Page 148 - Recognizing axial spondyloarthritis - Janneke de Winter

CHAPTER NINE
who may have nonspecific chronic back pain rather than axial SpA. The only means to avoid over-diagnosis of axial SpA is to act based on thorough knowledge of the clinical syndrome of axial SpA and MRI abnormalities. The finding of this and other recent studies with comparable outcome will hopefully influence the role of MRI in the diagnostic process, where there are two options. 1) MRI of the SI joints should only be considered in patients with a high suspicion of axial SpA, and 2) the threshold for ‘positive MRI of the SI joints highly specific for axSpA’ should be redefined. In other words, either the threshold for testing or the threshold for a positive test should be set higher, in order to gain specificity and avoid false- positives.
HLA-C*07 absence is associated with susceptibility to axial SpA
In Chapter 6, we report the novel finding that absence of HLA-C*07 is associated with axial SpA. We showed a lower prevalence of HLA-C*07 in axial SpA when compared to controls in three different settings: an exploratory cohort of AS patients versus healthy controls (HC), a cohort of patients with full-blown AS versus a large cohort of German donors, and an early back pain cohort (the SPACE cohort) where we compared HLA-C*07 in axial SpA patients with chronic back pain (CBP) patients. In the exploratory cohort, 79% of the AS patients were HLA-C*07 negative compared to 35% of the HC (p<0.001). This difference was confirmed in GESPIC with 73% of AS patients being HLA-C*07 negative compared to 50% of the controls (p<0.0001); 59% of the nr-axial SpA patients were HLA-C*07 negative. In the SPACE cohort, 70% of axial SpA patients were HLA-C*07 negative compared to 44% of CBP patients (p<0.0001). The effect of HLA-C*07 is associated with genetic susceptibility to axial SpA additionally to the effect of HLA-B*27. HLA-C*07 status is possibly linked to an axial SpA phenotype with high inflammation and radiographic damage and with a low psoriasis prevalence.
Although other MHC genes than HLA-B*27 are suggested to be involved in axial SpA susceptibility by genome-wide association studies (GWAS) (35–37), this study reports the first robust HLA association with axial SpA since the discovery of the HLA-B*27 association in 1973 (38). The proposed genetic association of HLA-C*07 with axial SpA could be relevant for several reasons. First, HLA-C*07 might serve as a biomarker facilitating an early axial SpA diagnosis. Second, our data suggest that HLA-C*07 is linked to radiographic progression, and beyond diagnosis, HLA-C*07 could therefore help to stratify axial SpA subpopulations and function as a prognostic marker. Third, this finding could potentially be relevant for pathophysiology. And, forth, this finding could lead to defining new treatment targets in specific subpopulations of patients. Future research in other (larger) cohorts of patients and controls will have to confirm the association of HLA-C*07 absence with axial SpA, investigate the effect of linkage disequilibrium and thus independence of this finding from HLA-B*27 and study the role of HLA-C*07 in axial SpA pathogenesis.
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