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Clinical and diagnostic significance of serum immunoglobulin A rheumatoid factor in primary Sjogren’s syndrome

Abstract

Objectives

The aim of this study was to investigate the diagnostic accuracy of rheumatoid factor (RF) isotype for the detection of primary Sjogren’s syndrome (pSS) and evaluate the clinical and serological associations of immunoglobulin (Ig) A RF in patients with pSS.

Materials and methods

RF levels were measured in 77 and 37 patients with pSS and idiopathic sicca symptoms, respectively, using ELISA and analysed with respect to clinical and laboratory disease characteristics. Receiver operating characteristic curves were used to determine and compare the diagnostic accuracy of IgA RF with other diagnostic tests.

Results

Serum levels of IgA RF were significantly higher in patients with pSS than in those with idiopathic sicca symptoms. IgA RF showed sensitivity, specificity, positive, and negative predictive values of 83.1, 78.4, 88.9, and 69.0%, respectively, for pSS diagnosis. IgA RF was associated with xerostomia, severe sialoscintigraphic grade, low unstimulated salivary flow rate (USFR), antinuclear antibody, high IgG and IgM/G RF levels, and low C3 levels in patients with pSS. IgA RF titres had positive correlations with sialoscintigraphic grade and IgG and IgG/M RF levels and had negative correlations with USFR and C3 levels.

Conclusion

Our findings confirmed the potential of IgA RF to distinguish pSS from idiopathic sicca symptoms. The presence of IgA RF in patients with pSS was associated with significantly worse exocrine function and active serologic profile. No association between IgA RF and extra-glandular manifestations was noted.

Clinical relevance

IgA RF should be the predictive and diagnostic marker in patients with pSS.

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References

  1. 1.

    Kim KS, Kim HS (2016) Successful treatment of sensorineural hearing loss in Sjogren’s syndrome with corticosteroid. Korean J Intern Med 31(3):612–615. https://doi.org/10.3904/kjim.2014.303

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Carvajal Alegria G, Guellec D, Devauchelle-Pensec V, Saraux A (2015) Is there specific neurological disorders of primary Sjogren’s syndrome? Joint Bone Spine 82(2):86–89. https://doi.org/10.1016/j.jbspin.2014.04.002

    Article  PubMed  Google Scholar 

  3. 3.

    Rischmueller M, Tieu J, Lester S (2016) Primary Sjogren’s syndrome. Best Pract Res Clin Rheumatol 30(1):189–220. https://doi.org/10.1016/j.berh.2016.04.003

    Article  PubMed  Google Scholar 

  4. 4.

    Ingegnoli F, Castelli R, Gualtierotti R (2013) Rheumatoid factors: clinical applications. Dis Markers 35(6):727–734. https://doi.org/10.1155/2013/726598

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Scott DL, Wolfe F, Huizinga TW (2010) Rheumatoid arthritis. Lancet 376(9746):1094–1108. https://doi.org/10.1016/s0140-6736(10)60826-4

    Article  PubMed  Google Scholar 

  6. 6.

    Baldini C, Pepe P, Quartuccio L, Priori R, Bartoloni E, Alunno A, Gattamelata A, Maset M, Modesti M, Tavoni A, De Vita S, Gerli R, Valesini G, Bombardieri S (2014) Primary Sjogren’s syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology (Oxford) 53(5):839–844. https://doi.org/10.1093/rheumatology/ket427

  7. 7.

    Bournia VK, Vlachoyiannopoulos PG (2012) Subgroups of Sjogren syndrome patients according to serological profiles. J Autoimmun 39(1–2):15–26. https://doi.org/10.1016/j.jaut.2012.03.001

    Article  PubMed  Google Scholar 

  8. 8.

    Lim SA, Nam S, Kwok SK, Park SH, Chung SH (2015) Serologic markers are associated with ocular staining score in primary Sjogren syndrome. Cornea 34(11):1466–1470. https://doi.org/10.1097/ico.0000000000000612

    Article  PubMed  Google Scholar 

  9. 9.

