Background/Purpose: Axial spondyloarthritis (axSpA) is still frequently diagnosed late and its pathogenesis is still unclear. Although a strong genetic association of axSpA with HLA-B27 is known, the gene prevalence varies among different world regions, and its value for the identification of patients with axSpA has been questioned. IgG and IgA antibodies against CD74 have shown good sensitivity and specificity and higher positive likelihood ratio (LR+) for axSpA as compared to HLA-B27. In this prospective study, we tested the performance of IgG and IgA anti-CD74 as early diagnostic marker for axSpA as compared to HLA-B27 in Lebanon, which is known as one of the countries with the lowest HLA-B27 prevalence ever reported.

Methods: Sera of axSpA patients and healthy blood donors (HBD) were analyzed for HLA-B27 genes by PCR and for IgG and IgA anti-CD74 by ELISA. The laboratory workers were blinded for clinical data during the analyses. Patients and HBD were recruited after an advertising program among rheumatologists and primary care physicians across Lebanon. Clinical assessment and sera sample collection were performed at a center specialized in axSpA (University center, Hotel-Dieu de France, Beirut). Inclusion criteria were age 18-45 years, Lebanese nationality, symptom duration <3 years, classification to axSpA (ASAS criteria, imaging arm), no prior exposure to biologics. Interpretation of the radiographic images for inclusion in the study was performed centrally and independent of the recruiting rheumatologist. Clinical and laboratory assessments were performed in all axSpA patients. Comparison between groups was performed with the Mann-Whitney U test. For the diagnostic properties of HLA-B27 and anti-CD74 IgGs, ROC curves were calculated.

Results: Sera of 26 axSpA patients and 69 HBD were collected prospectively. AxSpA patients were slightly older than HBD (31.6 and 27.3 years, respectively, p=0.04) with no other demographic differences. Mean symptom duration was 36.4 months (SD 16.5), mean BASDAI 4.2 (SD 2.0) and mean ASDAS 3.2 (SD 1.2). A total of 14 patients (54%) were classified as nr-axSpA. HLA-B27 status was positive in 9/26 axSpA patients (34.6%) but in no HBD (Sensitivity 34.6%, Specificity 100%). In the ROC analysis, IgG4 anti-CD74 showed the best diagnostic value for axSpA (AUC 0.939, cut-off value 0.55). Using this cut-off, positive values of IgG anti-CD74 were found in 24/36 axSpA patients (66.7%) and 5/69 HBD (7.2%) (Sensitivity and Specificity 92.3%, positive predictive value 82.7%, negative predictive value 96.8%, LR+ 12.0, LR- 0.08).

Conclusion: In this first study in a population with low HLA-B27 prevalence, IgG anti-CD74 antibodies showed higher diagnostic value than HLA-B27 for AxSpA. This is of special interest in populations with low HLA-B27 prevalence, especially on the background of diagnosing axSpA when using the clinical arm of the ASAS classification criteria.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/diagnostic-value-of-anti-cd74-antibodies-in-axial-spondyloarthritis-results-from-a-population-with-low-hla-b27-prevalence-background/