Skip to main content

Advertisement

SpringerLink
Log in

Relationship between retinal morphological findings and autoantibody profile in primary Sjögren’s syndrome

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the morphological changes of the retina measured with the Cirrus high-definition optical coherence tomography in patients with primary Sjögren’s syndrome (pSS).

Methods

One hundred ninety six eyes of 196 patients with pSS and 200 eyes of 200 age and sex-matched normal controls were enrolled. Patients with pSS were divided into four subgroups based on their presence of autoantibodies (antinuclear antibody (ANA), anti-Ro/SSA, and anti-La/SSB). Peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and optic nerve head parameters were compared between groups.

Results

Compared with controls, a significant decrease was observed in the average, inferior, and temporal thicknesses of pRNFL and in the minimum, superotemporal, inferonasal, inferior, and inferotemporal thicknesses of mGCIPL of eyes with pSS (all P < 0.05). In subgroup analyses, all eyes with positive tested autoantibodies [ANA(+), anti-Ro/SSA(+), anti-La/SSB(+)] showed a significant decrease of mGCIPL thicknesses, except for the superonasal portion, compared with eyes with any positivity for autoantibody (all P < 0.05). There was a negative linear relationship between the number of positive autoantibodies and average and inferior pRNFL thicknesses or all mGCIPL parameters, except for the superonasal portion, with a Spearman correlation analysis in patients with pSS (all P < 0.05).

Conclusions

Compared with controls, eyes with pSS showed thinning of pRNFL and mGCIPL thicknesses. The degree of thinning correlated with increased numbers of the positive autoantibody.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet. 2004;363:1711–20.

    Article  PubMed  Google Scholar 

  2. Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:714–20; discussion 829–30.

  3. Tezel G, Yang X, Luo C, Kain AD, Powell DW, Kuehn MH, et al. Oxidative stress and the regulation of complement activation in human glaucoma. Invest Ophthalmol Vis Sci. 2010;51:5071–82.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Grus F, Sun D. Immunological mechanisms in glaucoma. Semin Immunopathol. 2008;30:121–6.

    Article  CAS  PubMed  Google Scholar 

  5. Wax MB, Tezel G. Immunoregulation of retinal ganglion cell fate in glaucoma. Exp Eye Res. 2009;88:825–30.

    Article  CAS  PubMed  Google Scholar 

  6. Cartwright MJ, Grajewski AL, Friedberg ML, Anderson DR, Richards DW. Immune-related disease and normal-tension glaucoma. A case-control study. Arch Ophthalmol. 1992;110:500–2.

    Article  CAS  PubMed  Google Scholar 

  7. Wax MB, Tezel G, Saito I, Gupta RS, Harley JB, Li Z, et al. Anti-Ro/SS-A positivity and heat shock protein antibodies in patients with normal-pressure glaucoma. Am J Ophthalmol. 1998;125:145–57.

    Article  CAS  PubMed  Google Scholar 

  8. Wax MB, Barrett DA, Pestronk A. Increased incidence of paraproteinemia and autoantibodies in patients with normal-pressure glaucoma. Am J Ophthalmol. 1994;117:561–8.

    CAS  PubMed  Google Scholar 

  9. Tezel G, Seigel GM, Wax MB. Autoantibodies to small heat shock proteins in glaucoma. Invest Ophthalmol Vis Sci. 1998;39:2277–87.

    CAS  PubMed  Google Scholar 

  10. Joachim SC, Reichelt J, Berneiser S, Pfeiffer N, Grus FH. Sera of glaucoma patients show autoantibodies against myelin basic protein and complex autoantibody profiles against human optic nerve antigens. Graefes Arch Clin Exp Ophthalmol. 2008;246:573–80.

    Article  CAS  PubMed  Google Scholar 

  11. Grus FH, Joachim SC, Bruns K, Lackner KJ, Pfeiffer N, Wax MB. Serum autoantibodies to alpha-fodrin are present in glaucoma patients from Germany and the United States. Invest Ophthalmol Vis Sci. 2006;47:968–76.

    Article  PubMed  Google Scholar 

  12. Reichelt J, Joachim SC, Pfeiffer N, Grus FH. Analysis of autoantibodies against human retinal antigens in sera of patients with glaucoma and ocular hypertension. Curr Eye Res. 2008;33:253–61.

    Article  CAS  PubMed  Google Scholar 

  13. Gramlich OW, Bell K, von Thun Und Hohenstein-Blaul N, Wilding C, Beck S, Pfeiffer N, et al. Autoimmune biomarkers in glaucoma patients. Curr Opin Pharmacol. 2013;13:90–7.

    Article  CAS  PubMed  Google Scholar 

  14. Joachim SC, Bruns K, Lackner KJ, Pfeiffer N, Grus FH. Antibodies to alpha B-crystallin, vimentin, and heat shock protein 70 in aqueous humor of patients with normal tension glaucoma and IgG antibody patterns against retinal antigen in aqueous humor. Curr Eye Res. 2007;32:501–9.

