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Immune cell-mediated destruction of salivary glands is a hallmark feature of Sjögren syndrome. Similar to the female predominance in humans, female non-obese diabetic (NOD) mice develop spontaneous salivary gland autoimmunity. However, in both humans and mice it is unclear what factors contribute to the initial immune infiltration of the salivary glands. Here, we used an adoptive transfer model of Sjögren syndrome to determine if female mice harbor a sex-specific defect in salivary-gland-protective regulatory T (Treg) cells. Transfer of cervical lymph node (LN) cells from female NOD mice into sex-matched NOD-severe combined immunodeficient (SCID) recipients resulted in sialadenitis, regardless of the presence or absence of Treg cells. In contrast, transfer of cervical LN cells from male NOD mice into sex-matched NOD-SCID recipients only resulted in sialadenitis when Treg cells were depleted before transfer, suggesting that male NOD mice have functional salivary-gland-protective Treg cells. Notably, the host environment affected the ability of Treg cells to prevent sialadenitis with testosterone promoting salivary gland protection. Treg cells from male mice did not protect against sialadenitis in female recipients. Testosterone treatment of female recipients of bulk cervical LN cells decreased sialadenitis, and Treg cells from female mice were capable of protecting against development of sialadenitis in male recipients. Hence, our data demonstrate that female NOD mice develop sialadenitis through a defect in salivary-gland-protective Treg cells that can be reversed in the presence of testosterone., (© 2018 John Wiley & Sons Ltd.)

Objectives: To evaluate the effectiveness of interventional sialendoscopy alone or combined with outpatient intraductal steroid irrigations in patients with sialadenitis due to Sjögren's syndrome (SS)., Design: A pilot therapeutic study., Setting: ENT Clinics, Universities of Milan and Pavia., Study Population: We included 22 patients with SS of whom 12 underwent interventional sialendoscopy followed by intraductal steroid irrigations (group A), and 10 interventional sialendoscopy alone (group B)., Outcomes Measures: The following outcome measures were considered and recorded before and after the therapeutic intervention: (i) number of episodes of glandular swelling, (ii) cumulative prevalence of patients with glandular swelling assessed by the specific domain, the EULAR SS Disease Activity Index (ESSDAI), (iii) severity of pain by means of a 0-10 pain visual analogue scale (VAS), (iv) severity of xerostomia and other disease symptoms assessed by the EULAR SS Patient Reported Index (ESSPRI) and the Xerostomia Inventory questionnaire., Results: The postoperative reduction in the mean number of episodes of glandular swelling was 87% (95% CI: 77-93) and 75% (95% CI: 47%-88%) in the groups A and B, respectively. The percentage of patients with glandular swelling decreased from 41.7% to 0.0% in the group A and from 30.0% to 0.0% in the group B, respectively. Most of the patients experienced a subjective clinical improvement documented by the statistically significant reductions in the postoperative mean pain VAS (group A P<.001; group B P=.004), Xerostomia Inventory (P<.001 and P=.003) and ESSPRI scores (P<.001 and P=.008). Interventional sialendoscopy followed by outpatient intraductal steroid irrigations was more effective than interventional sialendoscopy alone, when pain VAS, Xerostomia Inventory and ESSPRI scores before and after treatment were analysed together using the multivariate Hotelling T 2 test (P=.0173)., Conclusions: This pilot study confirms that interventional sialendoscopy with steroid duct irrigation significantly reduces the number of painful episodes of sialadenitis and improves the subjective sensation of oral dryness and other disease symptoms in patients with SS. The study results also suggest that the improvement is greater when interventional sialendoscopy is combined with a cycle of outpatient steroid ductal irrigations. Larger controlled randomised studies are certainly needed to confirm these preliminary data., (© 2017 John Wiley & Sons Ltd.)

Aims: We report uncommon histopathological findings in fatal measles infection., Methods and Results: We describe the autopsies of four patients who died during a measles outbreak in São Paulo, Brazil, in 1997. Two of the patients were children receiving chemotherapy for non-Hodgkin's lymphoma, one was an adult with acquired immunodeficiency syndrome (AIDS) and the fourth was an apparently healthy woman. All patients had their deaths attributed to measles pneumonia. The autopsies revealed extensive giant cell pneumonia and diffuse alveolar damage, severe acute pancreatitis, necrotizing sialoadenitis and thyroiditis due to measles. Measles antigen was detected in lung tissue using a monoclonal anti-measles antibody., Conclusions: : Pancreatitis, thyroiditis and sialoadenitis are not previously reported histopathological findings in measles infection. Pancreatitis is a potentially severe complication and should be considered when treating patients with atypical measles.

