Anti-CD74 antibodies in spondyloarthritis: A systematic review and meta-analysis
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)
- et al.
Spondyloarthritis
Lancet
(2011) - et al.
Autoantibodies in Spondyloarthritis, Focusing on Anti-CD74 Antibodies
Front Immunol
(2019) - et al.
Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival
Blood
(2006) - et al.
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement
Int J Surg
(2010) - et al.
Summary receiver operating characteristic curve analysis techniques in the evaluation of diagnostic tests
Ann Thorac Surg
(2005) - et al.
One year in review 2017: spondyloarthritis
Clin Exp Rheumatol
(2018) - et al.
Prevalence of spondyloarthritis and its subtypes in southern Sweden
Ann Rheum Dis
(2011) - et al.
The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection
Ann Rheum Dis
(2009) - et al.
Does the site of magnetic resonance imaging abnormalities match the site of recent-onset inflammatory back pain? The DESIR cohort
Ann Rheum Dis
(2013) - et al.
The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria?
Arthritis Rheum
(2005)
Towards a systems understanding of MHC class I and MHC class II antigen presentation
Nat Rev Immunol
CD74: an emerging opportunity as a therapeutic target in cancer and autoimmune disease
Expert Opin Ther Targets
MIF signal transduction initiated by binding to CD74
J Exp Med
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Shanshan Xu and Xiaoyi Zhang contributed equally to this work and should be considered co-first author.