    Youinou P, Pers JO (2015) Primary Sjogren’s syndrome at a glance today. Joint Bone Spine 82(2):75–76. https://doi.org/10.1016/j.jbspin.2014.10.018

    Article  PubMed  Google Scholar 

  10. 10.

    Atkinson JC, Travis WD, Slocum L, Ebbs WL, Fox PC (1992) Serum anti-SS-B/La and IgA rheumatoid factor are markers of salivary gland disease activity in primary Sjogren’s syndrome. Arthritis Rheum 35(11):1368–1372

    Article  PubMed  Google Scholar 

  11. 11.

    Muller K, Oxholm P, Mier-Madsen M, Wiik A (1989) Circulating IgA- and IgM-rheumatoid factors in patients with primary Sjogren syndrome. Correlation to extraglandular manifestations. Scand J Rheumatol 18(1):29–31

    Article  PubMed  Google Scholar 

  12. 12.

    Peen E, Mellbye OJ, Haga HJ (2009) IgA rheumatoid factor in primary Sjogren’s syndrome. Scand J Rheumatol 38(1):46–49. https://doi.org/10.1080/03009740802366043

    Article  PubMed  Google Scholar 

  13. 13.

    Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, Rasmussen A, Scofield H, Vitali C, Bowman SJ, Mariette X (2017) 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjogren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis 76(1):9–16. https://doi.org/10.1136/annrheumdis-2016-210571

    Article  Google Scholar 

  14. 14.

    Navazesh M, Kumar SK (2008) Measuring salivary flow: challenges and opportunities. J Am Dent Assoc 139(Suppl):35s–40s

    Article  PubMed  Google Scholar 

  15. 15.

    Seror R, Bowman SJ, Brito-Zeron P, Theander E, Bootsma H, Tzioufas A, Gottenberg JE, Ramos-Casals M, Dorner T, Ravaud P, Vitali C, Mariette X, Asmussen K, Jacobsen S, Bartoloni E, Gerli R, Bijlsma JW, Kruize AA, Bombardieri S, Bookman A, Kallenberg C, Meiners P, Brun JG, Jonsson R, Caporali R, Carsons S, De Vita S, Del Papa N, Devauchelle V, Saraux A, Fauchais AL, Sibilia J, Hachulla E, Illei G, Isenberg D, Jones A, Manoussakis M, Mandl T, Jacobsson L, Demoulins F, Montecucco C, Ng WF, Nishiyama S, Omdal R, Parke A, Praprotnik S, Tomsic M, Price E, Scofield H, K LS, Smolen J, Laque RS, Steinfeld S, Sutcliffe N, Sumida T, Valesini G, Valim V, Vivino FB, Vollenweider C (2015) EULAR Sjogren’s syndrome disease activity index (ESSDAI): a user guide. RMD Open 1(1):e000022. https://doi.org/10.1136/rmdopen-2014-000022

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Vitali C, Palombi G, Baldini C, Benucci M, Bombardieri S, Covelli M, Del Papa N, De Vita S, Epis O, Franceschini F, Gerli R, Govoni M, Bongi SM, Maglione W, Migliaresi S, Montecucco C, Orefice M, Priori R, Tavoni A, Valesini G (2007) Sjogren’s syndrome disease damage index and disease activity index: scoring systems for the assessment of disease damage and disease activity in Sjogren’s syndrome, derived from an analysis of a cohort of Italian patients. Arthritis Rheum 56(7):2223–2231. https://doi.org/10.1002/art.22658

    Article  PubMed  Google Scholar 

  17. 17.

    Schall GL, Anderson LG, Wolf RO, Herdt JR, Tarpley TM Jr, Cummings NA, Zeiger LS, Talal N (1971) Xerostomia in Sjogren’s syndrome. Evaluation by sequential salivary scintigraphy. JAMA 216(13):2109–2116

    Article  PubMed  Google Scholar 

  18. 18.

