Page 128 - Recognizing axial spondyloarthritis - Janneke de Winter

CHAPTER SEVEN
questions that we are currently assessing by meticulous follow-up of these first- degree relatives.
Another intriguing finding was that 9 of 17 first-degree relatives (53%) fulfilling SpA classification criteria were HLA–B27 negative, 1 of whom fulfilled both the ASAS axial SpA and ESSG classification criteria, 4 of whom fulfilled the ASAS axial SpA classification criteria, and 4 of whom fulfilled the ESSG classification criteria. This proportion is higher than those previously reported for first-degree relatives (14–43%) with AS and non-radiographic axial SpA (40,41,45), which indicated a lower risk of disease in HLA–B27–negative first-degree relatives. This could be due to the relative size of the current study. However, if this finding is confirmed in a larger sample set, further follow-up of these first- degree relatives will allow us to determine whether those who show signs and symptoms of SpA will develop more active and severe disease, independent of HLA– B27 status, or, alternatively, whether the presence of HLA–B27 promotes exacerbation and persistence of subclinical pathology. Moreover, we could determine whether genetic factors such as single-nucleotide polymorphisms in endoplasmic reticulum aminopeptidase 1 and interleukin-23 receptor contribute more to the development of SpA than previously thought.
In conclusion, the data from this cohort suggest that a substantial proportion of 18–40-year-old first-degree relatives of HLA–B27–positive AS patients do have clinical signs and symptoms and/or imaging abnormalities suggestive of SpA. Indeed, 33% could already be classified as having SpA. Extension of the sample size and follow-up of all subjects will allow us to disentangle the sequence of events that may lead to clinically manifest SpA and will allow us to determine which initial features may predict such a development.
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