Anti-CD74 antibodies in spondyloarthritis: A systematic review and meta-analysis

https://doi.org/10.1016/j.semarthrit.2020.12.002Get rights and content

Highlights

  • The levels of anti-CD74 IgG and IgA antibodies were both significantly increased in spondyloarthritis patients compared with health controls.

  • Anti-CD74 IgG and IgA antibodies had the moderate sensitivity and high specificity of spondyloarthritis diagnosis.

  • Recent studies indicated that anti-CD74 antibodies could potentially act as biomarkers for the diagnosis of spondyloarthritis.

Abstract

Objective

There is still an unmet need for a simple and reliable biomarker for the diagnosis of spondyloarthritis. Recent studies indicated that anti-CD74 antibody could act as a biomarker for spondyloarthritis. Therefore, this review aims to evaluate the levels of anti-CD74 IgG and IgA antibodies in spondyloarthritis and the diagnostic value of anti-CD74 antibodies.

Methods

PubMed, Web of Science and Medline were comprehensively searched from inception to August 7th, 2019. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was used to estimate the differences of the levels of anti-CD74 IgG and IgA antibodies between spondyloarthritis patients and controls. Sensitivity, specificity and summary receiver operating characteristics (SROC) curve were used for evaluating the diagnostic value of anti-CD74 antibodies. The use of fixed-effect or random-effects model depended on heterogeneity.

Results

Among 55 searched studies, 9 studies were finally included for analysis. Anti-CD74 IgG and IgA antibodies were both significantly increased in spondyloarthritis patients compared with matched controls (IgG: SMD = 0.88, 95% CI = 0.55 to 1.21; IgA: SMD = 0.98, 95% CI = 0.68 to 1.28). The pooled sensitivity, specificity and area under the SROC curve of anti-CD74 IgG antibodies were 0.61, 0.90 and 0.8881, while these indicators of anti-CD74 IgA antibodies were 0.59, 0.95 and 0.8671, respectively.

Conclusion

Anti-CD74 IgG and IgA antibodies were significantly increased in spondyloarthritis patients and suggest a high diagnostic specificity of spondyloarthritis. Anti-CD74 antibody could potentially be a biomarker for the diagnosis of spondyloarthritis, but many open questions remain.

Introduction

Spondyloarthritis, which was divided into axial spondyloarthritis (axe-SpA) and peripheral spondyloarthritis, is a group of chronic inflammatory diseases characterized by inflammation and chronic back pain, including ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axe-SpA), psoriatic arthritis (PsA), reactive arthritis, inflammatory bowel disease related arthritis, enthesitis-related juvenile idiopathic arthritis and undifferentiated arthritis [1]. The prevalence of spondyloarthritis is estimated at 0.45% to 1.9% [2]. The classification and diagnosis of spondyloarthritis depend mainly on the imaging of the sacroiliac joint or the presence of human leukocyte antigen-B27 (HLA-B27) [3]. Magnetic resonance imaging (MRI) could detect inflammatory changes of the sacroiliac joint in early stage and realize the early identification of spondyloarthritis patients [4], but there was still a delay of 5 to 10 years between the onset and diagnosis of spondyloarthritis [5]. HLA-B27 has good sensitivity and specificity, but its positive rate in healthy individuals is up to 10% [6]. Autoantibodies are one of the most common biomarkers for the diagnosis in autoimmune diseases. In some occasion, autoantibodies may be detected in serum years before the abnormal autoantigens and imaging, with good sensitivity [7]. Recent studies have shown that early diagnosis could lead to better outcomes, so there is an unmet need for biomarkers that could potentially identify spondyloarthritis patients and serve as reliable tools for differential diagnosis.

