Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps

Publication date: March 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 3
Author(s): Jia Song, Hai Wang, Ya-Na Zhang, Ping-Ping Cao, Bo Liao, Zhe-Zheng Wang, Li-Li Shi, Yin Yao, Guan-Ting Zhai, Zhi-Chao Wang, Li-Meng Liu, Ming Zeng, Xiang Lu, Heng Wang, Xiang-Ping Yang, Di Yu, Claus Bachert, Zheng Liu
BackgroundThe contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear.ObjectiveWe sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP.MethodsWe graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cμ and Iε-Cγ circle transcripts was detected by using seminested PCR.ResultsIncreased formation of eLTs with germinal center–like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cμ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps.ConclusioneLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP.



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