Sensitivity and Specificity of Autoantibodies Against <scp>CD</scp>74 in Nonradiographic Axial Spondyloarthritis

Riechers, E.; Baerlecken, N.T.; Baraliakos, Xenofon; Bakhsh, Katrin Achilles-Mehr; Aries, Peer; Bannert, Bettina; Becker, Klaus; Brandt‐Jürgens, Jan; Braun, Jürgen; Ehrenstein, Boris; Euler, Hans‐Hartwig; Fleck, Martin; Hein, Reinhard; Karberg, Kirsten; Köhler, Lars; Tenbusch, Matthias; Max, Regina; Melzer, Adelheid; Meyer-Olson, Dirk; Rech, Jürgen; Rockwitz, Karin; Rudwaleit, Martín; Schmidt, Reinhold; Schweikhard, Eva; Sieper, Joachim; Stille, C.; Hinüber, Ulrich von; Wagener, P.; Weidemann, Heike-Franziska; Zinke, Silke; Witte, Torsten

doi:10.1002/art.40777

Cited by 32 publications

(26 citation statements)

References 21 publications

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“…The high added value of this combination is mostly due to the identification of IgG4 anti-CD74 in 88% of HLA-B27 negative patients. As in previous studies (23), anti-CD74 were not correlated with HLA-B27, which highlights the diagnostic value of this new marker, and may provide additional clues for a different pathogenic pathway.…”

Section: Discussionsupporting

confidence: 74%

“…DNA of axSpA patients and BD were analyzed centrally for HLA-B27 genes (Polymerase Chain Reaction), without subtype analysis, and sera for IgA and IgG4 antibodies against CD74 by ELISA with specificity for CLIP (Class II-associated invariant chain peptide domain of the CD74 protein consisting of 25 amino-acids) developed in cooperation with AESKU Diagnostics, Germany. The details of testing are described elsewhere (23). All data was anonymized at the local laboratory by attributing a number to each subject upon blood withdrawal and the central laboratory workers were completely blinded for clinical data.…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, 76.4% of patients were HLA-B27 positive. This association was recently studied in European patients with inflammatory back pain of ≤ 2 years duration and clinical suspicion of axSpA and found a sensitivity of Immunoglobulin A (Ig A) anti-CD74 of 47%, a specificity of 95.3% and a LR+ of 10.0 (International SpondyloArthritis autoantibody trial -InterSpA-) (23). The combination of anti-CD74 and HLA-B27 was particularly interesting, with a post-test probability of 80.2% [assuming a 5% pre-test probability of axSpA in CBP (24, 25)], while being of 33.3% for IgA anti-CD74 alone and 28.8% for HLA-B27 alone.…”

Section: Introductionmentioning

confidence: 99%

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Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence

et al. 2019

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Axial spondyloarthritis (axSpA) is often diagnosed late due to the non-specific nature of its main symptom [chronic back pain (CBP)] and to the paucity of diagnostic markers, particularly in regions with low HLA-B27 prevalence, such as the Middle-East. We tested the performance of IgG4 and IgA anti-CD74 antibodies as an early diagnostic marker for axSpA, compared with the performance of HLA-B27, in Lebanon. Sera of axSpA patients diagnosed by the rheumatologist and also fulfilling the imaging arm of the ASAS criteria (patients) and of blood donors (BD) (controls) were analyzed for HLA-B27, IgG4 and IgA anti-CD74, blinded to clinical characteristics. Receiver Operating Characteristic curves were constructed to identify an optimal cut-off point for anti-CD74 antibodies. Diagnostic properties were calculated (sensitivity, specificity, positive, and positive predictive values (PPV, NPV), Likelihood ratios) for each marker. Forty-nine axSpA patients and 102 BD were included in the final analysis. IgA anti-CD74 correlated poorly with axSpA (Area Under the Curve (AUC) 0.657), whereas IgG4 anti-CD74 had a good discriminative value (AUC 0.837). Respectively, for HLA-B27, IgG4 anti-CD74, and the combination of both, we found a sensitivity of 33-92-33%, specificity of 96-79-98%, PPV 80-68-89%, NPV 75-95-75%, and LR+ 8.2-4.4-16.5. IgG4 anti-CD 74 were positive in 88% of HLA-B27 negative axSpA patients, and correlated with BASDAI. In this first study in a population with low HLA-B27 prevalence, IgG4 anti-CD74 antibodies combined with HLA-B27 showed higher diagnostic value than HLA-B27 alone for early axSpA. IgG4 anti-CD74 should be considered for further evaluation as an early axSpA diagnostic marker in future dedicated research, particularly in patients with CBP.

