Bidirectional Transport of IgE by CD23 in the Inner Ear of Patients with Meniere’s Disease

Abstract

Meniere’s disease (MD) is a disorder of the inner ear characterized by episodes of spontaneous vertigo, fluctuating hearing loss, and tinnitus. Recent studies have demonstrated that IgE may play a role in the pathogenesis of MD. Patients with MD (n = 103), acoustic neuroma (n = 5), and healthy subjects (n = 72) were recruited into the study. Serum from the participants was analyzed for IgE and type 2–related cytokines. IgE and CD23 expression levels in vestibular end organs of patients, C57BL/6 mice, or mouse HEI-OC1 cells were analyzed. Finally, the role of CD23 in IgE transcytosis was assessed using HEI-OC1 cells. Serum IgE was elevated in patients with MD and positively correlated with clinical symptoms. IL-4, IL-5, IL-10, IL-13, and CD23 levels were increased in patients with MD compared with the control group. In the transcytosis assay, mouse IgE was found to be bidirectionally transported across the HEI-OC1 cell monolayer. Additionally, CD23 downregulation using a small interfering RNA approach significantly reduced the efficiency of IgE transcytosis, suggesting that IgE is transported by CD23. Furthermore, exposure to IL-4 increased CD23 expression and enhanced IgE transcytosis in the HEI-OC1 cells and primary vestibular end organs. Our study indicated that IgE may play a role in the pathophysiology of MD. In addition, CD23-mediated IgE transcytosis in the hair cells may play a critical role in initiating inflammation in the inner ear. Thus, reducing the level of IgE may be a potentially effective approach for MD treatment.

Single cell profiling reveals a reduction of CD56dim NK-cells and other immune cells in patients with Meniere disease and high levels of cytokines

“…They also reported 27.2% MD patients with high basal levels of IgE when compared to controls. However, no signi cant differences were found regarding sex, age, and other clinical features, when comparing MD patients with high levels of IgE to patients with low levels of IgE, in line with our ndings (22). Further corroborating our results, they also found increased levels of IL-4 in patients with high levels of IgE, but no differences in IL-10 between the two groups (22).…”

“…However, no signi cant differences were found regarding sex, age, and other clinical features, when comparing MD patients with high levels of IgE to patients with low levels of IgE, in line with our ndings (22). Further corroborating our results, they also found increased levels of IL-4 in patients with high levels of IgE, but no differences in IL-10 between the two groups (22). Moreover, it has been described that increased levels of IgE could be a predictor of MD transformation in patients with acute low-tone sensorineural hearing loss (19).…”

“…A recent study described increased levels of IgE, IL-4, IL-5, IL-10, and IL-13 in serum samples from 103 MD patients (22). They also reported 27.2% MD patients with high basal levels of IgE when compared to controls.…”

“…On the other hand, there are several reports of an over-expression of cytokines and IgE in MD patients (6,(18)(19)(20)(21)(22). Ma et al observed that high levels of IgE could be used as a predictor of acute low-tone SNHL recurrence and MD transformation, since patients with acute low-tone SNHL developed MD during follow-up (19).…”

“…A study using endolymphatic sac luminal uid (ELF) and serum from MD patients and acoustic neuroma patients found signi cant differences in the expression of IL-6 and TNFα in ELF, but no differences were found in the serum (47). Moreover, increased levels of IL-4 and IL-10 have been found in the serum of MD patients when compared to controls (22,45). In this study, we did not identify any differences in cytokine expression between MD patients and controls.…”