Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2014

Open Access 01-12-2014 | Research article

Immune cell transcript modules reveal leukocyte heterogeneity in synovial biopsies of seronegative spondylarthropathy patients

Authors: Robin M Hallett, Tracy Chew

Published in: BMC Musculoskeletal Disorders | Issue 1/2014

Login to get access

Abstract

Background

The objective of this study was to identify leukocyte cell types found within the synovia of patients with seronegative spondylarthropathies (SpA), such as ankylosing spondylitis (AS), using transcription based analyses.

Methods

Leukocyte transcriptional profiles obtained from the NCBI’s gene expression omnibus and prediction analysis of microarrays (PAM) was used to identify 25-gene leukocyte metagenes. Subsequently, transcriptional profiles from murine and clinical models of AS and SpA were interrogated to characterize the local infiltration of leukocytes in SpA synovia.

Results

Analysis of a proteoglycan-induced murine model of AS reveals infiltration of dendritic cells, CD4+ T cells, monocytes, and natural killer cells to the spine. In human SpA and AS patients, transcriptional analysis of synovial biopsies revealed local infiltration of dendritic cells and CD4+ T cells.

Conclusions

We identified leukocyte cell types that infiltrated the synovial of SpA patients. Our results imply a role for dendritic cells and CD4+ T cells in the local inflammation that underlies pathogenesis in patients with SpA.
Appendix
Available only for authorised users
Literature
1.
Reveille JD, Sims AM, Danoy P, Evans DM, Leo P, Pointon JJ, Jin R, Zhou X, Bradbury LA, Appleton LH, Davis JC, Diekman L, Doan T, Dowling A, Duan R, Duncan EL, Farrar C, Hadler J, Harvey D, Karaderi T, Mogg R, Pomeroy E, Pryce K, Taylor J, Savage L, Deloukas P, Kumanduri V, Peltonen L, Ring SM, Australo-Anglo-American Spondyloarthritis Consortium (TASC), et al: Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet. 2010, 42 (2): 123-127. 10.1038/ng.513.CrossRefPubMedPubMedCentral
2.
Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Evans DM, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Wellcome Trust Case Control Consortium, et al: Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet. 2007, 39 (11): 1329-1337. 10.1038/ng.2007.17.CrossRefPubMed
3.
Evans DM, Spencer CC, Pointon JJ, Su Z, Harvey D, Kochan G, Oppermann U, Dilthey A, Pirinen M, Stone MA, Appleton L, Moutsianas L, Leslie S, Wordsworth T, Kenna TJ, Karaderi T, Thomas GP, Ward MM, Weisman MH, Farrar C, Bradbury LA, Danoy P, Inman RD, Maksymowych W, Gladman D, Rahman P, Morgan A, Marzo-Ortega H, Bowness P, Spondyloarthritis Research Consortium of Canada (SPARCC), et al: Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet. 2011, 43 (8): 761-767. 10.1038/ng.873.CrossRefPubMedPubMedCentral
4.
Bal A, Unlu E, Bahar G, Aydog E, Eksioglu E, Yorgancioglu R: Comparison of serum IL-1 beta, sIL-2R, IL-6, and TNF-alpha levels with disease activity parameters in ankylosing spondylitis. Clin Rheumatol. 2007, 26 (2): 211-215.CrossRefPubMed
5.
Shen H, Goodall JC, Hill Gaston JS: Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum. 2009, 60 (6): 1647-1656. 10.1002/art.24568.CrossRefPubMed
6.
Appel H, Wu P, Scheer R, Kedor C, Sawitzki B, Thiel A, Radbruch A, Sieper J, Syrbe U: Synovial and peripheral blood CD4 + FoxP3+ T cells in spondyloarthritis. J Rheumatol. 2011, 38 (11): 2445-2451. 10.3899/jrheum.110377.CrossRefPubMed
7.
Appel H, Maier R, Wu P, Scheer R, Hempfing A, Kayser R, Thiel A, Radbruch A, Loddenkemper C, Sieper J: Analysis of IL-17+ cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response. Arthritis Res Ther. 2011, 13 (3): R95-10.1186/ar3370.CrossRefPubMedPubMedCentral
8.
Bowness P, Ridley A, Shaw J, Chan AT, Wong-Baeza I, Fleming M, Cummings F, McMichael A, Kollnberger S: Th17 Cells Expressing KIR3DL2+ and Responsive to HLA-B27 Homodimers Are Increased in Ankylosing Spondylitis. J Immunol. 2011, 186 (4): 2672-2680. 10.4049/jimmunol.1002653.CrossRefPubMedPubMedCentral
9.
Freemont AJ, Denton J: Disease distribution of synovial fluid mast cells and cytophagocytic mononuclear cells in inflammatory arthritis. Ann Rheum Dis. 1985, 44 (5): 312-315. 10.1136/ard.44.5.312.CrossRefPubMedPubMedCentral
10.
Baek HJ, Zhang L, Jarvis LB, Gaston JSH: Increased IL-4+ CD8+ T cells in peripheral blood and autoreactive CD8+ T cell lines of patients with inflammatory arthritis. Rheumatology (Oxford). 2008, 47 (6): 795-803. 10.1093/rheumatology/ken089.CrossRef
11.
