Unveiling the clinical and proteomic spectrum of relapsing polychondritis with respiratory involvement.

BACKGROUND: Relapsing polychondritis (RP) is a rare autoimmune disease characterized by recurrent inflammation and progressive damage to cartilage. Respiratory involvement, which has a relatively high misdiagnosis rate, is the leading cause of death in RP patients, and its underlying pathogenesis remains largely unknown. METHODS: Seventy-seven RP patients with respiratory involvement were enrolled in this study. The clinical characteristics, including imaging features, bronchoscopic findings, and treatment, were systematically analyzed. Latent class analysis (LCA) was used to classify patients at first hospitalization according to their bronchoscopic findings, and the relevant clinical parameters were evaluated. A proteomic technique was applied to detect proteins in the peripheral serum of healthy controls (HCs) and 35 patients. The differentially expressed proteins between these two groups were analyzed and verified by Western blot. RESULTS: Patients with initial respiratory involvement were less likely to have ear chondritis (14.29% vs 42.86%, p = 0.005), nasal chondritis (24.48% vs 46.43%, p = 0.048), and ocular involvement (16.33% vs 39.29%, p = 0.025). Patients can be classified into three subgroups by LCA based on bronchoscopic manifestations. Patients in groups one and two are defined by cartilage damage of the central airway, with or without peripheral airway involvement, and require more non-invasive ventilation. Patients in group three are defined by cartilage damage of the entire airway, with a high frequency of ICU admission (p = 0.003), tracheostomy (p <0.001), and rescue (p = 0.001). The expression of complement- and neutrophil extracellular trap formation (NETs)-related proteins may participate in the pathogenesis of respiratory-involved RP. CONCLUSIONS: Clinical manifestations of respiratory-involved RP are nonspecific, and recognition of imaging and bronchoscopic features can facilitate the diagnosis. Patient stratification based on the patterns of airway involvement can help guide airway management strategies. Additionally, abnormalities of the complement system and NETs may play a role in its pathogenesis.