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Wei as databank in taiwan 2011
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Wei as databank in taiwan 2011

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Wei as databank in taiwan 2011

Wei as databank in taiwan 2011

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  • Dr Wei, Tsai and Chou published a highly-citated paper showing that HLA-B60 and B61 are strongly associated with B27-negative AS in Taiwan.
  • Dr Wei and colleagues in Chung Shan medical university had set up an AS databank to investigate the association of AS genotype and clinical phenotype. They had found that MMP-3/ TIMP alleles correlate to disease activity and functional index of AS.
  • They also collaborated with Prof Brown in Australia and found that IL1 gene complex was associated with AS in Taiwanese Chinese.
  • Moreover, investigators from Taiwan, China and Prof David Yu in UCLA had close collaboration to discover candidate biomarker for spondyloarthritis by microarray and rt-PCR.
  • They had found RGS1 as candidate biomarker for USpA, as well as NR4A2, IL-8…etc.

Wei as databank in taiwan 2011 Wei as databank in taiwan 2011 Presentation Transcript

  • 台灣僵直性脊椎炎資料庫 Ankylosing Spondylitis Databank Project in Taiwan 魏 正 宗  James Cheng-Chung Wei, M.D., Ph.D.   中山醫學大學附設醫院過敏免疫風濕科主任 Director, Division of Allergy, Immunology & Rheumatology Chung Shan Medical University Hospital, Taichung, Taiwan Chairman, Taiwan AS caring society
  • AS in Taiwan
    • Normal population: 23 M
    • Estimated AS prevalence: 0.2-0.4 %
    • National Health Insurance
    • TNF blockers reimbursed for severe refractory AS
      • BASDAI>6, ESR>28, CRP>1 mg/dl, B27+
    • AS caring society since 1998
  • AS caring society in Taiwan www.ascare.org.tw
  • Ankylosing Spondylitis Databank Project in Taiwan Backgrounds / Aims
    • There are still many unmet needs in the pathogenesis and management of AS.
    • To setup a research collaboration network in Taiwan.
    • A comprehensive AS translational database including clinical parameters and tissue samples is crucial and essential for future researches.
  • Methods
    • Collected since 2003, still ongoing in CSMUH, Taichung, Taiwan.
    • Other cohorts in Taipei and Kaoshiung.
    • All first visit AS patients and some other SpA.
    • Comprehensive 10 pages epidemiological questionnaire
    • Psochometric validation of the Chinese version of Bath indices : Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Index (BAS-G
  • Chinese version of Bath indices Reliability of BASDAI 、 BASFI 、 BAS-G James Cheng-Chung Wei , Ruey-Hong Wong,Jun-Huang Huang, Chen-Tung Yu, Chung-Tei Chou, Ming-Shiou Jan, Gregory J. Tsay, Ming-Chih Chou, Hong-Shen Lee. Clin Rheumatol 2007;26:1685-1691 BASDAI BASFI BAS-G Number of items in Scale 6 10 2 Cronbach’s coefficient Alpha 0.85 0.94 0.91 ICC Test/Retest 0.93 0.92 0.94
  • BASDAI 活性量表 Bath Ankylosing Spondylitis Activity Index James Cheng-Chung Wei, Ruey-Hong, Ming-Chih Chou, Hong-Shen Lee. Clin Rheumatol (2007) 26:1685–1691
  •  
  • BAS-G 整體量表 Bath Ankylosing Spondylitis Patients’ Global Assessment
  • Physical examination
    • Finger to floors
    • Modified Schober test
    • Occipital-to-wall
    • Lateral bending test
    • Shoulder and hip examination
  • AS Tissue Bank in Taiwan
    • Inflammatory markers: Erythrocyte sedimentation rate (ESR) , Hypersensitive C-reactive protein (hs-CRP) and Immunoglobulin A (IgA) .
    • Serum were separated within 2 hours and stocked into -80 degree.
    • Peripheral blood mononuclear cells (PBMC) were separated and stored in liquid nitrogen.
    • DNA and RNA were extracted and stocked into -20 degree refrigerators.
