Anti-CD74 IgA antibodies show diagnostic potential for axial spondyloarthritis but are not associated with microscopic gut inflammation

Abstract

Objectives Gut inflammation commonly occurs in axial spondyloarthritis (axSpA), and is linked to disease activity and outcome. Given the role of IgA in mucosal immunity, we explored the association between anti-CD74 IgA antibodies, gut inflammation and axSpA. Methods Anti-CD74 IgA was measured by ELISA in serum samples of axSpA patients (fulfilling the 2009 ASAS classification criteria). A group of fibromyalgia (FM) and rheumatoid arthritis (RA) patients served as non-inflammatory and inflammatory controls. Newly diagnosed axSpA patients underwent ileocolonoscopy; mucosal biopsies were histopathologically assessed as normal, acute or chronically inflamed. Optimal anti-CD74 IgA cut-off values were determined with a receiver operating characteristics (ROC) curve. Results AxSpA patients (n = 281) showed higher anti-CD74 IgA levels (mean±SD 18.8 ± 12.4 U/ml) compared with 100 FM patients (10.9 ± 5.0 U/ml, p< 0.001) and 34 RA patients (13.7 ± 9.6 U/ml, p= 0.02). The area under the ROC curve (AUC) for diagnosis (axSpA vs FM) was 0.70, providing a sensitivity of 60% and specificity of 87% (cut-off 15 U/ml). Antibody concentrations were not significantly different between axSpA patients with (n = 40) and without (n = 69) gut inflammation (p= 0.83), yielding an AUC of 0.51. Anti-CD74 IgA levels were not associated with degree of bone marrow oedema on MRI of the sacroiliac joints, CRP, or any other disease-specific feature such as the use of NSAIDs or biological treatment. Conclusion Serum anti-CD74 IgA is a potentially useful diagnostic biomarker for axSpA. However, antibody levels do not correlate with any phenotypical feature, including microscopic gut inflammation, suggesting this to be a disease-specific rather than an inflammatory marker.

Antibodies of the immunoglobulin a isotype to novel antigens in early axial spondyloarthritis

“…Lastly, one of the best described autoantibody biomarkers for axSpA are IgA isotype antibodies against the MHC class II histocompatibility antigen invariant (gamma) chain, also known as CD74 (16), which has been confirmed in different studies. De Winter et al reported on a sensitivity of 55% in early axSpA patients and a corresponding specificity of 63% in persons with chronic back pain (17), which was in line with the recently reported sensitivity of 60% in the BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant) (18), whereas Riechers et al reported a sensitivity of 47% in patients with non-radiographic axSpA (19). Additionally, IgA antibodies against CD74 were found to be associated with structural damage in the sacroiliac joints and the spine of axSpA patients in the ENRADAS study cohort (20).…”

“…Within our study, these IgA antibodies do not seem to allow the identification of a particular subtype of axSpA patients, such as those with IBD. Similarly, in the study of De Winter et al no clinical correlation between IgA anti-CD74 antibodies and IBD could be detected (17), and no correlation between the presence of IgA anti-CD74 antibodies and microscopic gut inflammation could be established in the Belgian (Be)Giant cohort of early axSpA patients (18). Furthermore, the presence of IgA antibodies against several microbial pathogens has not been correlated with a particular axSpA clinical phenotype.…”

“…Additionally, IgA antibodies against CD74 were found to be associated with structural damage in the sacroiliac joints and the spine of axSpA patients in the ENRADAS study cohort ( 20 ). On the other hand, no association between such antibodies and microscopic gut inflammation was found in the Be-Giant cohort ( 18 ).…”