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Section: Discussionsupporting

confidence: 74%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence

et al. 2019

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“…In the first study of 100 patients with non-radiographic axSpA and symptom duration of <2 years 47% had anti-IgA and 17% had anti-IgG antibodies to CD74 as compared to 4.7% of non-SpA back pain controls, respectively (8). In a second study of patients with early axSpA ( n = 274) and with non-SpA chronic back pain (CBP) ( n = 319), 46.4% of axSpA patients and 47.9% of CBP controls had IgG antibodies to CD74 while 54.7% of axSpA patients and 37% of CBP controls had IgA antibodies to CD74 (9). This resulted in a PPV of 58.8% and an NPV of 59.1% for IgA anti-CD74, which is of insufficient diagnostic value in patients with early axSpA.…”

Section: Diagnostic Biomarkersmentioning

confidence: 99%

Biomarkers for Diagnosis of Axial Spondyloarthritis, Disease Activity, Prognosis, and Prediction of Response to Therapy

Maksymowych

2019

Front. Immunol.

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There exists a major unmet need for biomarkers that can identify axial spondyloarthritis (axSpA) early after disease onset because of the availability of highly effective therapies. Several recent reports have examined the autoantibody response in patients with axSpA through the use of protein microarrays and protein-protein interactions although diagnostic performance of biomarkers identified to date has been inadequate. An example of such a biomarker is protein phosphatase magnesium-dependent 1A. Antibodies to the human leukocyte antigen class II-associated invariant chain peptide (anti-CD74) are candidate diagnostic biomarkers but sensitivity declines with increasing duration of disease. Metabolomic studies have employed nuclear magnetic resonance (NMR) spectrometry to identify disease-specific metabolites related to fat metabolism and intestinal microbial metabolism. A second major unmet need exists for biomarkers of disease activity that have superiority over standard C-reactive protein assessment and reflect MRI inflammation in the axial spine. Several biomarkers reflecting inflammation (calprotectin), angiogenesis (vasoactive endothelial growth factor), and connective tissue turnover (C2M, C3M, and citrullinated metalloproteinase degraded fragment of vimentin) have recently been shown to reflect disease activity when compared with clinical outcomes but comparisons with MRI inflammation are very limited. With increasing availability of highly effective but costly therapies, a third unmet need is biomarkers that can predict response to therapies with different mechanisms of action and are superior to C-reactive protein. Calprotectin is currently the only candidate. Although there are as yet no proven therapies for preventing progression of disease there is an unmet need for biomarkers of prognosis that are more responsive than radiography. Aside from CRP no consistent candidates have emerged. Future studies will need to be prospective, include consecutive patients presenting with undiagnosed back pain, and use more reliable and objective endpoints such as MRI inflammation. Moreover, it has become evident that targeted biomarker studies have not been successful in identifying clinically useful biomarkers and technologies that can simultaneously assess “multiomic” markers will need to be analyzed for future advances. These include more sophisticated metabolomic profiling and universal metabolome-standard (UMS) methodology, next generation RNA sequencing, and affinity-based quantitative proteomics based on the use of nucleic acid binders such as the aptamer-based SOMAscan assay.

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“…Antibodies against CD74 were reported to be increased in SpA, and specifically in axial SpA . However, the initial enthusiasm appears to have decreased, with subsequent studies showing negative or less robust results . These differences could be related to the duration of disease, specificity for axial SpA among patients with back pain, or technical issues with the assay, including the use of a small peptide (CLIP) or the entire CD74 protein for the assay, duration of serum storage, and relative CD74–anti‐CD74 binding.…”

mentioning

confidence: 99%

Thinking Positive in Spondyloarthritis

Haroon

2019

Arthritis & Rheumatology

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Sensitivity and Specificity of Autoantibodies Against CD74 in Nonradiographic Axial Spondyloarthritis

Cited by 32 publications

References 21 publications

Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence

Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence

Biomarkers for Diagnosis of Axial Spondyloarthritis, Disease Activity, Prognosis, and Prediction of Response to Therapy

Thinking Positive in Spondyloarthritis

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