    • HLA-B27 by PCR
    • HLA-B27subtyping by PCR-SSO methods.
    • HLA-ABC typing by lymphocytotoxicity assay.
  • Results Taichung CSMUH Cohort Ankylosing Spondylitis Databank Project in Taiwan
  • Taiwan AS databank
    • 3000+ visits and samples from AS patients, including
      • 1500 first-visit patients
      • 2000+ follow up visits
    • 1500 DNA samples were collected.
    • 130 RNA from peripheral mononuclear cell
    • Some synovial fluid, synovium, enthesis, and bone.
  • CSMUH cohort
    • Mean age was 34.28  11.21
    • Sex ratio (M:F) was 2.82 : 1.
    • Disease duration of 5.10  6.45 years
    • Delay diagnosis time lag was 5.91  6.64 years.
    • 42.59 % patients have known family history
    JC Wei. Ankylosing spondylitis databank in Taiwan , PhD thesis, 2007
  • Bath Indices
    • Average BASDAI was 3.99  2.26,
    • BASFI 2.13  2.17 and
    • BAS-G 4.27  2.82 cm in 10-cm scale.
    • 61% were disease-active ( BASDAI>3 )
    • 27% were functional disabled ( BASFI>2 )
  • Physical examinations Finger to floor distance, > 10 cm (%) (AS, n=820) 499 (60.85) Schober’s test, < 15cm (%) (n=818) 783 (95.72) Chest expansion test, < 5cm (%) (n=815) 532 (65.28) L’t lateral bending test, < 10cm (%) (n=812) 247 (30.42) Occiput to wall distance, > 0 cm (%) (n=814) 143 (17.57) Shoulder pain or limitation of motion (n=779) 197 (25.29)
  • Clinical manifestations Variables Patient number (%) History of the buttock pains and back, no. (%) 755 (93.44) History of peripheral arthritis, no. (%) 518 (64.43) History of uveitis, no. (%) 195 (24.19) History of psoriasis, no. (%) 112 (13.90) History of hematuria no. (%) 55 (6.86) History of oral ulcer, no. (%) (n=805) 94 (11.68) Onset symptom, no. ( peripheral arthristis / enteritis / back pain / uveitis) (%) ( 21.55 /2.96/50.56/2.54) HLA-B27 positive 91.2 % Family history of spondyloarthritis 349 (43.35)
  • HS-CRP Variable HS-CRP- p value HSCRP- r BASDAI 0.0005 0.15117 BASFI 0.0002 * 0.16228 BAS-G 0.0001 * 0.22709
  • HLA-B27 in Taiwan
    • 91% of AS patients have HLA-B27.
    • 5-9% in whole population in Taiwan
    • HLA-B27 subtyping: 89% B2704 in Taiwan
    2704 2705 2706 2707 Total AS 108 3 0 0 111 Normal 72 4 5 3 84
  •  
  • Annals of the Rheumatic Diseases. 2009;68:1781–1786.
    • Results:
    • MMP-3/TIMP-1 alleles showed that 6A/C (OR = 3.23, 95% CI 1.50 to 6.95) and 6A/T (OR = 2.55, 95% CI 1.17 to 5.54) had a significantly greater risk of AS than the 5A/T alleles.
    • MMP-3/TIMP-1 5A/T alleles had the lowest BASDAI (p = 0.02), BASFI (p = 0.05) and BAS-G (p = 0.02) among all MMP-3/TIMP-1 alleles.
  • SNP vs Phenotype study
  •  
  • SNP of OPG in AS JH Huang, JC Wei. Rheumatology 2010
  •  
  • Arthritis &rheumatism 2009;60(11),3269–79. (J. Gu and JCC Wei and Yu-Ling Wei contributed equally)
  • Identification of RGS1 as a Candidate Biomarker for Undifferentiated Spondylarthritis J. Gu, JCC Wei ,Yu-Ling Wei, D. Yu. Arthritis & rheumatism 2009;60(11),3269–79.
  • Future works
    • More works on genotype and phenothype
    • Micro-RNA studies
    • Registry database for AS patients under TNF blockers therapy
      • Focus on hepatitis B and TB
    • International collaboration
  • Conclusions
    • Our Chinese versions of the BASDAI, BASFI, and BAS-G showed good reliability, validity, and responsiveness .
    • We had established a comprehensive clinical and tissue database of AS in Taiwan.
    • This database can be used for further researches, medical practice and education.
  •  
  • Thank you James Cheng-Chung Wei, M.D., Ph.D. [email_address] +886 975 128095 Chung Shan Medical University Hospital Chinese Medicine Clinical Trial Center