Cluster of Differentiation 74 (CD74), also known as human leukocyte antigen class II gamma chain or invariant chain, plays a role in the assembly and transport of human histocompatibility leukocyte antigen class II molecules and could prevent premature binding of peptides to newly assembled Class II HLA molecules [8]. CD74 participates in antigen presentation and is expressed on several immune cells, such as B cells, dendritic cells and macrophages [9], all of which are pivotal in pathogenesis of inflammation. Besides, CD74 is known to be the high affinity receptor for macrophage migration inhibitory factor (MIF) [10]. Binding of CD74 to MIF may lead to the activation of nuclear factor κB (NF-κB), which is critical in the production of proinflammatory cytokines [10], [11], [12]. The extracellular portion of CD74 includes thyroglobulin type-1 and class II-associated invariant chain peptide (CLIP) domains. The binding of CLIP antibody to CD74 could lead to cell activation and production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) [11]. Recent studies have shown that CD74 might play a role in a variety of inflammatory or autoimmune diseases, including atherosclerosis, lupus, and diabetes [9]. In terms of spondyloarthritis, MIF is elevated in the serum of patients and is associated with spinal progression of AS [13]. In 2013, Baerlecken et al. provided first evidence that anti-CD74 antibody may be a biomarker in spondyloarthritis diagnosis [14]. These studies preliminarily demonstrated that anti-CD74 antibody might play an important role in the pathogenesis and diagnosis of spondyloarthritis [14], [15], [16]. Nevertheless, the results of the studies on anti-CD74 antibodies in spondyloarthritis were inconsistent [14, 17]. Therefore, we conducted this meta-analysis to evaluate the levels of anti-CD74 IgG and IgA antibodies in spondyloarthritis patients compared with health controls, and the diagnostic value of anti-CD74 IgG and IgA antibodies in patients with spondyloarthritis.

Section snippets

Materials and methods

The present systematic review and meta-analysis was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [18] and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) [19] guidelines.

Search results and characteristics of studies

A total of 55 article were identified in PubMed (17), Web of Science (27) and Medline (11) (Fig. 1). After removing the duplicates, we reviewed the titles and abstracts of 34 articles and only read the full text of 12 articles. Finally, nine studies were included for analysis [7,14–17,21–24]. The main characteristics of the included studies were shown in Table 1. Among which, six studies [7,14,16,17,22,24] compared the anti-CD74 IgG levels between spondyloarthritis patients and health controls,

Discussion

The present study systematically reviewed the role of anti-CD74 antibody in spondyloarthritis. We found that anti-CD74 IgG and IgA antibodies were significantly increased in the serum of spondyloarthritis patients compared with health controls. The results also indicated that anti-CD74 IgG and IgA antibodies had moderate sensitivity and high specificity in the diagnosis of spondyloarthritis. All these suggested that anti-CD74 IgG and IgA antibodies could potentially be used as biomarkers for

Conclusions

Our study indicated that anti-CD74 IgG and IgA antibodies were significantly increased in spondyloarthritis patients, and had high diagnostic specificity of spondyloarthritis. Anti-CD74 antibody could potentially be a biomarker for the diagnosis of spondyloarthritis, but many open questions remain.

Declarations of Competing Interest

All authors declare they have no conflicts of interest.

Acknowledgments

We really appreciate the efforts of all the researchers whose articles were included in this study.

Funding

The study was sponsored by the National Natural Science Foundation of China (81773514 and 82073655).

Patient consent

Not required.

Ethics approval

Not required.

References (26)

  • J. Neefjes et al.

    Towards a systems understanding of MHC class I and MHC class II antigen presentation

    Nat Rev Immunol

    (2011)
  • F. Borghese et al.

    CD74: an emerging opportunity as a therapeutic target in cancer and autoimmune disease

    Expert Opin Ther Targets

    (2011)
  • L. Leng et al.

    MIF signal transduction initiated by binding to CD74

    J Exp Med

    (2003)
  • Cited by (0)

    1

    Shanshan Xu and Xiaoyi Zhang contributed equally to this work and should be considered co-first author.

    View full text