EULAR 2019 Meeting in Madrid, Spain
Two Abstracts were accepted from ImmunoCure at EULAR 2019 Meeting in Madrid, Spain.
Abstract AB1101 is about the small subset of Rheumatoid arthritis patients in whom steroids cannot be withdrawn – an interesting rheumatologic dilemma. We showed that these patients have high frequency of Mi2 and Ku antibodies and are in fact Overlap syndromes.
Abstract AB0016 identifies new genes for Psoriasis using Dr. Saeed’s GWAS analytic method, OASIS, in combination with gene expression analysis.
AB1101 (2019)
ANA SUBSETS ANTIBODY PROFILE OF EARLY UNDIFFERENTIATED ARTHRITIS (UA) IN PAKISTAN
Syed Hussain Azhar Rizvi, Tariq Gazdar1, Aneela Pasha, Mohammad Saeed
ImmunoCure, Karachi, Pakistan
Background: Undifferentiated Arthritis (UA) is a group of inflammatory disorders where early synovitis (duration less than 12 months) is present, however patients do not meet criteria for established rheumatologic disorders such as Rheumatoid arthritis, Lupus or Spondyloarthritis (1). On long term follow up, a subpopulation of UA patients converge into definitive Rheumatologic disorders. Up to 50% of early arthritis in European cohorts has been reported to be UA (1, 2).
Objectives: Identify Anti-nuclear antibody (ANA) Subset antibodies in patients presenting with early UA.
Methods: Over a 1-year period (2017-18) patients with early UA were prospectively evaluated. This included clinical exam, routine laboratory investigations including ESR and CRP, RF and anti-CCP as well as Musculoskeletal ultrasound (MSKUS) (3). These patients underwent further testing for ANA Subset antibodies. ANA subsets (17 antibodies) were performed using standard immunoblot assays (EUROIMMUN) at our clinical laboratory (4).
Results: 110 UA patients were found to have positive ANA subsets. The most frequent antibodies were Ku (77.3%) and Mi2 (73.6%) followed by dsDNA (30%) and Nucleosome antibody (29%) ( Figure 1 ). Low frequency antibodies included Sm (n=1), Ribosomal-P and PCNA (n=2 each), Jo-1 (n=3), PM-Scl100 (n=4) and SSB (n=5), whereas Scl70 antibodies were absent. SSA (n=9) and Ro-52 (n=14) together constituted 21% frequency. These antibodies had high signal intensities (mean ± SD SSA = 52±35 and Ro-52 = 46±25). Ku (17±11) and Mi2 (22±15) had modest signal intensities ( Figure 2 ). Clinically 42 patients were classified as RA (RF+ = 33%; anti-CCP+ = 14%) and 41 patients met ACR criteria for SLE while 2 patients met criteria for both and were classified as Rhupus. ANA subset antibody frequencies did not statistically differ between the RA and SLE groups signifying that the clinically classified RA patients in fact had early Rhupus which did not meet ACR criteria for SLE.
Conclusion: Early UA is difficult to categorize clinically, sometimes even after long term follow up, though a substantial portion converge into RA. This study shows that there is a significant portion of early Rhupus in the RA group whose steroid discontinuation leads to a disease flare. ANA Subset antibody profile in such patients may help in their more accurate diagnoses and treatment.
