Prognostic Study Of Primary Sjögren's Syndrom

Part Ⅰ:Hyperglobulinemia predicts increased risk of mortality in primary Sj(?)gren’s syndrome:based on a Chinese multicenter registryObjectives:To investigate whether pSS patients with hyperglobulinemia have an increased risk of all-cause mortality.Methods:Patients who registered in Chinese Rheumatism Data Center from May 2016 to July 2021,and met the 2002 AECG criteria or 2016 ACR/EULAR classification criteria for SS were included.Hyperglobulinemia was defined as any elevated serum levels of IgG,IgA,or IgM.The primary outcome was all-cause death.Data for demographic and clinical characteristics,laboratory findings,disease activity index,damage scores and treatments were analyzed.Results:A total of 9,527 pSS patients were included in the study,of whom 4,236(44.5%)had at least one kind of elevated immunoglobulin level among IgG,IgA,and IgM.The risk of death significantly increased in patients with hyperglobulinemia(crude HR 2.60,95%CI 1.91-3.55;adjusted HR 1.90,95%CI 1.20-3.01).Risk of death was positively correlated with IgG level(P trend<0.001).The 5-,10-,and 15-year survival rates of patients with hyperglobulinemia were 96.9%,92.3%,and 87.9%,respectively,and significantly lower than the corresponding rates of 98.8%,97.9%,and 96.4%in patients without hyperglobulinemia.Conclusions:Hyperglobulinemia is an independent risk factor for increased all-cause mortality in pSS patients.Risk of death is positively correlated with IgG level.Part Ⅱ:Predictive value of bone marrow megakaryocyte count for immunotherapeutic response in primary Sj(?)gren’s syndrome patients with severe immune thrombocytopenia:a single-center case-control study in ChinaObjectives:To investigate potential predictors of treatment response in primary Sj(?)gren’s syndrome(pSS)patients with severe immune thrombocytopenia(ITP),with a focus on bone marrow megakaryocyte(MK)count.Methods:This case-control study included patients with pSS and severe ITP who were admitted to Peking Union Medical College Hospital from Janaury 1st 2013 to February 28th 2022 and met the 2002 AECG or 2016 ACR/EULAR criteria for SS.Patients who overlap other connective tissue diseases,or thrombocytopenia that could be explained by other causes were excluded.Severe ITP was defined as platelet count<20×109/L.Treatment response was evaluated at 3 months after treatment.Subgroup analysis was conducted among patients who received rituximab.Results:Sixty-eight eligible patients were included:34(50%)achieved complete remission(CR),18(26%)partial remission(PR)and 16(24%)were non-responders(NRs).Fewer infections were found in the CR group(24%)than in the PR(50%)and NR(56%)groups(P=0.04).The MK count(CR 32 vs PR 36 vs NR 4 per slide,P<0.001)in the NR group was significantly lower than in the other groups.MK count>6.5 per slide predicted good treatment response,with a sensitivity of 85.7%and a specificity of 88.1%.Logistic regression indicated that patients with more MKs were more likely to respond to immunotherapy(crude OR 1.45,95%CI 1.2-2.0;adjusted OR 1.68,95%CI 1.2-2.7).Among 16 patients who received rituximab,patients with CR or PR had significantly more MK than patients with NR,and there was no significant difference in subgroup analysis of peripheral lymphocytes among the three groups.Conclusions:MK count could predicte response to immunosuppressive treatment in pSS patients with severe ITP.The bone marrow aspiration are recommended before initiation of treatment in pSS patients with severe ITP.Clinicians should pay attention to infections during clinical practice.Part Ⅲ:Primary Sj(?)gren’s syndrome is associated with increased risk of malignancies besides lymphoma:a systematic review and meta-analysisObjective:The aim of this study is to investigate the association between pSS and the risk of malignancy,with a focus on hematological malignancies besides lymphoma and solid tumors through a systematic review and meta-analysis.Method:We searched PubMed and EMBASE by March 21 st 2021.Inclusion criteria were as follows:(1)pSS was the exposure of interest;(2)newly developed malignancies were the outcome of interest;(3)standardized incidence ratio or relative risk with 95%confidence interval or essential data to calculate them were reported.(4)Study design was cohort study or registry-based study.Patient with other connective diseases were excluded.Quality assessment was conducted according to Newcastle-Ottawa Scale for cohort study.Random or fixed effect models were used to calculate the pooled SIR according to heterogeneity measured by I2.Results:A total of 1003 articles were found by a comprehensive search in PubMed and EMBASE.Twenty-eight articles were eligible.Four of them were from the same database,and the one with longest observational span was chosen.Therefore,twenty-five articles were included for final analysis,which involved more than 47,607 pSS patients with the follow-up of more than 452,468 person-year.We found that pSS was significantly associated with increased risks of overall malignancy(SIR 2.17,95%1.57-3.00),hematological malignancy(SIR 11.55,95%CI 4.32-30.90)including NHL(SIR 13.71,95%CI 8.83-21.29),Hodgkin lymphoma(SIR 8.84,95%CI 5.00-15.61),multiple myeloma(SIR 8.27,95%CI 3.08-22.24),leukemia(SIR 2.56,95%CI 1.78-3.69),and solid tumors(SIR 1.39,95%CI 0.90-2.13)including lung cancer(SIR 1.55,95%CI 1.29-1.85),thyroid cancer(SIR 2.05,95%CI 1.20-3.48),non-melanoma skin cancer(SIR 1.71,95%CI 1.08-2.72),kidney/urinary tract cancer(SIR 1.36,95%CI 1.02;1.81),liver cancer(SIR 1.70,95%CI 1.13-2.57)and prostate cancer(SIR 1.50,95%CI 1.02-2.22).Conclusion:This meta-analysis showed that pSS patients had increased risk of overall cancer,which not only contributed by NHL,but also by other hematological malignancies and solid tumors.