    Dorner T, Egerer K, Feist E, Burmester GR (2004) Rheumatoid factor revisited. Curr Opin Rheumatol 16(3):246–253

    Article  PubMed  Google Scholar 

  19. 19.

    ter Borg EJ, Risselada AP, Kelder JC (2011) Relation of systemic autoantibodies to the number of extraglandular manifestations in primary Sjogren’s syndrome: a retrospective analysis of 65 patients in the Netherlands. Semin Arthritis Rheum 40(6):547–551. https://doi.org/10.1016/j.semarthrit.2010.07.006

    Article  PubMed  Google Scholar 

  20. 20.

    Ramos-Casals M, Solans R, Rosas J, Camps MT, Gil A, Del Pino-Montes J, Calvo-Alen J, Jimenez-Alonso J, Mico ML, Beltran J, Belenguer R, Pallares L (2008) Primary Sjogren syndrome in Spain: clinical and immunologic expression in 1010 patients. Medicine 87(4):210–219. https://doi.org/10.1097/MD.0b013e318181e6af

    Article  Google Scholar 

  21. 21.

    Fauchais AL, Martel C, Gondran G, Lambert M, Launay D, Jauberteau MO, Hachulla E, Vidal E, Hatron PY (2010) Immunological profile in primary Sjogren syndrome: clinical significance, prognosis and long-term evolution to other auto-immune disease. Autoimmun Rev 9(9):595–599. https://doi.org/10.1016/j.autrev.2010.05.004

    Article  Google Scholar 

  22. 22.

    Martel C, Gondran G, Launay D, Lalloue F, Palat S, Lambert M, Ly K, Loustaud-Ratti V, Bezanahary H, Hachulla E, Jauberteau MO, Vidal E, Hatron PY, Fauchais AL (2011) Active immunological profile is associated with systemic Sjogren’s syndrome. J Clin Immunol 31(5):840–847. https://doi.org/10.1007/s10875-011-9553-3

    Article  PubMed  Google Scholar 

  23. 23.

    Fragkioudaki S, Mavragani CP, Moutsopoulos HM (2016) Predicting the risk for lymphoma development in Sjogren syndrome: an easy tool for clinical use. Medicine 95(25):e3766. https://doi.org/10.1097/md.0000000000003766

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Nocturne G, Virone A, Ng WF, Le Guern V, Hachulla E, Cornec D, Daien C, Vittecoq O, Bienvenu B, Marcelli C, Wendling D, Amoura Z, Dhote R, Lavigne C, Fior R, Gottenberg JE, Seror R, Mariette X (2016) Rheumatoid factor and disease activity are independent predictors of lymphoma in primary Sjogren’s syndrome. Arthritis Rheumatol 68(4):977–985. https://doi.org/10.1002/art.39518

    Article  PubMed  Google Scholar 

  25. 25.

    Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, Sundin U, van Venrooij WJ (2003) Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 48(10):2741–2749. https://doi.org/10.1002/art.11223

    Article  PubMed  Google Scholar 

  26. 26.

    Vencovsky J, Machacek S, Sedova L, Kafkova J, Gatterova J, Pesakova V, Ruzickova S (2003) Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis. Ann Rheum Dis 62(5):427–430

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Berntson L, Nordal E, Fasth A, Aalto K, Herlin T, Nielsen S, Rygg M, Zak M, Ronnelid J (2014) Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA). Pediatr Rheumatol Online J 12(22):22. https://doi.org/10.1186/1546-0096-12-22

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Ramos-Casals M, Brito-Zeron P, Perez DELM, Diaz-Lagares C, Bove A, Soto MJ, Jimenez I, Belenguer R, Siso A, Muxi A, Pons F (2010) Clinical and prognostic significance of parotid scintigraphy in 405 patients with primary Sjogren’s syndrome. J Rheumatol 37(3):585–590. https://doi.org/10.3899/jrheum.090835

    Article  PubMed  Google Scholar 

  29. 29.

