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

K. M. Leehan, N. P. Pezant, A. Rasmussen, K. Grundahl, J. S. Moore, L. Radfar, D. M. Lewis, D. U. Stone, C. J. Lessard, Nelson L Rhodus, B. M. Segal, R. H. Scofield, K. L. Sivils, C. Montgomery, A. D. Farris

Research output: Contribution to journalArticle

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Abstract

Objective. 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 uniand 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. Conclusion. SG fibrosis is an element of pSS pathology that is related to focus score and is not solely attributable to age.

Original languageEnglish (US)
Pages (from-to)S80-S88
JournalClinical and Experimental Rheumatology
Volume36
StatePublished - Jan 1 2018

Fingerprint

Minor Salivary Glands
Fibrosis
Salivary Glands
ROC Curve
Ageism
Pathology
Hematoxylin
Eosine Yellowish-(YS)
Lip
Linear Models
Consensus
Regression Analysis
Biopsy
Research

Keywords

  • Aging
  • Fibrosis
  • Focus score
  • Minor salivary gland
  • Sjögren's syndrome

Cite this

Leehan, K. M., Pezant, N. P., Rasmussen, A., Grundahl, K., Moore, J. S., Radfar, L., ... Farris, A. D. (2018). Minor salivary gland fibrosis in Sjögren's syndrome is elevated, associated with focus score and not solely a consequence of aging. Clinical and Experimental Rheumatology, 36, S80-S88.

Minor salivary gland fibrosis in Sjögren's syndrome is elevated, associated with focus score and not solely a consequence of aging. / Leehan, K. M.; Pezant, N. P.; Rasmussen, A.; Grundahl, K.; Moore, J. S.; Radfar, L.; Lewis, D. M.; Stone, D. U.; Lessard, C. J.; Rhodus, Nelson L; Segal, B. M.; Scofield, R. H.; Sivils, K. L.; Montgomery, C.; Farris, A. D.

In: Clinical and Experimental Rheumatology, Vol. 36, 01.01.2018, p. S80-S88.

Research output: Contribution to journalArticle

Leehan, KM, Pezant, NP, Rasmussen, A, Grundahl, K, Moore, JS, Radfar, L, Lewis, DM, Stone, DU, Lessard, CJ, Rhodus, NL, Segal, BM, Scofield, RH, Sivils, KL, Montgomery, C & Farris, AD 2018, 'Minor salivary gland fibrosis in Sjögren's syndrome is elevated, associated with focus score and not solely a consequence of aging' Clinical and Experimental Rheumatology, vol. 36, pp. S80-S88.
Leehan, K. M. ; Pezant, N. P. ; Rasmussen, A. ; Grundahl, K. ; Moore, J. S. ; Radfar, L. ; Lewis, D. M. ; Stone, D. U. ; Lessard, C. J. ; Rhodus, Nelson L ; Segal, B. M. ; Scofield, R. H. ; Sivils, K. L. ; Montgomery, C. ; Farris, A. D. / Minor salivary gland fibrosis in Sjögren's syndrome is elevated, associated with focus score and not solely a consequence of aging. In: Clinical and Experimental Rheumatology. 2018 ; Vol. 36. pp. S80-S88.
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abstract = "Objective. Evaluate the presence of minor salivary gland (SG) fibrosis in primary Sj{\"o}gren's syndrome (pSS) as a function of disease pathology or a consequence of ageing. Methods. Subjects with sicca symptoms attending a Sj{\"o}gren'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 uniand 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. Conclusion. SG fibrosis is an element of pSS pathology that is related to focus score and is not solely attributable to age.",
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AU - Pezant, N. P.

AU - Rasmussen, A.

AU - Grundahl, K.

AU - Moore, J. S.

AU - Radfar, L.

AU - Lewis, D. M.

AU - Stone, D. U.

AU - Lessard, C. J.

AU - Rhodus, Nelson L

AU - Segal, B. M.

AU - Scofield, R. H.

AU - Sivils, K. L.

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