Adipose tissue is prominent in salivary glands of Sjögren’s syndrome patients and appears to influence the microenvironment in these organs

Abstract

A minor salivary gland (SG) biopsy with focal lymphocytic sialadenitis and a focus score of ≥1 is today's widely accepted pathological finding confirming the SG component of Sjögren's syndrome (SS). Adipocytes can occupy a large percentage of the SG area although little is known about their significance in SS lesions. This study aimed to characterise adipose tissue infiltration in labial SG biopsies from 27 SS patients and 28 non-SS sicca controls. Biopsies were evaluated by one oral pathologist and assessed for focus score, acinar atrophy, fatty replacement and non-specific chronic inflammation. Moreover, to explore the SG microenvironment, immunohistochemical staining of paraffin-embedded SG tissue was performed using interleukin-6 (IL-6). The fatty replacement was evident in all SS patients possessing autoantibodies (Ro/SSA and/or La/SSB) as well as a positive SG biopsy (focus score ≥1). Additionally, 62% of SS patients having autoantibodies but a negative biopsy showed fatty infiltration (FI) while non-SS controls demonstrated fatty replacement in only 32% of the cases. Overall, the SS group (mean age 53.0 years) had a significantly higher incidence (p value 0.005) of FI than the non-SS controls (mean age 54.8 years). Interestingly, adipocytes were located in IL-6 rich areas, and IL-6 positive adipocytes were detected. As fat deposition seems to be more recurrent in SGs affected by SS, we propose the assessment of adipose tissue replacement as a helpful tool for diagnostic evaluation in SS. Detection of IL-6 positive adipocytes suggests their involvement in immune reactions. Still, functional studies are needed to investigate the SG microenvironment further.

Identification of potential saliva and tear biomarkers in primary Sjögren’s syndrome, utilising the extraction of extracellular vesicles and proteomics analysis

“…More precisely, the most upregulated protein in EVs from whole saliva, namely APMAP, is an enzyme central to adipocyte development. We have recently shown increased occurrence of adipose tissue replacement in minor salivary gland biopsies from patients with SS [53]. Interestingly, these adipocytes were detected in areas rich in IL-6, suggesting their active involvement in immune reactions.…”

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

“…A recent study [28] found that SS patients with positive focus scores had a higher incidence of “moderate” and “significant” fatty infiltration, in contrast to largely “negative” nSS. The authors did not define “negative” as the complete absence of adipocytes, but rather as no “significant” presence.…”

“…The subjects in our study had a lower focus score, on average, as compared to their patients (1.5 versus 3.25), which may indicate different disease stages, and could explain the differences in our findings. Of interest, they also reported that adipocytes in pSS tissue produce IL-6, a pro-inflammatory cytokine [28], located away from areas with lymphocytic infiltrates. Our approach examined fatty infiltration as a function of area, allowing increased precision, in addition to a slightly larger study cohort.…”

“…Sub-categorization of primary SS (pSS) types would aid studies seeking to decipher disease mechanisms and help make inroads into understanding disease pathogenesis, which is necessary for development of effective therapeutic approaches. Fatty infiltration is a fundamental form of SG dysmorphism that has been noted [20, 27, 28] but incompletely assessed.…”

Image analysis of fatty infiltration in labial salivary gland biopsies: extent and its correlation to age, obesity and diabetes

“…Most of the studies agree that fatty infiltration is likely to be age‐dependent change suggesting that it has no specific connection to any particular autoimmune diseases or histopathological changes like inflammation ; however, Friedman et al examining several histological changes in MSGs of patients with different autoimmune diseases found that the fibrosis is more common in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), while fatty infiltration was more frequent in rheumatoid arthritis (RA) patients and spared the SSc group. Also, Skarstein et al indicated significantly higher incidence of fatty infiltration in SS than in the control group.…”