    Güne S, Yilmaz S, Karalezli A, Aktas A (2010) Quantitative and visual evaluation of salivary and thyroid glands in patients with primary Sjogren’s syndrome using salivary gland scintigraphy: relationship with clinicopathological features of salivary, lacrimal and thyroid glands. Nucl Med Commun 31(7):666–672

    PubMed  Google Scholar 

  30. 30.

    van Laar JM (2007) Do high levels of IgA rheumatoid factor indicate a poor response to treatment with TNF inhibitors in patients with RA? Nat Clin Pract Rheumatol 3(10):544–545. https://doi.org/10.1038/ncprheum0596

    Article  PubMed  Google Scholar 

  31. 31.

    Markusse HM, Otten HG, Vroom TM, Smeets TJ, Fokkens N, Breedveld FC (1993) Rheumatoid factor isotypes in serum and salivary fluid of patients with primary Sjogren’s syndrome. Clin Immunol Immunopathol 66(1):26–32

    Article  PubMed  Google Scholar 

  32. 32.

    Otten HG, Daha MR, van Laar JM, de Rooy HH, Breedveld FC (1991) Subclass distribution and size of human IgA rheumatoid factor at mucosal and nonmucosal sites. Arthritis Rheum 34(7):831–839

    Article  PubMed  Google Scholar 

  33. 33.

    Garcia-Carrasco M, Ramos-Casals M, Rosas J, Pallares L, Calvo-Alen J, Cervera R, Font J, Ingelmo M (2002) Primary Sjogren syndrome: clinical and immunologic disease patterns in a cohort of 400 patients. Medicine 81(4):270–280

    Article  PubMed  Google Scholar 

  34. 34.

    Koh JH, Lee J, Chung SH, Kwok SK, Park SH (2015) Relation of autoimmune cytopenia to glandular and systemic manifestations in primary Sjogren syndrome: analysis of 113 Korean patients. J Rheumatol 42(10):1817–1824. https://doi.org/10.3899/jrheum.150058

    Article  PubMed  Google Scholar 

  35. 35.

    Zhao Y, Li Y, Wang L, Li XF, Huang CB, Wang GC, Zhang XW, Zhang ZL, Zhang X, Xiao WG, Dai L, Wang YF, Hu SX, Li HB, Gong L, Liu B, Sun LY, Zhang MJ, Zhang X, Li YZ, Du DS, Zhang SH, Sun YY, Zhang FC (2015) Primary Sjogren syndrome in Han Chinese: clinical and immunological characteristics of 483 patients. Medicine 94(16):e667. https://doi.org/10.1097/md.0000000000000667

    Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Atzeni F, Sarzi-Puttini P, Lama N, Bonacci E, Bobbio-Pallavicini F, Montecucco C, Caporali R (2008) Anti-cyclic citrullinated peptide antibodies in primary Sjogren syndrome may be associated with non-erosive synovitis. Arthritis Res Ther 10(3):R51. https://doi.org/10.1186/ar2420

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Kim SM, Park E, Lee JH, Lee SH, Kim HR (2012) The clinical significance of anti-cyclic citrullinated peptide antibody in primary Sjogren syndrome. Rheumatol Int 32(12):3963–3967. https://doi.org/10.1007/s00296-011-2274-3

    Article  PubMed  Google Scholar 

  38. 38.

    ter Borg EJ, Kelder JC (2016) Polyarthritis in primary Sjogren’s syndrome represents a distinct subset with less pronounced B cell proliferation a Dutch cohort with long-term follow-up. Clin Rheumatol 35(3):649–655. https://doi.org/10.1007/s10067-016-3175-3

    Article  PubMed  Google Scholar 

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Funding

This work was funded by the Konkuk University Medical Center Research Grant 2016.

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Correspondence to Sang-Heon Lee.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all the individual participants included in the study.

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Lee, KA., Kim, KW., Kim, BM. et al. Clinical and diagnostic significance of serum immunoglobulin A rheumatoid factor in primary Sjogren’s syndrome. Clin Oral Invest 23, 1415–1423 (2019). https://doi.org/10.1007/s00784-018-2545-4

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Keywords

  • Sjogren’s syndrome
  • Rheumatoid factor
  • IgA rheumatoid factor
  • Diagnosis
  • Exocrine function
  • Extra-glandular manifestations