REFERENCES:
[1] van Aken J, van Bilsen JH, Allaart CF, Huizinga TW, Breedveld FC. The Leiden Early Arthritis Clinic. Clin Exp Rheumatol. 2003 Sep-Oct;21(5 Suppl 31):S100-5. PMID: 14969059. [2] Hülsemann JL, Zeidler H. Undifferentiated arthritis in an early synovitis out-patient clinic. Clin Exp Rheumatol. 1995 Jan-Feb;13(1):37-43. PubMed PMID: 7774101. [3] Horton SC, Tan AL, Wakefield RJ, Freeston JE, Buch MH, Emery P. Ultrasound-detectable grey scale synovitis predicts future fulfilment of the 2010 ACR/EULAR RA classification criteria in patients with new-onset undifferentiated arthritis. RMD Open. 2017;3(1):e000394. PMID: 28469936. [4] Op De Beéck K, Vermeersch P, Verschueren P, Westhovens R, Mariën G, Blockmans D, Bossuyt X. Antinuclear antibody detection by automated multiplex immunoassay in untreated patients at the time of diagnosis. Autoimmun Rev. 2012;12(2):137-43. PMID: 22387973.5.ANA Subsets Antibody Frequency
ANA Subsets Antibody Intensity
Disclosure of Interests: Syed Hussain Azhar Rizvi Grant/research support from: Participation in EULAR 2019 Meeting is sponsored by Searle Pak, Tariq Gazdar Shareholder of: Partner at ImmunoCure which performs Autoimmune Disease testing, Aneela Pasha: None declared, Mohammad Saeed Shareholder of: Partner at ImmunoCure – laboratory, which performs Autoimmune antibody testing, Grant/research support from: Participation in EULAR 2019 Meeting is sponsored by High-Q Pharma Pak
Citation: Ann Rheum Dis, volume 78, supplement 2, year 2019, page A2014
Session: Other orphan diseases (Scientific Abstracts)
DOI: http://dx.doi.org/10.1136/annrheumdis-2019-eular.126
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AB0016 (2019)
COMBINED GENOME-WIDE ASSOCIATION AND GENE-EXPRESSION META-ANALYSIS IDENTIFIES NOVEL PSORIASIS GENES
Mohammad Saeed
ImmunoCure, Karachi, Pakistan
Background: Psoriasis (Ps) is a common, inflammatory disorder affecting skin, joints and associated connective tissue, with significant genetic underpinnings. Multiple genome-wide association studies (GWAS) have been conducted with identification of several Ps loci. However, these only explain about a third of Ps genetic risk indicating that additional loci of modest effect remain to be discovered (1).
Objectives: Identify novel psoriasis genes that have functional consequences for psoriasis by altered gene-expression
Methods: Association clustering methods such as gene- and locus-based tests are more powerful than single variant analysis for identifying modest genetic effects (2, 3). Here, a dbGAP GWAS dataset (4) for Ps (pha002855: 1348 Ps cases and 1368 controls, genotyped for 448K SNPs) was analyzed using the locus-based algorithm, OASIS (3), to identify 13 highly significant loci other than the HLA-C locus. In these loci 50 genes were identified using SNIPPER, which were then subjected to gene expression analysis in three Ps GEO datasets.
Results: This genetic and functional analysis identified a total of 18 genes that were significantly associated and had altered expression in psoriasis skin. The most significant of these were two genes that were two-fold upregulated in Ps, IL12B ( P = 9×10 -11 ) and TTC39B ( P = 3×10 -12 ) and two genes that were repressed <50%, MAML2 ( P = 8×10 -19 ) and EBF1 ( P = 1×10 -12 ). Interestingly, the expression of IL23R remained unaltered. Other genes that were significantly upregulated (1.5 – 2.0 fold) were IL12RB2 , TTC1 and PSMD6 . Genes that were also significantly repressed (0.5 – 0.8 fold) were SERBP1 , ATXN7 , PSIP1 , ZNF385D , SIPA1L1 .
Conclusion: This combined genetic and functional meta-analysis elucidated novel genes, functional networks and pathways for psoriasis. These results will lead to important insights into the immunopathogenesis and treatment of psoriasis.
REFERENCES:
[1] Tsoi LC, Stuart PE, Tian C, et al. Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. Nat Commun. 2017May24;8:15382. PMID: 28537254. [2] Luo L, Peng G, Zhu Y, et al. Genome-wide gene and pathway analysis. Eur J Hum Genet. 2010Sep;18(9):1045-53. PMID: 20442747. [3] Saeed M. Novel linkage disequilibrium clustering algorithm identifies new lupus genes on meta-analysis of GWAS datasets. Immunogenetics. 2017May;69(5):295-302. PMID: 28246883. [4] Nair RP, Duffin KC, Helms C, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 2009Feb;41(2):199-204. PMID: 19169254.Disclosure of Interests: Mohammad Saeed Shareholder of: Partner at ImmunoCure – laboratory, which performs Autoimmune antibody testing, Grant/research support from: Participation in EULAR 2019 Meeting is sponsored by High-Q Pharma Pak
Citation: Ann Rheum Dis, volume 78, supplement 2, year 2019, page A1474
Session: Genomics, genetic basis of disease and antigen presentation (Scientific Abstracts)
DOI: http://dx.doi.org/10.1136/annrheumdis-2019-eular.306
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