Elsevier

Cytokine

Volume 120, August 2019, Pages 125-129
Cytokine

Short communication
Comparison 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

https://doi.org/10.1016/j.cyto.2019.04.017Get rights and content

Highlights

  • CCL1 is usually considered as Th2-related chemokine such as asthma.

  • Higher CCL1 was seen in the BALF of sarcoidosis patients than IgG4-RRD patients.

  • The high CCL1 in BALF correlated with several cytokines of sarcoidosis patients.

Abstract

Background

We previously reported that the cytokine profiles in the bronchoalveolar lavage fluid (BALF) of IgG4-related respiratory disease (IgG4-RRD) more closely resemble the T-helper (Th) 2 response than sarcoidosis. The present study aimed to assess the chemokines in the BALF of IgG4-RRD and sarcoidosis in order to evaluate any possible associations between these chemokines and other markers.

Methods

We examined 12 chemokines using a MILLIPLEX® MAP Kit (Millipore, Darmstadt, Germany) in the same BALF samples of the same 44 patients (IgG4-RRD, n = 11; sarcoidosis, n = 33) in which we had previously evaluated the cytokines.

Results

The levels of CC-chemokine ligand (CCL)26 in the BALF of IgG4-RRD patients (median 24.5, range 3.1–401.1 pg/mL) were significantly higher than those in the BALF of sarcoidosis patients (median 3.1, range 3.1–155.6 pg/mL, p < 0.05). Interestingly, the BALF levels of CCL1 in the sarcoidosis patients (median 13.1, range 0.1–106.9 pg/mL) were significantly higher than those of the IgG4-RRD patients (median 9.8, range 0.1–14.7 pg/mL, p < 0.05). Furthermore, the CCL1 levels in the BALF were correlated with the total cell count (ρ = 0.539, p < 0.001), lymphocyte fraction (R = 0.406, P < 0.05), lymphocyte count (R = 0.686, P < 0.001), TNF-α level, (R = 0.748, P < 0.001), and IL-2 level (R = 0.757, P < 0.001) in the BALF of sarcoidosis patients.

Conclusions

CCL1 might reflect disease activity and its involvement in the pathogenesis of sarcoidosis might be more closely related to Th1 than to Th2.

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.

References (15)

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