Jandus C, Bioley G, Rivals J-P, Dudler J, Speiser D, Romero P: Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum. 2008, 58 (8): 2307-2317. 10.1002/art.23655.CrossRefPubMed
12.
Jansen DTSL, Hameetman M, van Bergen J, Huizinga TWJ, van der Heijde D, Toes REM, van Gaalen FA: IL-17-producing CD4+ T cells are increased in early, active axial spondyloarthritis including patients without imaging abnormalities. Rheumatology. 2014, 263-272. doi:10.1093/rheumatology/keu382
13.
Kenna TJ, Davidson SI, Duan R, Bradbury LA, McFarlane J, Smith M, Weedon H, Street S, Thomas R, Thomas GP, Brown MA: Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive γ/δ T cells in patients with active ankylosing spondylitis. Arthritis Rheum. 2012, 64 (5): 1420-1429. 10.1002/art.33507.CrossRefPubMed
14.
Haynes KR, Pettit AR, Duan R, Tseng H-W, Glant TT, Brown MA, Thomas GP: Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors. Arthritis Res Ther. 2012, 14 (6): R253-10.1186/ar4096.CrossRefPubMedPubMedCentral
15.
Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, Cooke MP, Walker JR, Hogenesch JB: A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci. 2004, 101 (16): 1-6.CrossRef
16.
Thomas GP, Duan R, Pettit AR, Weedon H, Kaur S, Smith M, Brown MA: Expression profiling in spondyloarthropathy synovial biopsies highlights changes in expression of inflammatory genes in conjunction with tissue remodelling genes. BMC Musculoskelet Disord. 2013, 14 (1): 354-10.1186/1471-2474-14-354.CrossRefPubMedPubMedCentral
17.
Abbas AR, Baldwin D, Ma Y, Ouyang W, Gurney A, Martin F, Fong S, van Lookeren CM, Godowski P, Williams PM, Chan AC, Clark HF: Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data. Genes Immun. 2005, 6 (4): 319-331. 10.1038/sj.gene.6364173.CrossRefPubMed
18.
Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003, 4 (2): 249-264. 10.1093/biostatistics/4.2.249.CrossRefPubMed
19.
Hallett RM, Dvorkin-Gheva A, Bane A, Hassell JA: A gene signature for predicting outcome in patients with basal-like breast cancer. Sci Rep. 2012, 2: 227-CrossRefPubMedPubMedCentral
20.
Hallett RM, Dvorkin A, Gabardo CM, Hassell JA: An algorithm to discover gene signatures with predictive potential. J Exp Clin Cancer Res. 2010, 29 (1): 120-10.1186/1756-9966-29-120.CrossRefPubMedPubMedCentral
21.
Hallett RM, Pond G, Hassell JA: A target based approach identifies genomic predictors of breast cancer patient response to chemotherapy. BMC Med Genomics. 2012, 5 (1): 16-10.1186/1755-8794-5-16.CrossRefPubMedPubMedCentral
22.
Tibshirani R, Hastie T, Narasimhan B, Chu G: Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc Natl Acad Sci U S A. 2002, 99 (10): 6567-6572. 10.1073/pnas.082099299.CrossRefPubMedPubMedCentral
23.
Glant TT, Mikecz K, Arzoumanian A, Poole AR: Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthritis Rheum. 1987, 30 (2): 201-212. 10.1002/art.1780300211.CrossRefPubMed
24.
Campbell EC, Fettke F, Bhat S, Morley KD, Powis SJ: Expression of MHC class I dimers and ERAP1 in an ankylosing spondylitis patient cohort. Immunology. 2011, 133 (3): 379-385. 10.1111/j.1365-2567.2011.03453.x.CrossRefPubMedPubMedCentral
25.
Kundzer AV, Volkova MV, Bogdanos DP, Rödiger S, Schierack P, Generalov I, Nevinsky GA, Roggenbuck D: Deoxyribonuclease activity of polyclonal IgGs: a putative serological marker in patients with spondyloarthritides. Immunol Res. 2013, 56 (2): 457-464.CrossRefPubMed
Metadata
Title
Immune cell transcript modules reveal leukocyte heterogeneity in synovial biopsies of seronegative spondylarthropathy patients
Authors
Robin M Hallett
Tracy Chew
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2014
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-15-446

Other articles of this Issue 1/2014

BMC Musculoskeletal Disorders 1/2014 Go to the issue

Research article

Fractures are increased and bisphosphonate use decreased in individuals with insulin-dependent diabetes: a 10 year cohort study

Research article

Changes and sex differences in patient reported outcomes in rheumatoid factor positive RA–results from a community based study

Study protocol

Reduced knee joint loading with lateral and medial wedge insoles for management of knee osteoarthritis: a protocol for a randomized controlled trial

Research article

Radiological features do not predict failure of two-stage arthroplasty for prosthetic joint infection: a retrospective case–control study

Research article

Acceptability of a ‘guidebook’ for the management of Osteoarthritis: a qualitative study of patient and clinician’s perspectives

Research article

Rheumatology clinicians’ experiences of brief training and implementation of skills to support patient self-management