Iguratimod in treatment of primary Sjögren’s syndrome concomitant with autoimmune hemolytic anemia:A case report

BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.However,there are few reports about the application of IGU in pSS concomitant with AIHA.CASE SUMMARY Here,we present the case of a patient with pSS concomitant with AIHA but without eye and mouth dryness.The patient was initially diagnosed with hyperplastic anemia and AIHA while pSS was missed,and was finally diagnosed with pSS concomitant with AIHA.The patient was treated with IGU along with prednisone and hydroxychloroquine,and her hemoglobin,reticulocytes and IgG returned to normal levels.CONCLUSION IGU was effective for and well tolerated by our patient with pSS concomitant with AIHA,and may be a promising therapy for the treatment of this disease.

AA Amyloidosis Secondary to Primary Sjögren Syndrome: Can It Be Developed without Chronic Inflammation?

Background: The association of primary Sjögren syndrome (PSS) and AA amyloidosis is a rare occurrence. Objective: To describe the phenotype of patients with this association through our two cases and a literature review. Materials and methods: A report of two cases of AA amyloidosis complicating primary Sjögren syndrome with a literature review. Results: Eight patients of Primary Sjögren’s Syndrome complicated by AA amyloidosis were studies. Six cases were reported in the literature by consulting several databases. 50% of patients had a positive immunological assessment, three cases with kidney damage, and three cases lung damage. Conclusion: The immunological activity in the Primary Sjogren’s Syndrome requires the search not only a lymphoma but also AA amyloidosis apart from any clinical or biological chronic inflammation.

Role of JAK-STAT signaling pathway in pathogenesis and treatment of primary Sjögren’s syndrome

Primary Sjögren’s syndrome(pSS)is a systemic autoimmune disease with high prevalence and possible poor prognosis.Though the pathogenesis of pSS has not been fully elucidated,B cell hyperactivity is considered as one of the fundamental abnormalities in pSS patients.It has long been identified that Janus kinases-signal transducer and activator of transcription(JAK-STAT)signaling pathway contributes to rheumatoid arthritis and systemic lupus erythematosus.Recently,increasing numbers of studies have provided evidence that JAK-STAT pathway also has an important role in the pathogenesis of pSS via direct or indirect activation of B cells.Signal transducer and activator of transcription 1(STAT1),STAT3,and STAT5 activated by various cytokines and ribonucleic acid contribute to pSS development,respectively or synergically.These results reveal the potential application of Janus kinase inhibitors for treatment of pSS,which may fundamentally improve the quality of life and prognosis of patients with pSS.

IL-10-producing regulatory B cells restrain the T follicular helper cell response in primary Sjögren’s syndrome

Increased numbers of T follicular helper(Tfh)cells have been implicated in the development of autoimmune diseases including primary Sjögren’s syndrome(pSS),but how the Tfh cell response is regulated during autoimmune pathogenesis remains largely unclear.Here,we first found negative correlations between IL-10^(+)regulatory B(Breg)cell numbers and Tfh cell responses and disease activity in patients with pSS and mice with experimental Sjögren’s syndrome(ESS).Moreover,we detected high expression of IL-10 receptor on Tfh cells and their precursors in both humans and mice.In culture,IL-10 suppressed human and murine Tfh cell differentiation by promoting STAT5 phosphorylation.By using an adoptive transfer approach and two-photon live imaging,we found significantly increased numbers of Tfh cells with enhanced T cell homing into B cell follicles in the draining cervical lymph nodes of RAG-2−/−mice transferred with IL-10-deficient B cells during ESS development compared with those of RAG-2−/−mice transferred with wild-type B cells.In ESS mice,CD19^(+)CD1d^(hi)CD5^(+)Breg cells with decreased IL-10 production exhibited severely impaired suppressive effects on T cell proliferation.Consistently,CD19^(+)CD24^(+)CD38^(hi) Breg cells from pSS patients showed significantly reduced IL-10 production with defective inhibitory function in the suppression of autologous Tfh cell expansion.Furthermore,the adoptive transfer of IL-10-producing Breg cells markedly suppressed the Tfh cell response and ameliorated ESS progression in ESS mice.Together,these findings demonstrate a critical role for IL-10-producing Breg cells in restraining the effector Tfh cell response during pSS development.

Traditional Chinese medicine compound ShengJinRunZaoYangXue granules for treatment of primary Sjogren＇s syndrome： a randomized, double-blind, placebo-controlled clinical trial

Background Traditional Chinese medical treatment of primary Sj（o）gren＇s syndrome has advantages over Western medicine in terms of fewer side effects and improved patient conditions.This study was a multicenter,randomized,doubleblind,placebo-controlled clinical trial of the efficacy and safety of ShengJinRunZaoYangXue granules for the treatment of primary Sj（o）gren＇s syndrome,including the symptoms of dry mouth and dry eye.Methods We undertook a 6-week,double-blind,randomized trial involving 240 patients with primary Sj（o）gren＇s syndrome at five centers in East China.A computer-generated randomization schedule assigned patients at a 2∶1 ratio to receive either ShengJinRunZaoYangXue granules or placebo once daily.Patients and investigators were blinded to treatment allocation.The primary endpoints were the salivary flow rate,Schirmer test results,and sugar test results.Intention-to-treat and per-protocol analyses were performed.Results All 240 patients were randomly allocated to either the treatment group （n=160,ShengJinRunZaoYangXue granules） or placebo group （n=80） and were included in the intention-to-treat analysis.After program violation and loss to follow-up,a total of 199 patients were included in the per-protocol analysis.At six week,intention-to-treat and per-protocol analyses of the left-eye Schirmer I test results showed an improved difference of 1.36 mm/5 min （95% CI：0.03 to 2.69 mm/5 min） and 1.35 mm/5 min （95% CI：0.04 to 2.73 mm/5 min）,respectively,and those of the right-eye Schirmer I test results showed an improved difference of 1.12 mm/5 min （95% CI：0.02 to 2.22 mm/5 min） and 1.12 mm/5 min （95% CI：-0.02 to 2.27 mm/5 min）,respectively.There was no significant difference between the two groups before treatment.After treatment,the between-group and within-group before-and-after paired comparison results were statistically significant （P 〈0.05）.Intention-to-treat and per-protocol analyses showed an improved salivary flow rate by 0.04 ml/15 min （95% CI：-0.49 to 0.58 ml/15 min） and 0.04 ml/15 min （95% CI：-0.52 to 0.60 ml/15 min）,respectively,but the differences were not significant.Intention-to-treat and per-protocol analyses showed that the sugar test results were improved by 1.77 minutes （95% CI：0.11 to 3.44 minutes） and 1.84 minutes （95% CI：0.12 to 3.55 minutes）,respectively,but the differences were not significant.For the secondary endpoint,intention-to-treat and per-protocol analyses showed significant improvement in the integrated evaluation of treated patients with dry eye and dry mouth after six weeks of treatment.The incidence of adverse events was 15.6% in the treatment group and 10.0% in the placebo group.Most （94%） adverse events were mild to moderate in the two groups,and only two cases of serious adverse events occurred in the treatment group; both were caused by autoimmune liver disease.Conclusions Six-week treatment with ShengJinRunZaoYangXue granules for primary Sj（o）gren＇s syndrome in this large-scale study improved the symptoms of dry mouth,dry eyes,and low tear flow rate with minimal adverse events.