RNA-sequencing study of peripheral blood mononuclear cells in sporadic Ménière's disease patients: possible contribution of immunologic dysfunction to the development of this disorder

Abstract

To date, the pathogenesis of Ménière's disease (MD) remains unclear. This study aims to investigate the possible relationship between potential immune system-related genes and sporadic MD. The whole RNA-sequencing (RNA-seq) technology was used to analyse the transcriptome of peripheral blood mononuclear cells of three MD patients and three control individuals. Of 366 differentially expressed genes (DEGs), 154 genes were up-regulated and 212 genes were down-regulated (|log fold change| > 1 and P < 0·05). Gene ontology (GO) enrichment analysis illustrated that immune relevant factors played a key role in the pathogenesis of MD. Of 366 DEGs, we focused upon analysing the possible immune-related genes, among which the significantly up-regulated genes [glutathione S-transferase mu 1 (GSTM1), transmembrane protein 176 (TMEM176)B, TMEM176A] and down-regulated genes [solute carrier family 4 member (SLC4A)10 and SLC4A1] especially drew our attention. The mRNA expression levels of GSTM1, TMEM176B, TMEM176A, SLC4A1 and SLC4A10 were analysed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The serum concentration of GSTM1, TMEM176B and SLC4A10 proteins were measured by enzyme-linked immunosorbent assay (ELISA). Considering the results of qRT-PCR and ELISA, it was noteworthy that GSTM1 exhibited the highest fold change between two groups, which was consistent with the deep sequencing results by RNA-seq. In conclusion, our study first offers a new perspective in MD development on the basis of RNA expression patterns, suggesting that immune factors might be involved in the MD pathogenesis. Remarkably, GSTM1 might be a possible candidate gene for the diagnostic biomarker of MD and provides the basis for further biological and functional investigations.

Rare Variants of Putative Candidate Genes Associated With Sporadic Meniere's Disease in East Asian Population

“…Recent studies have found that basal levels of proinflammatory cytokines were increased in some patients with MD (55,56). Gene expression study using mRNA also demonstrated that immune-related genes such as GSTM1, TMEM176A, and TMEM176B were highly expressed in MD patients compared to normal controls (57). Through our study, the PTPN22 may be of particular interest to support the immuneassociated process in MD.…”

Can Hashimoto's thyroiditis cause vertigo? [Czy choroba Hashimoto może być przyczyną zawrotów głowy?]

“…The risk of Meniere's disease is greater in patients with a history of head trauma, including fractures of the skull base, labyrinthitis, or syphilis. Autoimmune disorders, including HT, remain a potential mechanism for some cases of Meniere's disease [45][46][47][48][49]. Tamura (1964) was the first to find the correlation between Meniere's disease and autoimmune diseases [10] and assumed that in patients with Meniere's disease, hypothyroidism could be involved in the increase in the fluid pressure in the inner ear and, consequently, the development of endolymphatic hydrops.…”

“…Their REVIEW studies confirmed statistically higher serum levels of anti-TPO and anti-TG antibodies in patients with Meniere 's disease compared to groups of patients with vestibular disorders other than endolymphatic hydrops. Anti-TPO and anti-TG antibodies could reach the structures of the inner ear through the blood vessels, and due to the reaction with the cells of the endolymphatic sac they could increase endolymphatic pressure in the inner ear [45][46][47][48][49]. However, the precise mechanisms of this process have not been confirmed yet and are still hypothetical.…”

“…Ryzyko wystąpienia choroby Meniere'a jest większe wśród chorych, którzy w przeszłości doznali urazów głowy, w tym złamania podstawy czaszki, zapalenia błędnika, a także po przechorowaniu kiły. Pewną rolę w jej występowaniu przypisuje się schorzeniem z autoagresji, o podłożu autoimmunologicznym, w tym między innymi chorobie Hashimoto [45][46][47][48][49].…”

“…Związek ten, choć jak dotąd niepotwierdzony, sugerują autorzy, którzy w swoich badaniach wykryli statystycznie wyższe miano przeciwciał anty-TPO i anty-TG w surowicy krwi chorych na chorobę Meniere'a w korelacji do grupy chorych z zaburzeniami równowagi na innym tle niż wodniak endolimfatyczny. Zdaniem badaczy przeciwciała anty-TPO i anty-TG drogą naczyń krwionośnych mogą wnikać w struktury ucha wewnętrznego i na skutek reakcji z komórkami woreczka endolimfatycznego generować wzrost ciśnienia śródchłonki w jego wnętrzu [45][46][47][48][49]. Dotychczas dokładne mechanizmy tego procesu nie zostały jednak udowodnione i wciąż są tylko hipotezą.…”