Olfactory Dysfunction in IgG4-Related Disease.

IgG4-related disease is a newly recognized systemic disease, and its elucidation is progressing. However, little is known about its sinonasal manifestations. The aim of this study was to assess the olfaction of patients with IgG4-related disease. Twenty-five patients with IgG4-related disease underwent T&T olfactometry to measure olfactory function. We analyzed the clinical features, including serum IgG4 and IgE levels, involved organs, and sinonasal computed tomography scores to explore the etiology of olfactory dysfunction. Thirteen patients with IgG4-related disease were found to have moderate to severe olfactory dysfunction (52%). There were no differences in the clinical features between the olfactory dysfunction group and the normal group. In 7 patients, the inferior turbinate was biopsied to study the correlation between olfaction score and the number of IgG4-positive cells, but no such correlation was found. Six hyposmia patients recovered to a normal state. Five patients recovered after corticosteroid treatment and 1 recovered spontaneously. We found that the prevalence of olfactory dysfunction was high in patients with IgG4-related disease and that it could be reversed. Olfactory dysfunction appears to be a novel important manifestation of IgG4-related disease.

Effects of Corticosteroid Treatment on Olfactory Dysfunction in LATY136F Knock-In Mice.

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition affecting multiple organs, including the pancreas, salivary glands, lungs, kidneys, skin, and lymph nodes. Clinically, it is characterized by elevated serum IgG and IgG4 levels and tissue infiltration by IgG4-positive plasma cells, lymphocytes, fibrosis, and phlebitis obliterans. IgG4-RD is linked to increased Th2-dominant cytokines, contributing to eosinophilia, elevated serum IgG4, and fibrosis. A notable feature is its good response to corticosteroid therapy. To investigate the effects of corticosteroid treatment on olfactory dysfunction in LATY136F knock-in mice, which exhibited increased production of Th2-type IgG1 (the murine homolog of human IgG4) and developed multiorgan tissue lesions similar to those observed in IgG4-RD patients. METHODS: LATY136F knock-in mice (n=24) were divided into groups that received prednisolone or saline at different ages. Olfactory function was assessed using a behavioral test with cycloheximide. Histological and immunohistochemical analyses were performed to evaluate the olfactory epithelium thickness as well as the presence of mature and immature olfactory neurons. RESULTS: Corticosteroid-treated mice exhibited significantly improved olfactory function compared to the controls. Histological analysis revealed a significant increase in olfactory epithelium thickness and mature (olfactory marker protein-positive) and immature (growth-associated protein 43-positive) olfactory neurons in the treated groups compared with the control group. CONCLUSION: Corticosteroid treatment effectively improved olfactory dysfunction and promoted olfactory epithelium regeneration in LATY136F knock-in mice, suggesting the potential therapeutic benefits of corticosteroid treatment for patients with IgG4-RD experiencing olfactory dysfunction. However, further research on topical nasal steroid therapy in untreated patients is warranted. The results support further investigation into topical nasal steroid therapies for treating olfactory dysfunction in untreated patients, potentially influencing clinical practice and patient management strategies for IgG4-RD globally.

Olfactory dysfunction in LATY136F knock-in mice.

OBJECTIVE: This study examined olfactory dysfunction in LATY136F knock-in mice and its pathogenic mechanism. METHODS: The olfactory function of LATY136F knock-in mice was assessed by a behavioral test using cycloheximide solution, which has been used as a mice repellant because of its peculiar smell and unpleasant taste. The tests were administered to each group of LATY136F knock-in mice and WT mice at 8, 12, 16, 20, and 24 weeks of age. After the behavioral tests to evaluate olfactory function, the mice were sacrificed for evaluations by immunohistochemistry. RESULTS: Behavioral tests to evaluate olfactory function showed that the LATY136F knock-in mice had a statistically significant level of olfactory dysfunction (P < 0.05). Histological analysis showed that the thickness of the olfactory epithelium in these mice was thinner than that in the age-matched wild type mice. There was no IgG4-RD like lesion in the olfactory epithelium of LATY136F knock-in mice. Olfactory marker protein and growth-associated protein 43 expressions in the olfactory epithelium of the LATY136F knock-in mice were markedly lesser than those in the wild type mice (P < 0.05). CONCLUSION: The present study demonstrated that olfactory disturbances occurred in LATY136F knock-in mice. Furthermore, the mechanism was suggested to be reduced regeneration of the olfactory epithelium.