2.3.4. Sjögren Syndrome
Sjögren syndrome is an autoimmune disease with a strong negative impact on the quality of life of affected people. The main features of the disease are lymphocytic inflammation and alterations in major salivary glands, causing xerostomia [103]. Even if preliminary results about HCQ use in Sjögren syndrome were not encouraging, to date it arises as one of the first-line drugs in disease treatment. Indeed, an earlier prospective, a two-year double-blind crossover trial on 19 subjects correlated an annual intake of a dose of 400 mg/day with no significant improvements in clinical symptoms and signs of pathology, including tear and salivary gland activity, respect to the placebo [121]. However, a few years later, the first evidence of HCQ effectiveness in Sjögren syndrome treatment was reported. Annual treatment with a dose of 200 mg/day of HCQ showed anti-lymphoproliferative and anti-inflammatory effects, with a reduction of IgG and IgA immunoglobulins, anti-Sjögren autoantibodies, and erythrocyte sedimentation rates [100]. Moreover, the salivary flow rate increased in Sjögren syndrome women who received a daily dose of 400 mg of HCQ for 30 weeks [101], while eye dryness was alleviated by HCQ administration (6.5 mg/kg), as demonstrated by a prospective study on 32 patients [102]. Hypo-salivation deriving from acinar atrophy and fibrosis of salivary glands is often associated with over-expression of TGF-β (transforming growth factor-β). Treatment with HCQ downregulated TGF-β levels in a randomized trial on NOD mice exposed to doses of 50 mg/kg/day intragastrically (i.g.) for 16 weeks, with significant results in delaying loss of saliva secretory function. Moreover, HCQ intake was also accompanied by a decrease in autoantibody production and a lower lymphocytic infiltration [103]. These findings were confirmed by Wu, Pu, Yu and Li [104], showing that 8-weeks treatment with HCQ administered at a dose of 60 mg/kg i.g. in 40 randomized NOD mice led to lower lymphocytic infiltration, with a significant improvement in pathological changes in submandibular gland morphology.