Fatty infiltration of the minor salivary glands is a selective feature of aging but not Sjögren’s syndrome

Abstract

Objective Determine the presence and assess the extent of fatty infiltration of the minor salivary glands (SG) of primary SS patients (pSS) as compared to those with non SS sicca (nSS). Methods Minor SG biopsy samples from 134 subjects with pSS (n= 72) or nSS (n = 62) were imaged. Total area and fatty replacement area for each glandular cross-section (n=4–6 cross-sections per subject) were measured using Image J (National Institutes of Health, Bethesda, MD, USA). The observer was blinded to subject classification status. The average area of fatty infiltration calculated per subject was evaluated by logistic regression and general linearized models (GLM) to assess relationships between fatty infiltration and clinical exam results, extent of fibrosis and age. Results The average area of fatty infiltration for subjects with pSS (median% (range) 4.97 (0.05–30.2)) was not significantly different from that of those with nSS (3.75 (0.087–41.9). Infiltration severity varied widely, and subjects with fatty replacement greater than 6% were equivalently distributed between pSS and nSS participants (χ2 p=0.50). Age accounted for all apparent relationships between fatty infiltration and fibrosis or reduced saliva flow. The all-inclusive GLM for prediction of pSS versus non-SS classification including fibrosis, age, fatty replacement and focus score was not significantly different from any desaturated model. In no iteration of the model did fatty replacement exert a significant effect on the capacity to predict pSS classification. Conclusions Fatty infiltration is an age-associated phenomenon and not a selective feature of Sjögren’s syndrome. Sicca patients who do not fulfill pSS criteria have similar rates of fatty infiltration of the minor SG.

Current concepts on Sjögren's syndrome – classification criteria and biomarkers

“…Our own studies indicated a higher incidence of adipose tissue in the salivary glands of patients with Sjögren's syndrome compared with non‐Sjögren's syndrome controls . However, others suggest that fatty infiltration can be a selective feature of ageing rather than disease . Regardless, adipocytes may be active players in immune reactions because adipocytes have been localized in certain cytokine‐ and chemokine‐rich niches of salivary glands from patients with Sjögren's syndrome .…”

Imaging in Primary Sjögren’s Syndrome

“…In addition to these characteristic features, proportions of fibrosis and acinar atrophy within salivary gland tissue are higher in pSS patients compared to controls [ 21 , 22 ]. There is no agreement yet whether fatty infiltration is age-associated or specific for pSS [ 23 , 24 ]. Besides their role in the diagnostic work-up of pSS, biopsies may also be used to assess prognosis ( Table 2 ).…”

Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren’s syndrome condition

“…The oral and salivary manifestations observed in pSS include dry mouth, difficulty in chewing and swallowing food, and oral burning symptoms [5][6][7]. Importantly, clinical manifestations from primary pSS patients and animal models of SS point to the loss of salivary gland function that results from abnormal autoimmune response; however, the mechanism that initiates loss of salivary gland secretion is not well understood [8,9]. Extra glandular manifestations are also common for these patients, who show an enhanced lymphoproliferation, with a greater risk of forming malignant lymphoma.…”

“…Extra glandular manifestations are also common for these patients, who show an enhanced lymphoproliferation, with a greater risk of forming malignant lymphoma. Histologically, pSS is characterized by extensive lymphocytic infiltration that is observed in the salivary and lacrimal gland tissues [8][9][10][11][12] and secretion of proteases, such as serine proteases, could induce the loss of salivary glands. Importantly, salivary gland cells have a measure that can protect them against the proteases secreted by immune cells; however, if these protective mechanisms are lost, they may induce cell death [9,13,14].…”