Low levels of DDB1- and CUL4-associated factor 12 (DCAF12) and heat shock protein family A member 1A (HSPA1A) in peripheral blood were detected in myasthenia gravis (MG) using reverse transcription-polymerase chain reaction (RT-PCR) and could become diagnostic biomarkers, according to a study published in BioMed Research International

As with every autoimmune disease, the immunologic cell imbalance is what drives the pathogenesis of MG. Autoantibodies and proinflammatory cytokines ultimately impair the neuromuscular junction, causing the typical motor symptoms of the disease.

Serological tests for autoantibodies are the main diagnostic approach for MG. Still, this is not a perfect method. These autoantibodies levels do not correlate with severity or treatment responsiveness; similarly, up to 10% of patients will not show serum antibodies with commercial diagnostic tests. 

“The differences in treatment response among MG patients highlight the need to identify new additional biomarkers to supplement the existing diagnostic toolkit,” the authors said. 

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The authors aimed to find differences in immune cells between patients with MG and healthy controls in this study. They downloaded the GSE85452 dataset from the gene expression omnibus database and interpreted data with the limma package to distinguish between the expressed genes of patients with MG and healthy controls.

Furthermore, the authors analyzed distinct immune cell expressions by single-sample gene set enrichment analysis. In contrast, the modules linked to the immune cell analysis were evaluated using weighted gene coexpression network analysis.

RT-PCR of mononuclear cells confirmed all of the hub genes in the peripheral blood smears of the patients with MG. Then, the authors plotted receiver operating characteristics (ROC) curves for analysis. 

CD56bright natural killer cell-associated modules were identified using weighted gene coexpression network analysis and single-sample gene set enrichment analysis. Overall, CD56bright natural killer cells were deficient in the peripheral blood of patients with MG.

Notably, RT-PCR showed that compared to healthy controls, DCAF12 and HSPA1A levels in the peripheral blood of patients with MG were significantly reduced. Regarding MG diagnosis accuracy, the ROC curve results of DCAF12 and HSPA1A messenger RNA in MG diagnosis were 0.780 and 0.830, respectively.

“CD56bright [natural killer] cell is lower in MG patients and may affect MG occurrence. DCAF12 and HSPA1A are lowly expressed in [peripheral blood mononuclear cells] of MG patients and may serve as the diagnostic biomarkers of MG,” the authors concluded. 

Reference

Nong W, Huang F, Mao F, Lao D, Gong Z, Huang W. DCAF12 and HSPA1A may serve as potential diagnostic biomarkers for myasthenia gravisBiomed Res Int. 2022;2022:8587273. doi:10.1155/2022/8587273