    Article  CAS  PubMed  Google Scholar 

  15. Joachim SC, Pfeiffer N, Grus FH. Autoantibodies in patients with glaucoma: a comparison of IgG serum antibodies against retinal, optic nerve, and optic nerve head antigens. Graefes Arch Clin Exp Ophthalmol. 2005;243:817–23.

    Article  CAS  PubMed  Google Scholar 

  16. Grus FH, Joachim SC, Hoffmann EM, Pfeiffer N. Complex autoantibody repertoires in patients with glaucoma. Mol Vis. 2004;10:132–7.

    CAS  PubMed  Google Scholar 

  17. Laspas P, Gramlich OW, Muller HD, Cuny CS, Gottschling PF, Pfeiffer N, et al. Autoreactive antibodies and loss of retinal ganglion cells in rats induced by immunization with ocular antigens. Invest Ophthalmol Vis Sci. 2011;52:8835–48.

    Article  CAS  PubMed  Google Scholar 

  18. Wax MB, Tezel G, Yang J, Peng G, Patil RV, Agarwal N, et al. Induced autoimmunity to heat shock proteins elicits glaucomatous loss of retinal ganglion cell neurons via activated T-cell-derived fas-ligand. J Neurosci. 2008;28:12085–96.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Mwanza JC, Oakley JD, Budenz DL, Chang RT, Knight OJ, Feuer WJ. Macular ganglion cell-inner plexiform layer: automated detection and thickness reproducibility with spectral domain-optical coherence tomography in glaucoma. Invest Ophthalmol Vis Sci. 2011;52:8323–9.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Mwanza JC, Durbin MK, Budenz DL, Sayyad FE, Chang RT, Neelakantan A, et al. Glaucoma diagnostic accuracy of ganglion cell-inner plexiform layer thickness: comparison with nerve fiber layer and optic nerve head. Ophthalmology. 2012;119:1151–8.

    Article  PubMed  Google Scholar 

  21. Takayama K, Hangai M, Durbin M, Nakano N, Morooka S, Akagi T, et al. A novel method to detect local ganglion cell loss in early glaucoma using spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2012;53:6904–13.

    Article  PubMed  Google Scholar 

  22. Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61:554–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Ramos-Casals M, Font J. Primary Sjogren’s syndrome: current and emergent aetiopathogenic concepts. Rheumatology (Oxford). 2005;44:1354–67.

    Article  CAS  Google Scholar 

  24. Ramos-Casals M, Cervera R, Font J, Garcia-Carrasco M, Espinosa G, Reino S, et al. Young onset of primary Sjogren’s syndrome: clinical and immunological characteristics. Lupus. 1998;7:202–6.

    Article  CAS  PubMed  Google Scholar 

  25. Ramos-Casals M, Font J, Garcia-Carrasco M, Brito MP, Rosas J, Calvo-Alen J, et al. Primary Sjogren syndrome: hematologic patterns of disease expression. Medicine (Baltimore). 2002;81:281–92.

    Article  PubMed  Google Scholar 

  26. Locht H, Pelck R, Manthorpe R. Clinical manifestations correlated to the prevalence of autoantibodies in a large (n = 321) cohort of patients with primary Sjogren’s syndrome: a comparison of patients initially diagnosed according to the Copenhagen classification criteria with the American-European consensus criteria. Autoimmun Rev. 2005;4:276–81.

    Article  CAS  PubMed  Google Scholar 

  27. Shah F, Rapini RP, Arnett FC, Warner NB, Smith CA. Association of labial salivary gland histopathology with clinical and serologic features of connective tissue diseases. Arthritis Rheum. 1990;33:1682–7.

    Article  CAS  PubMed  Google Scholar 

  28. Hammam T, Montgomery D, Morris D, Imrie F. Prevalence of serum autoantibodies and paraproteins in patients with glaucoma. Eye (Lond). 2008;22:349–53.

    Article  CAS  PubMed  Google Scholar 

  29. Wax MB. The case for autoimmunity in glaucoma. Exp Eye Res. 2011;93:187–90.

    Article  CAS  PubMed  Google Scholar 

  30. Savitz DA, Olshan AF. Multiple comparisons and related issues in the interpretation of epidemiologic data. Am J Epidemiol. 1995;142:904–8.

    CAS  PubMed  Google Scholar 

  31. Gelman A, Hill J, Yajima M. Why we (usually) don’t have to worry about multiple comparisons. J Res Educ Eff. 2012;5:189–211.

    Google Scholar 

  32. Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiology. 1990;1:43–6.

