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Abstract
Background Axial spondyloarthritis (AxSpA) is a severe and potentially debilitating disease, where earlier diagnosis lead to a better prognosis. Although HLA-B27 antigen is strongly associated with AxSpA, this marker may have a low sensitivity in some Middle-Eastern countries. Recent European studies showed a strong association between antibodies against CD74 and AxSpA with a sensitivity of 85.1%, specificity of 92.2%, and positive likelihood ratio (LR) of 10.8. The diagnostic properties of anti-CD74 may have a particular interest in non-European countries with low HLA-B27 such as Lebanon.
Objectives In this prospective study, we tested the diagnostic properties of IgG and IgA anti-CD74 as an early diagnostic marker for AxSpA, compared with 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 (PCR) and for IgG and IgA anti-CD74 (ELISA). The patients were recruited from rheumatology clinics across Lebanon. Clinical assessment and sera sample collection were performed at a center specialized in AxSpA (Hotel-Dieu de France University hospital, Beirut). Inclusion criteria were: age 18–45 years, Lebanese, symptom duration <3 years, AxSpA as per ASAS criteria (imaging arm), no prior biologic therapy. Interpretation of the radiographic images was performed centrally and blindly. Clinical and laboratory assessments of the disease were performed in all AxSpA patients. Comparison between groups was performed with the Fisher exact test and Student's test. For the diagnostic properties of HLA-B27 and anti-CD74, ROC curves were calculated.
Results 29 AxSpA patients and 75 HBD were tested. AxSpA patients were slightly older (31.3 and 27.4 yo, respectively, p=0.02). Male gender was slightly predominant (51.7% and 53.6%, respectively). 93% had all characteristics of IBP as per ASAS criteria. 62.1% had non radiographic AxSpA. Mean disease duration was 25.2 months (SD 15.9), mean BASDAI 4.5 and mean ASDAS 3.25. 58.6% had extra-articular manifestations (28% enthesitis, 24% psoriasis, 21% peripheral arthritis, 10% IBD and 7% uveitis). 27.6% had familial history of SpA (21%), psoriasis (10%) and Crohn's disease (3.4%). HLA-B27 status was positive in 10 AxSpA patients and in 2 HBD (Sensitivity 34.5%, Specificity 97.2%, Positive LR 12.24). In the ROC analysis, IgG4 anti-CD74 showed the best diagnostic properties for AxSpA (AUC 0.939, cut-off value 0.55). Using this cut-off value, positive values of IgG anti-CD74 were found in 27 axSpA patients and 5 HBD (Sensitivity 93.1%, Specificity 93.3%, positive predictive value 84.4%, negative predictive value 97.2%). Positive LR was 13.97. Anti-CD74 was positive in 58.6% HLA-B27 negative AxSpA (Fig1).
Conclusions In this 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.
Disclosure of Interest None declared