Based Study. PLOS ONE. 2014;9(9).[4]Sundquist K, Li X, Hemminki K, Sundquist J. Subsequent Risk of Hospitalization for Neuropsychiatric Disorders in Patients With Rheumatic Diseases: A Nationwide Study From Sweden. Archives of General Psychiatry. 2008;65(5):501-7.Acknowledgments:Supported by the project (Ministry of Health Czech Republic) for conceptual development of research organization 00023728 (Institute of Rheumatology).Disclosure of Interests:Tomáš Formánek: None declared, Karolina Mladá: None declared, Marketa Husakova Speakers bureau: Novartis

scholarly journals AB0182 EVALUATION OF THE SOCIO-PROFESSIONAL IMPACT OF ANKYLOSING SPONDYLITIS AND RHEUMATOID ARTHRITIS IN TUNISIA: DATA FROM THE BINAR REGISTRY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1390.2-1391
Author(s):  
H. Hachfi ◽  
N. Ben Chekaya ◽  
D. Khalifa ◽  
M. Brahem ◽  
H. Themri ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Marital Status ◽  
Biological Therapy ◽  
Total Duration ◽  
National Registry ◽  
Inflammatory Rheumatic Diseases ◽  
Physically Active ◽  
Absence From Work ◽  
Professional Impact

Background:Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are disabling and common chronic inflammatory rheumatic diseases.Objectives:The aim of our study was to evaluate the socio-professional impact of RA and AS.Methods:Using the Biological National Registry (BINAR) data, which includes ten tunisian rheumatology centers,we identified patients≥18 years with AS and RA according to the ACR and EULAR 2010 criteria(RA) and ASAS 2009 (AS), receiving biotherapy for less than two years.Results:298 patients were included in the study. The percentage of patients with RA was 58.7 % and those with AS 41.3%. The sex ratio was 0.6. The average age of the onset of the disease was 49.1 years ± 14.1 years [18–79]. For marital status, 72% were married, single (25%), widowed (2.6%) and divorced (0.4%). 22.4% of patients were illiterate, 32.7 % (primary), 28.3% (secondary) and 16.6% had an university level. For the RA population, a high disease activity (DAS28-ESR >5.1) was detected in 36% of patients, an erosive arthritis in 73.1% and 7.2% had a coxitis. In the AS group, an elevate BASDAI (BASDAI≥4) was detected in 56.9% of patients and 39% had coxitis. All patients have received Biological therapy concomitant with corticosteroids (59.1%), methotrexate (42.6%), salazopirine (20.8%) and leflunomide (4.7%). 54% of patients had a comorbidity, of which 1.7% was depression. More than half of our patients (54.3%) were unemployed, 40 % were professionally active, and 5.7% were retired due to the rheumatic condition. Absence from work was observed in 15.1% of cases with a total duration exceeding three months in 55.5% of cases. 37.9 % of patients were physically active: regularly (9.8%), irregularly (28.1%) and (62.1%) were sedentary. For the functional impact, HAQ score was 1.31± 0.7 for RA and BASFI was 5.2 ± 4.8 for AS. The working abandonment is significantly associated to: marital status (p=0.039), low level of education (p=0.04),depression (p<0.001), high activity of AS (p=0.004) and BASFI>4 (p=0,001).Conclusion:RA or AS requiring biotherapy have a high socio-economic impact and are responsible for absenteeism at work and even for early working abandonment. Early therapeutic management and a global assessment are essential in order to improve quality of life and working conditions. Longitudinal studies are needed to assess the effect of biological therapy on the socio-professional impact of these chronic inflammatory rheumatic disease.Disclosure of Interests:None declared

scholarly journals FRI0373 ASSOCIATIONS OF VASCULAR PATHOPHYSIOLOGY AND BONE METABOLISM IN ANTI-TNF- TREATED RHEUMATOID ARTHRITIS AND ANKYLOSING SPONDYLITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 783.2-784
Author(s):  
M. Czókolyová ◽  
K. Gulyás ◽  
Á. Horváth ◽  
E. Végh ◽  
Z. Pethö ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Certolizumab Pegol ◽  
Univariate Analysis ◽  
Inflammatory Rheumatic Diseases ◽  
Ageing Population ◽  
Research Support ◽  
Vascular Markers

Background:Cardiovascular (CV) disease and osteoporosis (OP) have become increasing challenges in the ageing population, even more in patients with inflammatory rheumatic diseases, such as rheumatoid arthritis (RA) and spondyloarthropathies. Both RA and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss, accelerated atherosclerosis, increased CV morbidity and mortality.Objectives:Bone and vascular biomarkers and parameters along with the effect of one-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS.Methods:Fifty-three patients including 36 RA patients treated with etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were assessed by ELISA. Bone density was assessed by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and pulse-wave velocity (PWV) were assessed by ultrasound. The effects of vascular markers on bone and bone effects on vasculature undergone statistical analysis.Results:Serum levels of vascular endothelial growth factor (VEGF), PDGF-BB, angiopoietin 2 (Ang2) and cathepsin K (CathK) decreased, procollagen type 1 N-propeptide (P1NP) and sclerostin (SOST) levels increased, soluble receptor activator nuclear kappa B ligand (sRANKL) and osteoprotegerin (OPG) levels showed no differences. When bone and vascular markers were correlated with each other, at baseline, OPG correlated with Ang2 and adiponectin. SOST correlated positively with ccIMT. DXA L2-4 BMD, DXA L1 BMD and DXA femoral neck (FN) BMD correlated with FMD and CRP. QCT trabecular BMD correlated with ccIMT and PON1. According to the univariate analysis, FMD correlated with OPG, ccIMT correlated with SOST and QCT trabecular BMD. Ang1, Ang2 and PDGF-BB showed correlation with Dickkopf-1 (DKK1). Ang2 also correlated with OPG. As suggested by the multivariate analysis, OPG determined FMD; DKK1 was an independent predictor of Ang1, Ang2 and PDGF-BB. OPG was a predictor of Ang2.Conclusion:In our study of anti-TNF treated RA and AS patients, vascular and bone parameters showed numerous correlations. The therapy was clinically effective, it halted further bone loss over 1 year and reduced the production of angiogenic markers.Acknowledgments:This research was supported by an investigator-initiated research grant from Pfizer.Disclosure of Interests:Monika Czókolyová: None declared, Katalin Gulyás: None declared, Ágnes Horváth: None declared, Edit Végh: None declared, Zsófia Pethö: None declared, Szilvia Szamosi: None declared, Attila Hamar: None declared, Anita Pusztai: None declared, Emese Balogh: None declared, Nóra Bodnár: None declared, Levente Bodoki: None declared, Agnes Szentpetery: None declared, Harjit Pal Bhattoa: None declared, György Kerekes: None declared, Katalin Hodosi: None declared, Andrea Domjan: None declared, Sándor Szántó: None declared, Gabriella Szücs: None declared, Hennie Raterman Grant/research support from: UCB, Consultant of: Abbvie, Amgen, Bristol-Myers Sqibb, Cellgene and Sanofi Genzyme, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Zoltán Szekanecz Grant/research support from: Pfizer, UCB, Consultant of: Sanofi, MSD, Abbvie, Pfizer, Roche, Novertis, Lilly, Gedeon Richter, Amgen

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