Open Access Open Badges Research article

Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects

Fernando M Pimentel-Santos123*, Dário Ligeiro4, Mafalda Matos5, Ana F Mourão13, José Costa6, Helena Santos7, Anabela Barcelos8, Fátima Godinho9, Patricia Pinto10, Margarida Cruz11, João E Fonseca1213, Henrique Guedes-Pinto2, Jaime C Branco13, Matthew A Brown14 and Gethin P Thomas14

Author Affiliations

1 CEDOC, Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Campo dos Mártires da Pátria, n° 130, 1169-056 Lisboa, Portugal

2 Instituto de Biotecnologia e Bioengenharia, Centro de Genómica e Biotecnologia, da Universidade de Trás-os-Montes e Alto Douro (IBB/CGB - UTAD), Quinta dos Prados, 5000-262 Vila Real, Portugal

3 Centro Hospitalar Lisboa Ocidental (CHLO), Hospital de Egas Moniz EPE, Rua da Junqueira, n° 126, 1349-019 Lisboa, Portugal

4 Centro de Histocompatibilidade do Sul, Alameda das Linhas de Torres, n° 117, 1769 - 001 Lisboa, Portugal

5 Universidade de Trás-os-Montes e Alto Douro, Quinta dos Prados, 5000-262 Vila Real, Portugal

6 Centro Hospitalar do Alto Minho (CHAM), Hospital Conde de Bertiandos EPE, Largo Conde de Bertiandos, 4990-041 Ponte de Lima, Portugal

7 Instituto Português de Reumatologia (IPR), Rua da Beneficência, n° 7, 1050-034 Lisboa, Portugal

8 Centro Hospitalar Baixo Vouga, Hospital Infante D. Pedro EPE, Avenida Artur Ravara, 3814-501 Aveiro, Portugal

9 Hospital Garcia de Orta EPE, Av. Torrado da Silva, Pragal, 2801-951 Almada, Portugal

10 Centro Hospitalar de Vila Nova de Gaia/Espinho EPE, Rua Dr. Francisco Sá Carneiro, 4400-129 Vila Nova de Gaia, Portugal

11 Centro Hospitalar Oeste Norte, Centro Hospitalar das Caldas da Rainha, Rua Diário de Notícias, 2500-176 Caldas da Rainha, Portugal

12 Unidade de Investigação em Reumatologia, Instituto de Medicina Molecular (IMM), Faculdade de Medicina da Universidade de Lisboa, Edifício Egas Moniz, Av. Professor Egas Moniz, 1649-035 Lisboa, Portugal

13 Centro Hospitalar de Lisboa Norte, Hospital Santa Maria EPE, Av. Professor Egas Moniz, 1649-035 Lisboa, Portugal

14 University of Queensland Diamantina Institute, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia

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Arthritis Research & Therapy 2011, 13:R57  doi:10.1186/ar3309

Published: 7 April 2011



A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort.


A total of 18 active AS patients, classified according to the New York criteria, and 18 gender- and age-matched controls were profiled using Illumina HT-12 whole-genome expression BeadChips which carry cDNAs for 48,000 genes and transcripts. Class comparison analysis identified a number of differentially expressed candidate genes. These candidate genes were then validated in a larger cohort using qPCR-based TaqMan low density arrays (TLDAs).


A total of 239 probes corresponding to 221 genes were identified as being significantly different between patients and controls with a P-value <0.0005 (80% confidence level of false discovery rate). Forty-seven genes were then selected for validation studies, using the TLDAs. Thirteen of these genes were validated in the second patient cohort with 12 downregulated 1.3- to 2-fold and only 1 upregulated (1.6-fold). Among a number of identified genes with well-documented inflammatory roles we also validated genes that might be of great interest to the understanding of AS progression such as SPOCK2 (osteonectin) and EP300, which modulate cartilage and bone metabolism.


We have validated a gene expression signature for AS from whole blood and identified strong candidate genes that may play roles in both the inflammatory and joint destruction aspects of the disease.