What about glucocorticoids in primary Sjögren's syndrome?

Glucocorticoids (GCs) are involved in several physiological processes such as metabolism, water and electrolyte balance, growth, cardiovascular and cognitive functions, reproduction. Furthermore, they exert different effects on innate and adaptive immune cells. Due to their anti-inflammatory and immunosuppressive functions, these drugs are largely used for the treatment of inflammatory and autoimmune diseases. In comparison to other autoimmune rheumatic diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), to date no reliable evidence is available for the use of systemic GCs in Sjögren's syndrome (SS), which is still based on case reports, case studies, retrospective or prospective studies and a small number of randomised controlled trials (RCTs). Despite this gap in our knowledge, GCs are commonly used in SS for glandular, joint, cutaneous, lung, haematological, renal, neurological involvement. More recently, some sets of recommendations for the management of SS have provided a few pieces of advice regarding the use of GCs in this condition. Future studies should not neglect the role of GCs, as this traditional therapeutic weapon can still have a role in the management of SS. Accordingly, this review will address and discuss the use of systemic GCs in isolated or primary SS.

Immunohistochemical detection of IL-17 and IL-23 improves the identification of patients with a possible diagnosis of Sjogren's syndrome.

OBJECTIVES: The diagnosis of primary Sjogren's syndrome (pSS) continues to be difficult and several patients keep symptomatic for years with different diagnoses before confirmation of pSS. Since the IL-23-IL-17 axis is involved in the etiopathogenesis of pSS we evaluated by immunohistochemistry and morphometric methods the presence of IL-17 as well as IL-23 within minor salivary glands (MSG) obtained from patients with uncertain diagnosis of pSS. MATERIALS AND METHODS: 42 patients, with symptoms attributable to pSS, and 8 patients used as a control, were enrolled for the study. Autoantibody detection, histological analysis for the presence of Germinal Centers (GC+), immunohistochemistry to detect IL-23 and IL-17 were performed. RESULTS: The detection of GC + anti-SSA and anti-SSB antibody in parallel with the detection of IL-17 and IL-23, displays only a diagnostic reinforcement value. Instead, the detection of a positive reaction for both IL-17 and IL-23 without GC + or autoantibody within minor salivary glands, as detected in 36 % of patients with uncertain diagnosis, may be hold as a sensitive and specific marker to identify those patients who are likely to evolve into pSS. CONCLUSION: we suggest to use the IL-17/ IL-23 immunohistochemical detection to improve the identification of patients with a possible diagnosis in all cases which do not fully meet the American-European criteria for pSS, in particular when the GC + are not present at histopathological analysis and anti-SSA and anti-SSB antibody are undetectable in the serum.

Autophagy occurs in lymphocytes infiltrating Sjögren's syndrome minor salivary glands and correlates with histological severity of salivary gland lesions.

BACKGROUNDS: The organization of minor salivary glands (MSG) infiltrates, in patients with Sjögren's syndrome (SS), associates with disease severity and progression. Aberrant regulation of lymphocyte autophagy is involved in autoimmunity, and in previous work, we provided the first evidence of upregulated autophagy in CD4+ T cells infiltrating SS MSG. The aim of this study was to further explore autophagy in SS infiltrating and circulating lymphocytes and to investigate its role in disease histopathological progression. METHODS: After collection of 20 SS MSG, the presence of lymphocyte aggregates (foci) and the formation of germinal center (GC)-like structures were observed by H&E and confirmed by immunohistochemistry. The expression of autophagy-related genes, Atg5 and MAP1LC3A, was detected by RT-PCR on microdissected salivary gland tissue and control tonsils. In MSG and tonsils, autophagic lymphocytes were identified by the detection of the autophagosome protein LC3B visualized as LC3 puncta staining by immunofluorescence. Peripheral blood autophagy was assessed by flow cytometry in SS and healthy controls (HC). RESULTS: Real-time PCR demonstrated higher expression in the autophagy genes Atg5 and MAP1LC3A in MSG GCs as compared to both small foci (p = 0.0075, p = 0.0002) and GCs from tonsils (p = 0.0001, p = 0.0037). In MSG, LC3 puncta staining was detectable on both CD3+ and CD20+ lymphocytes; in tonsils, LC3 puncta was almost undetectable on all lymphocytes. Compared to HC (n = 20), flow cytometry did not reveal any increase of autophagy in SS circulating lymphocytes (n = 30). CONCLUSIONS: In SS MSG, lymphocytes' autophagy is a feature of infiltrating T and B cells and is associated with histological severity. Interestingly, in MSG aberrant regulation of autophagy is detectable in GC-like structures possibly indicating its involvement in the development and persistence of the autoimmune process within the lesions.