Short communicationComparison of the chemokine profiles in the bronchoalveolar lavage fluid between IgG4-related respiratory disease and sarcoidosis: CC-chemokine ligand 1 might be involved in the pathogenesis of sarcoidosis
Introduction
Immunoglobulin G4-related disease (IgG4-RD) is a chronic fibrotic inflammatory disease that presents with multi-organ involvement characterized by the infiltration of IgG4-positive plasma cells and elevated serum levels of IgG4 [1]. On the other hand, sarcoidosis is a systemic disease of unknown cause that is characterized by granulomas in various organs and which involves the lungs and lymphatic system, such as the hilar lymph nodes [2], [3]. Both of the diseases develop through lymphatic routes of the lungs, and bilateral hilar lymphadenopathy (BHL) is frequently observed on chest computed tomography (CT). Thus, the images of IgG4-RD often mimic findings of sarcoidosis on chest CT [4], [5]. However, the clinical conditions of the two diseases are completely different. While T-helper (Th)1 immune responses are predominant in the organs affected by sarcoidosis [2], [3], the autoimmunity of IgG4-RD is attributed to the activation of the Th2 immune response and the Th2-cell responses at the affected sites [1]. We previously reported that the cytokine profiles in the bronchoalveolar lavage fluid (BALF) of IgG4-related respiratory disease (IgG4-RRD) with BHL on chest CT more closely resembled the Th2 response in patients with eosinophilia than it did in patients with sarcoidosis [5].
In a study investigating the chemokine ligands and chemokine receptors in patients with IgG4-related sclerosing cholangitis/pancreatitis, Zen et al. reported that CC-chemokine ligand (CCL)1-CC-chemokine receptor (CCR)8 interaction may play a critical role in recruiting inflammatory cells, particularly Th2 lymphocytes and regulatory T cells (Tregs) [6]. However, few reports have explored the chemokine responses in IgG4-RRD and sarcoidosis. The present study investigated the chemokines in the BALF of patients with the two diseases and analysed the differences in the chemokine profiles of patients with the two diseases in an attempt to shed light on the pathogeneses with regard to the cytokines [5].
Section snippets
Material and methods
The Ethics Committee of Shinshu University School of Medicine approved this study (Approval Number: 3458). We re-evaluated the same 44 untreated patients (IgG4-RRD, n = 11; sarcoidosis, n = 33) who visited our hospital (Shinshu University Hospital) from September 2007 to March 2014 [5]. Written informed consent was obtained from all patients. Eleven consecutive patients with IgG4-RRD showed BHL and bronchial wall thickening on chest CT and underwent a transbronchial lung biopsy and bronchial
Results
The 11 patients with IgG4-RRD (male, n = 9; female, n = 2; median age, 62 years [range: 50–78]) had a higher percentage of male patients (p < 0.01) and were older (p < 0.05) in comparison to the 33 patients with sarcoidosis (male, n = 9; female, n = 24; median age, 53 years [range: 21–77]). No significant differences in the number of smokers or smoking status were noted.
General blood tests were performed in 11 patients with IgG4-RRD and 31 patients with sarcoidosis. The serum IgG (IgG4-RRD,
Discussion
Few reports have described the cytokine and chemokine profiles in the BALF of patients with IgG4-RRD. To our knowledge, this is the first report showing that the CCL26 values in the BALF of IgG4-RRD patients were significantly higher than those in sarcoidosis patients. The CCL26 chemokine was reported to be highly expressed by bronchial epithelial cells on treatment with IL-13 in Th2-dominant eosinophilic asthma [8]. We previously reported that the eosinophil fractions and the IL-13 values in
Conclusions
The CCL1 values in the BALF of sarcoidosis patients were significantly higher than those in IgG4-RRD patients. CCL1 might reflect disease activity and may be involved in the pathogenesis of sarcoidosis in a manner that is more closely related to Th1 than to Th2.
Funding information
This study was supported by the Research Program of Intractable Disease, the Ministry of Health, Labor, and Welfare of Japan (No. H29-Nanchi-Ippan-058), and the Japan Society for the Promotion of Science (No. 15K09169).
Conflict of interest
The authors have no conflict of interest to declare.
Acknowledgement
We thank Dr. Shigeyuki Kawa, Professor at Matsumoto Dental University, Department of Internal Medicine, for expert advice and management of some of the IgG4-RD patients. We thank Hitomi Imamura for skilled technical assistance with the chemokine ligands measurements and Dr. Yunden Droma for help in manuscript preparation.
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The utility of serum C-C chemokine ligand 1 in sarcoidosis: A comparison to IgG4-related disease
2020, CytokineCitation Excerpt :Although sarcoidosis and IgG4-RD often have similar imaging features, the pathology of IgG4-RD is attributed to the activation of Th2 immune response at the affected sites [5]. We previously reported the cytokine and chemokine profiles of bronchoalveolar lavage (BAL) fluid (BALF) in patients with sarcoidosis and IgG4-RD, and we demonstrated that the lung lesion of IgG4-RD was more characteristic of the Th2 response than that of sarcoidosis [7,8]. C-C chemokine ligand (CCL) 1 belongs to the C-C chemokine family.
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