Rheumatology International

, Volume 38, Issue 5, pp 831–836 | Cite as

CXCL13 levels in serum but not in saliva are elevated in Asian Indian patients with primary Sjögren’s syndrome

  • Santosh Kumar Mandal
  • Pulukool Sandhya
  • Jayakanthan Kabeerdoss
  • Janardana Ramya
  • Gowri Mahasampath
  • Debashish Danda


Human and animal model studies suggest CXCL13 is a potential biomarker in primary Sjögren’s syndrome (pSS). CXCL13 has not been studied in Indian patients with pSS. pSS cases classified by American European Consensus Group (AECG) or American college of Rheumatology(ACR) 2012 criteria, attending rheumatology clinic between July 2014 and July 2015 were included. Hospital staff and healthy, non-blood related family members of patients constituted the control group. pSS cases underwent clinical evaluation, laboratory investigations, ESSDAI and ESSPRI scoring. Unstimulated saliva was collected by the spitting method. Salivary and serum CXCL13 were quantified by indirect ELISA. CXCL13 positivity was determined using Receiver Operator Characteristic (ROC) curve. STATA13.1 (StataCorpLP,Texas,USA) software was used for statistical analysis. In this study, 45 pSS cases and 42 healthy controls were recruited. In pSS, median levels of serum CXCL13, but not salivary CXCL13 was significantly higher as compared to the corresponding levels in healthy controls (p < 0.001). Using cutoff of 43.03 pg/ml obtained by ROC, serum CXCL13 positivity was seen in 31/43(72.1%) cases and 10/34 (29.4%) controls, respectively. Serum CXCL13 levels among pSS patients on treatment, treatment naïve patients and healthy controls were statistically different. Serum CXCL13 positivity was associated with oral symptoms (p = 0.02), ocular signs (p = 0.03) and hyperglobulinemia (p = 0.01). There was no association of salivary CXCL13 level with any of the clinical variables. While serum CXCL13 was elevated in pSS, salivary CXCL13 was not. In conclusion, serum CXCL13 positivity was found to be associated with oral symptoms, ocular signs and hyperglobulinemia in pSS.


Saliva Serum CXCL13 Sjogren’s syndrome India 



We acknowledge the funding received from Christian Medical College (CMC) fluid research grant for the study.

Compliance with ethical standards

Conflict of interest

The authors report that they have no conflicts of interests.

Ethical approval

This study was approved by the Institutional review board (IRB) & Ethics committee and was conducted in accordance with the Helsinki declaration of 1975, as revised in 2008.

Informed consent

Informed consent has been obtained from all participants.