    Article  CAS  PubMed  Google Scholar 

  33. Grus FH, Joachim SC, Wuenschig D, Rieck J, Pfeiffer N. Autoimmunity and glaucoma. J Glaucoma. 2008;17:79–84.

    Article  PubMed  Google Scholar 

  34. Schwartz M. Neurodegeneration and neuroprotection in glaucoma: development of a therapeutic neuroprotective vaccine: the Friedenwald lecture. Invest Ophthalmol Vis Sci. 2003;44:1407–11.

    Article  PubMed  Google Scholar 

  35. Ambrosi A, Wahren-Herlenius M. Congenital heart block: evidence for a pathogenic role of maternal autoantibodies. Arthritis Res Ther. 2012;14:208.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Clancy RM, Neufing PJ, Zheng P, O’Mahony M, Nimmerjahn F, Gordon TP, et al. Impaired clearance of apoptotic cardiocytes is linked to anti-SSA/Ro and -SSB/La antibodies in the pathogenesis of congenital heart block. J Clin Invest. 2006;116:2413–22.

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Rosen A, Casciola-Rosen L, Ahearn J. Novel packages of viral and self-antigens are generated during apoptosis. J Exp Med. 1995;181:1557–61.

    Article  CAS  PubMed  Google Scholar 

  38. Lucas M, Stuart LM, Savill J, Lacy-Hulbert A. Apoptotic cells and innate immune stimuli combine to regulate macrophage cytokine secretion. J Immunol. 2003;171:2610–5.

    Article  CAS  PubMed  Google Scholar 

  39. Gaipl US, Munoz LE, Grossmayer G, Lauber K, Franz S, Sarter K, et al. Clearance deficiency and systemic lupus erythematosus (SLE). J Autoimmun. 2007;28:114–21.

    Article  PubMed  Google Scholar 

  40. Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ. Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci. 1995;36:774–86.

    CAS  PubMed  Google Scholar 

  41. Hernandez-Molina G, Leal-Alegre G, Michel-Peregrina M. The meaning of anti-Ro and anti-La antibodies in primary Sjogren’s syndrome. Autoimmun Rev. 2011;10:123–5.

    Article  CAS  PubMed  Google Scholar 

  42. Asmussen K, Andersen V, Bendixen G, Schiodt M, Oxholm P. A new model for classification of disease manifestations in primary Sjogren’s syndrome: evaluation in a retrospective long-term study. J Intern Med. 1996;239:475–82.

    Article  CAS  PubMed  Google Scholar 

  43. ter Borg EJ, Risselada AP, Kelder JC. 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. 2011;40:547–51.

    Article  PubMed  Google Scholar 

  44. Manoussakis MN, Tzioufas AG, Pange PJ, Moutsopoulos HM. Serological profiles in subgroups of patients with Sjogren’s syndrome. Scand J Rheumatol Suppl. 1986;61:89–92.

    CAS  PubMed  Google Scholar 

  45. Cheung CY, Leung CK, Lin D, Pang CP, Lam DS. Relationship between retinal nerve fiber layer measurement and signal strength in optical coherence tomography. Ophthalmology. 2008;115:1347–51, 51 e1–2.

  46. Wu Z, Vazeen M, Varma R, Chopra V, Walsh AC, LaBree LD, et al. Factors associated with variability in retinal nerve fiber layer thickness measurements obtained by optical coherence tomography. Ophthalmology. 2007;114:1505–12.

    Article  PubMed  Google Scholar 

  47. Lee ES, Kim NR, Seong GJ, Hong S, Kim CY. Effect of signal strength on agreements for retinal nerve fiber layer thickness measurement and its color code classification between Stratus and Cirrus optical coherence tomography. J Glaucoma. 2011;20:371–6.

    Article  CAS  PubMed  Google Scholar 

  48. Wu Z, Huang J, Dustin L, Sadda SR. Signal strength is an important determinant of accuracy of nerve fiber layer thickness measurement by optical coherence tomography. J Glaucoma. 2009;18:213–6.

    Article  PubMed  Google Scholar 

  49. Elkon KB, Gharavi AE, Hughes GR, Moutsoupoulos HM. Autoantibodies in the sicca syndrome (primary Sjogren’s syndrome). Ann Rheum Dis. 1984;43:243–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Conflicts of interest

J. M. Yang, None; H. Heo, None; S. W. Park, None.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Chonnam National University Medical School and Hospital, 8 Hak-Dong, Dong-Gu, Gwangju, 501-757, South Korea

    Jee Myung Yang, Hwan Heo & Sang Woo Park

  2. Center for Creative Biomedical Scientists, Chonnam National University, Gwangju, South Korea

    Sang Woo Park

Authors
  1. Jee Myung Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hwan Heo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sang Woo Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sang Woo Park.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, J.M., Heo, H. & Park, S.W. Relationship between retinal morphological findings and autoantibody profile in primary Sjögren’s syndrome. Jpn J Ophthalmol 58, 359–368 (2014). https://doi.org/10.1007/s10384-014-0327-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-014-0327-3

Keywords

Search

Navigation