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Lee, Park, Choi, Kang, Yim, Kim, Lee, Wen, Kim, Park, Lee, Yoon, and Lee: Chemokine (C-X-C Motif) Ligand 1 (CXCL1) Expression in the Minor Salivary Glands of Sjögren's Syndrome Patients
Original Article

J Rheum Dis 2016;23(5):297-303.

Published online: 31 October 2016

DOI: https://doi.org/10.4078/jrd.2016.23.5.297

Chemokine (C-X-C Motif) Ligand 1 (CXCL1) Expression in the Minor Salivary Glands of Sjögren's Syndrome Patients

Kyung-Eun Lee1, *, Dong-Jin Park1, *, Sung-Eun Choi1, Ji-Hyoun Kang1, Yi-Rang Yim1, Ji-Eun Kim1, Jeong-Won Lee1, Lihui Wen1, Tae-Jong Kim1, Yong-Wook Park1, Ji Shin Lee2, Kyung Chul Yoon3, Shin-Seok Lee1

1Division of Rheumatology, Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea

2Department of Pathology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea

3Department of Ophthalmology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea

Corresponding to: Shin-Seok Lee, Division of Rheumatology, Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, 42 Jebong-ro, Dong-gu, Gwangju 61469, Korea. E-mail: shinseok@chonnam.ac.kr

* These two authors contributed equally to this work.

Received 6 August 20167 September 2016       Accepted 21 September 2016

Copyright © 2016 The Korean College of Rheumatology

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

To evaluate the laboratory and clinical manifestations of Sjögren's syndrome (SS) association with chemokine (C-X-C motif) ligand 1 (CXCL1) expression in the ductal and acinar salivary gland epithelial cells (SGEC) of the minor salivary glands.

Methods

The sociodemographic data of 106 SS patients was obtained, and the glandular and extraglandular manifestations of the disease documented. The minor salivary glands were biopsied and the laboratory findings analyzed. European League Against Rheumatism SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) scores were obtained during biopsy. An immunohistochemical approach was used to define the expression of CXCL1 in the salivary glands.

Results

Of 106 patients, the minor salivary glands of 22 patients (20.7%) stained positively for CXCL1. Such CXCL1-positive patients exhibited higher ESSDAI scores at the time of biopsy than the CXCL1-negative patients (3.86±2.27 vs. 2.64±1.62, p=0.015). Lymphadenopathy was more frequently observed in CXCL1-positive patients, compared with CXCL1-negative patients (31.8% vs. 9.5%, p=0.014). No differences between groups were identified in terms of sociodemographic characteristics, laboratory data, or the extent of the glandular manifestation of SS.

Conclusion

The expression of CXCL1 within the ductal and acinar SGEC of SS patients is associated with lymphadenopathy and elevated clinical disease activity. CXCL1 may play an important role in the disease activity and prognosis of SS.

Keywords: Chemokines, CXCL1, Disease activity, Sjögren's syndrome

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Figure 1.
Immunohistochemistry of the expression of chemokine (C-X-C motif) ligand 1 (CXCL1) in a biopsy of the minor salivary gland of a patient with Sjögren's syndrome. Cytoplasm and membrane of acini and ductal cells from tissue sections show positive staining for CXCL1 (brown) in (A) and (B) (A, ×200; B, ×400).
jrd-23-297f1.tif
Table 1.
Comparison of the baseline sociodemographic characteristics and clinical manifestations at the time of the minor salivary gland biopsy in patients with Sjögren's syndrome
Characteristics of patient CXCL1 positive (n=22) CXCL1 negative (n=84) p-value
Age (yr) 43.64±12.75 45.87±10.95 0.458
Sicca symptom onset age (yr) 40.41±12.20 43.46±10.46 0.291
Women 22/22 (100) 81/84 (96.4) 1.000
Glandular manifestations
 Dry eye 20/22 (90.9) 82/84 (97.6) 0.190
 Dry mouth 20/22 (90.9) 81/84 (96.4) 0.276
 Schirmer's test positive rates 15/19 (78.9) 64/74 (86.5) 0.474
 BUT positive rate 20/20 (100) 75/76 (98.7) 1.000
 Salivary scan positive rates 21/21 (100) 73/79 (92.4) 0.338
 Enlargement of parotid glands 2/22 (9.1) 8/84 (9.5) 1.000
Extraglandular manifestations
 Arthralgia 18/22 (81.8) 51/84 (60.7) 0.081
 Raynaud's phenomenon 5/22 (22.7) 16/84 (19.0) 0.765
 GER 1/22 (4.5) 12/84 (14.3) 0.294
 Lymphadenopathy 7/22 (31.8) 8/84 (9.5) 0.014
 Autoimmune thyroiditis 2/22 (9.1) 8/84 (9.5) 1.000
 ILD/pulmonary fibrosis 3/22 (13.6) 3/84 (3.6) 0.102
 Renal involvement 2/22 (9.1) 3/84 (3.6) 0.276
 Psychosis 0/22 (0) 3/84 (3.6) 1.000
 Serositis 1/22 (4.5) 2/84 (2.4) 0.506
 Carpal tunnel syndrome 0/22 (0) 2/84 (2.4) 1.000
 Lymphoma 0/22 (0) 1/84 (1.2) 1.000
 Sclerodactyly 0/22 (0) 1/84 (1.2) 1.000

Unless otherwise specified, data are shown as means±standard deviations and number (%). CXCL1: chemokine (C-X-C motif) ligand 1, BUT: tear film break-up time, GER: gastroesophageal reflux, ILD: interstitial lung disease.

Table 2.
Comparison of the laboratory manifestations, focus score, and clinical index by CXCL1 level in patients with Sjögren's syndrome
Characteristics of patient CXCL1 positive (n=22) CXCL1 negative (n=84) p-value
Laboratory manifestations
 WBC (/mm3) 5,555±2,028 5,345±2,002 0.794
 Lymphocyte (/mm3) 1,600±524.5 1,771±678.7 0.335
 Hemoglobin (g/dL) 11.80±1.894 12.33±1.389 0.348
 Platelet (×103/mm3) 245.7±62.41 227.9±69.11 0.117
 C3 (mg/dL) 90.29±28.32 101.5±22.76 0.098
 C4 (mg/dL) 21.59±11.30 21.63±10.12 0.989
 CH50 (U/mL) 47.70±18.95 51.36±15.06 0.801
 Ig G (mg/dL) 2209±856.1 1980±586.7 0.295
 ESR (mm/hr) 48.91±33.58 39.62±26.35 0.272
 CRP (mg/dL) 0.534±0.866 0.357±0.611 0.776
 RF (IU/mL) 52.63±110.0 35.91±55.66 0.848
 Anti-SS-A/Ro (U/mL) 148.5±78.85 156.4±80.67 0.680
 Anti-SS-B/La (U/mL) 50.62±68.15 40.60±67.48 0.264
Focus score 1.70±0.93 1.95±0.98 0.281
ESSDAI 8.36±4.10 4.96±3.24 0.001
SSDDI 1.05±0.84 0.92±0.95 0.320

Data are shown as means±standard deviations. CXCL1: chemokine (C-X-C motif) ligand 1, WBC: white blood cell, Ig: immunoglobulin, ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, RF: rheumatoid factor, ESSDAI: EULAR Sjögren's syndrome disease activity index, SSDDI: Sjögren's syndrome disease damage index.

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