Page 87 - Recognizing axial spondyloarthritis - Janneke de Winter

ANTI-CD74 ANTIBODIES IN EARLY AXIAL SPA
higher in our study than in the previous reports. This may be due either to the fact that the antibodies are higher in CBP patients than in healthy individuals, or may be explained by the fact that the anti-CD74 IgG assay has been modified over time. Indeed, the original assay was sensitive to interference by soluble CD74 in the sera, leading to false negative results in samples where sCD74 had not been degraded by freezing-thawing. In contrast, the assay used here is not biased by the presence of sCD74 and should therefore be more reliable.
In contrast with the previous suggestion that anti-CD74 IgG presence was especially high in early axSpA and declined with longer disease duration (7,8), disease duration did not correlate with anti-CD74 IgG but we noted a lower presence in non-radiographic axSpA as well as a higher presence in CBP controls. Collectively, these data indicate that anti-CD74 IgG has no significant diagnostic value in patients under 45 years presenting with recent onset back pain.
A second important finding of this study is that anti-CD74 IgA appear to perform better that anti-CD74 IgG antibodies as biomarker in axSpA. In contrast to IgG, the anti-CD74 IgA antibody levels were indeed higher in axSpA patients than in CBP patients. Another study investigating the sensitivity and specificity of anti-CD74 antibodies in a cohort of axSpA patients (the InterSpA cohort) vs. healthy donors showed that anti-CD74 IgA antibodies were elevated in 65.4% of 104 patients fulfilling the ASAS axSpA criteria (18). When we used the same cut-off as was used in the InterSpA cohort (15 U/mL), 63.1% of the SPACE axSpA patients had elevated anti-CD74 IgA antibodies. However, also 47.5% of the CBP patients had elevated anti-CD74 IgA antibodies when using this cut-off. Despite the numerical differences in the SPACE cohort between axSpA and CBP patients, testing for anti-CD74 IgA antibodies only modestly increased the pre-test probability of axSpA (46.2%) to 58.8% post-test probability. Similarly, the NPV of anti-CD74 IgA antibodies was low. The LR+ of 1.48 and LR- of 0.72 confirmed that although anti- CD74 is associated with axSpA, their practical significance in diagnostic testing is low. Moreover, the association between axSpA and anti-CD74 IgA antibodies in early back pain may partly be explained by total IgA levels, which have previously shown to be elevated in axSpA patients (12,13). In the SPACE cohort, total IgA was significantly correlated to CRP and ESR levels (data not shown), showing that IgA levels might be linked to the level of inflammation, which is in line with previous research (19,20). In a multivariate analysis, the value of anti-CD74 IgA disappeared when adding total IgA levels.
The strengths of our study include the fact that the SPACE cohort is a well- validated ‘real life’, multicenter, multinational cohort with large numbers of patients. The entry criteria of SPACE were designed to reflect at best the clinical practice of patients presenting with chronic back pain to a rheumatologist and in which the rheumatologist considers the possibility of axSpA in his/her differential diagnosis. The work-up of these patients in the SPACE cohort is very similar to what one would do in clinical practice. As such, almost all patients considered as axSpA in SPACE (and as indicated in Table 2, we used not only clinical diagnosis
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