We aimed to assess the mRNA expression of MHC class 1-related molecules in ankylosing spondylitis (AS) patients vs healthy controls (HCs) and, subsequently, if the absence of HLA-C*07 is associated with genetic susceptibility to axial spondyloarthritis (axSpA). HLA-C*07 was assessed in (a) an exploratory cohort of 24 AS patients vs 40 HCs, (b) a confirmatory cohort of 113 AS patients and 83 non-radiographic axSpA patients from the GErman SPondyloarthritis Inception Cohort (GESPIC) vs 134,528 German potential stem cell donors, and (c) an early back pain cohort with 94 early axSpA patients vs 216 chronic back pain (CBP) patients from the SPondyloArthritis Caught Early (SPACE) cohort. In the exploratory cohort, 79% of the AS patients were HLA-C*07 negative compared to 35% of the HCs (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-axSpA patients were HLA-C*07 negative. In the SPACE cohort, 70% of the axSpA patients were HLA-C*07 negative compared to 44% of CBP patients (p < 0.0001); the association between HLA-C*07 negativity and a diagnosis of axSpA was independent from HLA-B*27. In conclusion, the absence of HLA-C*07 is associated with genetic susceptibility to axSpA.
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We acknowledge Prof. Martin Rudwaleit and Prof. Joachim Sieper for their role in establishing GESPIC. We thank Junior Lardy, PhD, for his help with HLA typing.
GESPIC has been financially supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung—BMBF). As funding by BMBF was reduced according to schedule in 2005 and stopped in 2007, complementary financial support has been obtained also from Abbott/Abbvie, Amgen, Centocor, Schering-Plough, and Wyeth. Since 2010, GESPIC has been supported by Abbvie. Additional support has been obtained also from ANCYLOSS (grant number FKZ 01EC1002D), ArthroMark (grant numbers FKZ 01EC1009A and FKZ 01EC1401A), and METARTHROS (grant number FKZ 01EC1407A) projects funded by BMBF. DB is supported by a VICI grant from the Netherlands Scientific Organization (NWO), a consolidator grant from the European Research Council (ERC), and a grant from the Dutch Arthritis Foundation (Reumafonds).
Conflict of interest
The authors declare that they have no conflict of interest.
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