MAGE-B2 Autoantibody: A New Biomarker for Pediatric Systemic Lupus Erythematosus

Abstract

Objective-Melanoma-associated antigen gene B2 (MAGE-B2) encodes an embryonic antigen normally silenced after birth except in testis and placenta. We identified the MAGE-B2 gene and autoantibodies in pediatric patients with systemic lupus erythematosus (SLE) glomerulonephritis. Our purpose herein was to determine the prevalence of MAGE-B2 autoantibodies in association with active SLE, as well as to infer a pathogenetic role of MAGE-B2 protein through its distribution in cells and tissues.Methods-A cross-sectional study analyzed the frequency of MAGE-B2 autoantibodies in 40 pediatric SLE patients, 23 adult controls, and 16 pediatric juvenile rheumatoid arthritis (JRA) patients using Western blots containing recombinant MAGE-B2. SLE disease activity index 2000 (SLEDAI-2K) and British Isles Lupus Assessment Group (BILAG) index measured SLE disease activity. Tissue distribution of MAGE-B2 protein was also assessed by immunohistochemistry, immunofluorescence, and Western blots.Results-Seventeen (43%) of 40 pediatric SLE patients had MAGE-B2 autoantibodies as compared to 0 of 16 JRA patients and 2 of 23 adult controls. SLE disease activity was significantly higher in MAGE-B2 autoantibody-positive vs. autoantibody-negative patients (SLEDAI-2K: mean 10.9 vs. 5.2, p=0.013; BILAG: mean 15.3 vs. 6.3, p=0.023). Active nephritis was more prevalent (60% vs. 24%) in MAGE-B2 autoantibody-positive SLE patients. MAGE-B2 protein was visualized in SLE kidney proximal convoluted tubules and in tumor epithelial cells, but not in lymphoblastoid cells. Conclusion-MAGE-B2 autoantibody appears to be a clinically relevant biomarker for pediatric SLE disease activity and nephritis.

Biomarkers for Lupus Nephritis: A Critical Appraisal

“…Literature search reveals quite a number of cross-sectional studies on the relationship between novel biomarkers and activity of lupus nephritis [ 13 , 63 – 69 , 73 – 78 ]. These are summarized in Table 1 (serum biomarkers) and Table 2 (urine biomarkers).…”

Laboratory medicine in pediatric lupus

“…Another recently described autoantibody with possible clinical relevance in pediatric lupus is directed against the melanomaassociated antigen gene (MAGE)-B2. Seventeen of forty pediatric lupus patients had autoantibodies to MAGE-B2 as compared to only two of twenty-three adult controls [19]. Disease activity and active nephritis were higher in MAGE-B2-positive versus MAGE-B2-negative patients [19].…”

Role(s) of G3BPs in Human Pathogenesis

“…Several proteins and miRs regulate G3BP1 at the post-transcriptional level. Many of these proteins interact with 5'-untranslated region (5'-UTR) (Hoftman et al, 2008;Lee et al, 2020;Somasekharan et al, 2015) of G3BP1, than with 3'-untranslated region (3'-UTR) (Deng et al, 2015;Liu et al, 2021;Lv et al, 2017). In contrast, many miRs have been identified to bind the 3'-UTR of G3BP1 and subsequently downregulate its expression.…”

“…Thus, YB-1 regulates G3BP1 availability for SG assembly (Zhang et al, 2019a) and there is a strong association between YB-1 and G3BP1 expression in human sarcomas (Somasekharan et al, 2015). Lee and colleagues showed that Melanoma-associated antigen gene B2 (MAGE-B2), which is normally found in testicular tissue but is abnormally expressed in tumors (Hoftman et al, 2008), can interact with the 5′-UTR of G3BP1. This interaction results in increased translation of G3BP1 (Lee et al, 2020).…”