Page 13 - Recognizing axial spondyloarthritis - Janneke de Winter

Genetic risk factors account for 80-90% of the susceptibility to AS (36) with human leukocyte antigen (HLA)-B*27, part of the major histocompatibility complex (MHC), accounting for 25% of the overall contribution to AS heritability (37). HLA-B*27 has been known for more than forty years (38) and is until now the only genetic biomarker with diagnostic value, if used in a well-defined setting. Recently, genome-wide association studies (GWAS) identified new genetic loci, both inside and outside the MHC. Although unable to pinpoint specific genes, a study by Sims et al indicated that MHC genes other than HLA-B*27 are associated with axial SpA (39).
Imaging biomarkers
Traditionally, sacroiliitis on X-ray according to the modified New York (mNY) criteria ascertained a diagnosis of AS. Over the last decades, MRI is increasingly used to support an early diagnosis of axial SpA; a development supported by the fact that MRI detects inflammation of the SI joints before radiographic structural damage appears. Furthermore, recent studies showed that readers’ agreement on the presence of radiographic sacroiliitis is at best moderate (40,41) and training of readers does not improve the assessment (42). Despite the superior relevance of MRI of the SI joints (MRI-SI) when compared to plain radiographs in a context of early axial SpA diagnosis, MRI-SI has its limitations: The specificity of MRI-SI for SpA-specific sacroiliitis is not well known and physicians may rely too much on a positive MRI-finding (43).
AIM AND OUTLINE OF THE THESIS
The global aim of the studies described in this thesis was to increase the recognition of axial SpA. Recognition in its two definitions: both acknowledgement and identification of the disease. In Part I, we focus on the recognition of the disease burden of axial SpA, focusing on extra-articular (uveitis, psoriasis, IBD) and peripheral (arthritis, enthesitis, dactylitis) manifestations. In Part II, we aim to improve early recognition of the diagnosis of axial SpA in individuals with back pain by identifying and validating novel biomarkers. These include imaging (sacroiliitis on MRI), antibodies (anti-CD74) and an MHC class I gene (HLA-C*07). In Part III, we intend to recognize the early disease processes by assessing the preclinical phase of axial SpA in a cohort of seemingly healthy first-degree relatives of HLA-B*27 positive AS patients.
In detail, this thesis is organized as follows:
Part I of the thesis focuses on the disease phenotype of axial SpA. Once an SpA patient has back pain, the ASAS criteria classify a patient as axial and not as peripheral SpA, regardless of the burden of peripheral disease. In chapter 2 we aimed to assess whether the current classification of SpA as axial or peripheral SpA according to the ASAS criteria justifies the several disease phenotypes by
GENERAL INTRODUCTION AND OUTLINE
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