Page 82 - Recognizing axial spondyloarthritis - Janneke de Winter

CHAPTER FIVE
RESULTS
Anti-CD74 IgG antibodies
To confirm the earlier results (7,8), we first measured the level, prevalence and diagnostic value of anti-CD74 IgG antibodies. In the exploratory cohort, median anti-CD74 IgG antibodies (OD) were higher in AS patients than in healthy controls (0.70 vs. 0.51, p<0.001). ROC curve analysis showed an AUC of 0.70 (95% CI 0.62- 0.79) and resulted in a cut-off of 0.52. Using this cut-off, anti-CD74 IgG antibodies were present in 110 out of 138 AS patients vs. 25 out of 57 healthy controls (79.7% vs. 43.9%, p<0.001).
In the SPACE cohort, median anti-CD74 IgG antibodies (OD) did not differ between axSpA patients and CBP patients (0.50 vs. 0.52, p=0.15). ROC curve analysis showed an AUC of 0.47 (95% CI 0.42-0.51). Using a cut-off of 0.52, anti- CD74 IgG antibodies were present in 127 out of 274 axSpA patients and in 137 out of 286 CBP patients (46.4% vs. 47.9%, p=0.71) resulting in a positive predictive value (PPV) of 48.1%, a negative predictive value (NPV) of 50.3%, a positive likelihood ratio (LR+) 0.97 and a negative likelihood ratio (LR-) of 1.03.
Anti-CD74 IgA antibodies
Because anti-CD74 IgG antibodies did not show diagnostic value in the SPACE cohort, we explored the level, prevalence and diagnostic value of anti-CD74 IgA antibodies, since earlier research showed that total serum IgA is elevated in axSpA (12,16) and that IgA is produced at mucosal surfaces, including the gut which may be inflamed in spondyloarthritis (17).
In the exploratory cohort, median anti-CD74 IgA antibodies (OD) were higher in AS patients than in healthy controls (0.31 vs. 0.20, p<0.001). ROC curve analysis showed an AUC of 0.78 (95% CI 0.82-0.79) and resulted in a cut-off of 0.22 (Figure 1). Using this cut-off, anti-CD74 IgA antibodies were present in 39 of 138 AS patients and in 3 out of 57 healthy controls (28.5% vs. 5.3%, p<0.001
In the SPACE cohort, median anti-CD74 IgA antibodies (U/mL) were higher in axSpA patients than in CBP patients (19.9 vs. 14.0, p<0.001, Figure 1). ROC curve analysis showed an AUC of 0.60 (95% CI 0.55-0.65). Using a cut-off of 18.0 U/mL, anti-CD74 IgA antibodies were positive in 150 of 274 axSpA patients vs. 105 of 284 CBP patients (54.7% vs. 37.0%, p<.001). Having a pre-test probability of 46.2% for axSpA (and thus 53.8% not having axSpA), anti-CD74 IgA testing resulted in a PPV of 58.8%, a NPV of 59.1%, a LR+ of 1.48 and a LR- of 0.72.
Analyses using different definitions of axSpA
As the results of the diagnostic biomarker analysis may depend on the “gold standard” for diagnosis of axSpA, we also tested the median anti-CD74 IgG and IgA levels looking at (1) patients in the SPACE cohort who were diagnosed using a strict definition of axSpA (diagnosed as by a rheumatologist and also according to the Assessment of SpondyloArthritis International Society (ASAS) criteria)
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