Investigation of three potential autoantibodies in Sjogren's syndrome and associated MALT lymphoma

Oncotarget. 2017 May 2;8(18):30039-30049. doi: 10.18632/oncotarget.15613.

Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease which might progress to mucosal-associated lymphoid tissue lymphoma (pSS/MALT). Diagnosis of pSS requires an invasive tissue biopsy and a delay in diagnosis of pSS has been frequently reported. In this study, four proteins including cofilin-1, alpha-enolase, annexin A2 and Rho GDP-dissociation inhibitor 2 (RGI2) were found to be over-expressed in pSS and pSS/MALT by 2D gel electrophoresis/mass spectrometry, and the finding was verified by the microarray analysis and western blotting results. We then developed enzyme-linked immunosorbent assays for autoantibodies including anti-cofilin-1, anti-alpha-enolase and anti-RGI2 with good quantitative ability. The expression levels of salivary anti-cofilin-1, anti-alpha-enolase and anti-RGI2 were found to be the highest in pSS/MALT patients and lowest in healthy controls. The combination of these three antiantibodies yielded an "area under the curve" (AUC) value of 0.94 with an 86% sensitivity and 93% specificity in distinguishing patients with pSS from healthy controls, an AUC value of 0.99 with a 95% sensitivity and 94% specificity in distinguishing patients with pSS/MALT from healthy controls and an AUC value of 0.86 with a 75% sensitivity and 94% specificity in distinguishing pSS/MALT patients from pSS patients. Collectively, we have successfully identified a panel of potential autoantigens that are progressively up-regulated during the development of pSS and its progression to MALT lymphoma. The autoantibody biomarkers may be used to help diagnose pSS and predict its progression to MALT lymphoma.

Keywords: Rho GDP-dissociation inhibitor 2; alpha-enolase; cofilin-1; mucosal-associated lymphoid tissue lymphoma; primary Sjögren’s syndrome.

MeSH terms

  • Autoantibodies / immunology*
  • Autoantigens / immunology
  • Biomarkers
  • Case-Control Studies
  • Electrophoresis, Gel, Two-Dimensional
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Lymphoma, B-Cell, Marginal Zone / diagnosis
  • Lymphoma, B-Cell, Marginal Zone / etiology*
  • Male
  • Mass Spectrometry
  • Prognosis
  • Proteomics / methods
  • ROC Curve
  • Reproducibility of Results
  • Saliva / immunology
  • Sjogren's Syndrome / blood
  • Sjogren's Syndrome / complications*
  • Sjogren's Syndrome / diagnosis
  • Sjogren's Syndrome / immunology*

Substances

  • Autoantibodies
  • Autoantigens
  • Biomarkers