Aims: Confusion about the aetiology and pathogenesis of chronic submandibular sialadenitis led to the present investigation of 154 cases in which many clinical and histological features were analysed., Methods and Results: By far the greatest number of histological factors, namely liths, atrophy, fibrosis, parenchymal inflammation, lymphoid germinal centres, mucous and ciliary metaplasia, salivary extravasation and glycosaminoglycan accumulation, was related to the degree of inflammation, which appears to be of the greatest importance in the aetiology and pathogenesis. Inflammation, atrophy and fibrosis were related to duration of symptoms, which supports the concept of a chronological progression through increasingly severe histological changes., Conclusions: Inflammation possibly arises from ascending infection in a normal gland and exerts an obstructive and destructive effect on the parenchyma with the development of the related histological changes and a vicious circle involving further ascending infection. Normal glands contain microliths that possibly by localized obstruction cause atrophic foci that are reservoirs for ascending infection. Microliths and liths were unrelated: microliths were related to age as in normal glands whereas liths were related to duration of symptoms and appeared to be secondary to the sialadenitis. Many glands showed minimal changes, which raises the possibility of conservative treatment.

Recently we showed that not only homozygous MRL lpr/lpr mice but also heterozygous MRL +/lpr mice display defective antigen- and mitogen-driven T-cell responses as well as polyclonal B-cell activation compared with congeneic MRL +/+ mice. In this study we examined the impact of the heterozygous lpr gene on organ pathology in kidneys, joints, and salivary glands, as well as serum levels of immunoglobulins and autoantibodies in young and old MRL mice. Only 1 out of 17 heterozygous lpr-bearing MRL mice developed clinically overt renal disease with significant proteinuria and haematuria during the first year of life. However, examination of Ig and C3 deposits in glomeruli of kidneys from these mice revealed that the expression of the heterozygous lpr gene in MRL mice accelerates glomerulonephritis. In addition, histological examination of the submandibular salivary glands showed an increased focus score in heterozygous MRL mice at 4-5 months of age compared with that of matched congeneic +/+ mice. In contrast, no signs of arthropathy were registered in the heterozygous lpr-bearing MRL mice. Heterozygous MRL mice displayed an expanding lymphoid system as evaluated by significantly increased spleen and lymph node weights compared with those of matched MRL +/+ mice. Further evidence for immunomodulatory properties of the heterozygous lpr gene was obtained when analysing serum levels of IgG, IgM, and autoantibodies. Thus, heterozygous MRL +/lpr mice produced significantly higher levels of both Ig and autoantibodies than matched MRL +/+ mice. We conclude that the expression of the heterozygous lpr gene in MRL mice results in acceleration of the autoimmune process, giving rise to precocious clinical disease.

Fifty-seven of 469 major salivary glands excised for various reasons were found to contain granulomas. The aetiologies were tuberculosis (eight parotid, one sublingual), sarcoidosis (two parotid), calculous duct obstruction (34 submandibular), carcinomatous duct obstruction (four submandibular, one sublingual) and undetermined (four submandibular, three parotid). The tuberculous glands showed caseation in the majority of cases but two cases consisted predominantly of discrete granulomas with minimal necrosis. The sarcoid granulomas were typically non-caseating but a few were centrally necrotic. The cases of calculous and carcinomatous duct obstruction contained single to multiple small granulomas which contained mucin and were related to ruptured ducts. It is suggested that the frequency of calculi and the mixture of serous and mucous acini in the submandibular gland account for the distribution of obstructive granulomas. This study establishes calculous sialadenopathy as a major cause of granulomatous sialadenitis.

During 1960-1975, 115 submandibular glands were removed for reasons other than neoplasia at the Ear, Nose and Throat department, Karolinska sjukhuset, Stockholm. The material was retrospectively analysed with regard to clinical and histopathological findings. The patients, 62 men and 52 women aged 13-77 years, exhibited in all cases but one a chronic sialadenitis. Salivary calculi were found in 82% of the patients. In one patient a mucous retention cyst was found. Microscopically some cases exhibited only a slight periductal inflammation, while others showed a complete destruction of the gland architecture. The duration of symptoms of the whole group before surgery varied from 1 week to 55 years but with a median value of almost 1 year. The conclusion of this study is that salivary calculus is the most important indication for removal of submandibular gland, for reasons other than neoplasia.