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Minor salivary gland fibrosis in Sjögren’s syndrome is elevated, associated with focus score and not solely a consequence of aging

1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15

  1. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF); Department of Pathology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
  2. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
  3. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
  4. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
  5. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
  6. College of Dentistry, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
  7. College of Dentistry, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
  8. Department of Ophthalmology, Johns Hopkins University, Baltimore, MD,USA; and King Khaled Eye Specialist Hospital, Riyadh, KSA.
  9. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF); Department of Pathology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
  10. Division of Oral Medicine and Diagnosis, Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, MN, USA.
  11. Division of Rheumatic and Autoimmune Diseases, University of Minnesota, MN, USA.
  12. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation; Department of Medicine, University of Oklahoma Health Sciences Center; Department of Veteran's Affairs Medical Center, Oklahoma City, OK, USA.
  13. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF); Department of Pathology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
  14. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
  15. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF); Department of Pathology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA. farrisd@omrf.org

CER10325 Submission on line
Full Papers

Rheumatology Article

 

Abstract

OBJECTIVES:
Evaluate the presence of minor salivary gland (SG) fibrosis in primary Sjögren’s syndrome (pSS) as a function of disease pathology or a consequence of ageing.
METHODS:
Subjects with sicca symptoms attending a Sjögren’s research clinic were classified by American European Consensus Group (AECG) criteria as either pSS or non-SS (nSS). Discovery (n=34 pSS, n=28 nSS) and replication (n=35 pSS, n=31 nSS) datasets were evaluated. Minor SG cross-sections from haematoxylin and eosin stained slides were imaged, digitally reconstructed and analysed for percent area fibrosis. Relationships between SG fibrosis, age, and clinical measures were evaluated using Spearman correlations. Association with SS was assessed by: ROC curve, Variable Selection Using Random Forests (VSURF) and uni- and bi-variate regression analyses.
RESULTS:
SS subjects had significantly more fibrotic tissue in their minor labial salivary glands (median 24.39%, range 5.12-51.67%) than nSS participants (median 16.7%, range 5.97-38.65%, p<0.0001); age did not differ between groups (average ± SD pSS 50.2 ±13.9 years, nSS 53.8±12.4 years). In both the discovery and replication data sets, multiple regression models showed that the area of minor salivary gland fibrosis predicted pSS significantly better than age alone. Age-corrected linear regression revealed that the area of minor salivary gland fibrosis positively associated with vanBijsterveld score (p=0.042) and biopsy focus score (p=0.002). ROC curve and VSURF analyses ranked fibrosis as a significantly more important variable for subject discrimination than age.
CONCLUSIONS:
SG fibrosis is an element of pSS pathology that is related to focus score and is not solely attributable to age.

PMID: 29148407 [PubMed]

Received: 14/02/2017 - Accepted : 10/07/2017 - In Press: 23/10/2017