  1. 1.
    Gabriel SE, Michaud K (2009) Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res Ther 11:229. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Vitali C, Bombardieri S, Jonsson R et al (2002) Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61:554–558. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Shiboski SC, Shiboski CH, Criswell LA et al (2012) American College of Rheumatology classification criteria for Sjögren’s syndrome: a data-driven, expert consensus approach in the Sjögren’s International Collaborative Clinical Alliance cohort. Arthritis Care Res 64:475–487CrossRefGoogle Scholar
  4. 4.
    Christodoulou MI, Kapsogeorgou EK, Moutsopoulos HM (2010) Characteristics of the minor salivary gland infiltrates in Sjögren’s syndrome. J Autoimmun 34:400–407. CrossRefPubMedGoogle Scholar
  5. 5.
    Xanthou G, Polihronis M, Tzioufas AG, et al (2001) “Lymphoid” chemokine messenger RNA expression by epithelial cells in the chronic inflammatory lesion of the salivary glands of Sjögren’s syndrome patients: possible participation in lymphoid structure formation. Arthritis Rheum 44:408–418.<408::AID-ANR60>3.0.CO;2-0CrossRefPubMedGoogle Scholar
  6. 6.
    Barone F, Bombardieri M, Manzo A et al (2005) Association of CXCL13 and CCL21 expression with the progressive organization of lymphoid-like structures in Sjögren’s syndrome. Arthritis Rheum 52:1773–1784. CrossRefPubMedGoogle Scholar
  7. 7.
    Ansel KM, Ngo VN, Hyman PL et al (2000) A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 406:309–314. CrossRefPubMedGoogle Scholar
  8. 8.
    Luther SA, Lopez T, Bai W et al (2000) BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis. Immunity 12:471–481CrossRefPubMedGoogle Scholar
  9. 9.
    Amft N, Curnow SJ, Scheel-Toellner D et al (2001) Ectopic expression of the B cell-attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in Sjögren’s syndrome. Arthritis Rheum 44:2633–2641CrossRefPubMedGoogle Scholar
  10. 10.
    Hjelmervik TOR, Petersen K, Jonassen I et al (2005) Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren’s syndrome patients from healthy control subjects. Arthritis Rheum 52:1534–1544. CrossRefPubMedGoogle Scholar
  11. 11.
    Salomonsson S, Jonsson MV, Skarstein K et al (2003) Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjögren’s syndrome. Arthritis Rheum 48:3187–3201. CrossRefPubMedGoogle Scholar
  12. 12.
    Salomonsson S, Larsson P, Tengnér P et al (2002) Expression of the B cell-attracting chemokine CXCL13 in the target organ and autoantibody production in ectopic lymphoid tissue in the chronic inflammatory disease Sjögren’s syndrome. Scand J Immunol 55:336–342CrossRefPubMedGoogle Scholar
  13. 13.
    Kramer JM, Klimatcheva E, Rothstein TL (2013) CXCL13 is elevated in Sjögren’s syndrome in mice and humans and is implicated in disease pathogenesis. J Leukoc Biol 94:1079–1089. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Seror R, Gottenberg JE, Devauchelle-Pensec V et al (2013) European league against rheumatism Sjögren’s syndrome disease activity index and European League Against Rheumatism Sjögren’s syndrome patient-reported index: a complete picture of primary Sjögren’s syndrome patients. Arthritis Care Res 65:1358–1364. CrossRefGoogle Scholar
  15. 15.
    Chisholm DM, Mason DK (1968) Labial salivary gland biopsy in Sjögren’s disease. J Clin Pathol 21:656–660. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Jayakanthan K, Ramya J, Mandal SK et al (2016) Younger patients with primary Sjögren’s syndrome are more likely to have salivary IgG anti-muscarinic acetylcholine receptor type 3 antibodies. Clin Rheumatol 35:657–662. CrossRefPubMedGoogle Scholar
  17. 17.
    Kabeerdoss J, Sandhya P, Mandal SK et al (2016) High salivary soluble L-selectin and interleukin-7 levels in Asian Indian patients with primary Sjögren’s syndrome. Clin Rheumatol 35:3063–3067. CrossRefPubMedGoogle Scholar
  18. 18.
    Shiboski CH, Shiboski SC, Seror R et al (2016) 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren’s syndrome A consensus and data-driven methodology involving three international patient cohorts. Ann Rheum. (Dis annrheumdis–2016–210571)Google Scholar
  19. 19.
    Nocturne G, Seror R, Fogel O et al (2015) CXCL13 and CCL11 serum levels and lymphoma and disease activity in primary Sjögren’s syndrome. Arthritis Rheumatol Hoboken NJ 67:3226–3233. CrossRefGoogle Scholar
  20. 20.
    Jin L, Yu D, Li X et al (2014) CD4 + CXCR5+ follicular helper T cells in salivary gland promote B cells maturation in patients with primary Sjogren’s syndrome. Int J Clin Exp Pathol 7:1988–1996PubMedPubMedCentralGoogle Scholar
  21. 21.
    García-Carrasco M, Mendoza-Pinto C, Jiménez-Hernández C et al (2012) Serologic features of primary Sjögren’s syndrome: clinical and prognostic correlation. Int J Clin Rheumatol 7:651–659. CrossRefGoogle Scholar
  22. 22.
    Nishikawa A, Suzuki K, Kassai Y et al (2016) Identification of definitive serum biomarkers associated with disease activity in primary Sjögren’s syndrome. Arthritis Res Ther 18:106. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Lee K-E, Kang J-H, Yim Y-R et al (2017) Predictive significance of CCL21 and CXCL13 levels in the minor salivary glands of patients with Sjögren’s syndrome. Clin Exp Rheumatol 35(2):234–240PubMedGoogle Scholar
  24. 24.
    Hernández-Molina G, Michel-Peregrina M, Hernández-Ramírez DF et al (2011) Chemokine saliva levels in patients with primary Sjögren’s syndrome, associated Sjögren’s syndrome, pre-clinical Sjögren’s syndrome and systemic autoimmune diseases. Rheumatol Oxf Engl 50:1288–1292. CrossRefGoogle Scholar
  25. 25.
    Delaleu N, Mydel P, Kwee I et al (2015) High fidelity between saliva proteomics and the biologic state of salivary glands defines biomarker signatures for primary Sjögren’s syndrome. Arthritis Rheumatol 67:1084–1095. CrossRefPubMedGoogle Scholar
  26. 26.
    Henson BS, Wong DT (2010) Collection, storage, and processing of saliva samples for downstream molecular applications. In: Oral Biology. Humana Press, Totowa, pp 21–30CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Clinical Immunology and RheumatologyChristian Medical CollegeVelloreIndia
  2. 2.Department of RheumatologyRabindranath Tagore international institute of cardiac sciencesKolkataIndia
  3. 3.St. Stephens Hospital, Tis HazariNew DelhiIndia
  4. 4.St. John’s Medical CollegeBengaluruIndia
  5. 5.Department of BiostatisticsChristian Medical CollegeVelloreIndia

Personalised recommendations