Clinical analysis of 8 cases of connective tissue disease complicated with acquired hemophilia A / 中华风湿病学杂志

Objective To analyze the clinical features and treatment of connective tissue disease (CTD) complicated with acquired hemophilia A (AHA).Methods A retrospective analysis of 8 cases of CTD [5 cases of systemic lupus erythematosus (SLE),2 cases of Sj(o)gren's syndrome (SS),1 case of rheumatoid arthritis (RA)] related to clinical manifestations,diagnostic methods,treatment options and outcomes.Results At the onset of AHA,active disease was shown in 7 patients with CTD,and 5 cases had bleeding symptoms in different parts.There were 3 cases of anti-phospholipid syndrome in 5 cases of SLE,2 of which had thrombosis.In 8 patients,the activated partial thromboplastin time (APTF) was prolonged by 1.7 to 3.times,FⅧ∶ C was 9.2％ to 21％ (50％ to 150％),and the factor Ⅷ inhibitor titer was increased by 7.6 to 56 BU/m1 (Bethesda method).Seven patients were treated with sufficient hormones,immunosuppressive agents,human immunoglobulin (IVIG),and blood products.Five patients had clinically improved bleeding tendency and APIT,and one patient was ineffective.Conclusion CTD is easy to combine with AHA.Glucocorticoid combined with immunosuppressive agent can effectively treat CTD-related AHA.For refractory patients,rituximab can be an alternative.

The clinical analysis of 12 patients with immunoglobulin G4 related sialoadenitis and literature review / 中华风湿病学杂志

Objective To explore the clinical characteristics of Immunoglobulin G4 (IgG4) related sialoadenitis,to analyze the difference between the IgG4 related sialoadenitis and Sj(o)gren'syndrome (SS) and to summarize the treatment method and prognosis of the disease,so as to help clinical diagnosis and appropriate treatment.Methods According to inclusion criteria and exclusione criteria,we collected 12 cases of IgG4 related sialoadenitis patients and 78 cases of SS patients from the First Affiliated Hospital of Xinjiang Medical University from 2015-2017.The clinical manifestations,laboratory test,pathological examinations,imaging examinations and the effects of treatment of IgG4 related sialoadenitis were retrospectively anal-yzed.Several aspects of the examination were compared with SS.The count data was analyzed by chi-square test or Fisher exact probality using Statistical program for social sciences (SPSS) 19.0 software.Results Characteristics of IgG4 related sialoadenitis was that one or more pairs of salivary glands and lacimal glands were enlarged with increasing serum IgG4 levels and IgG4+ plasma cell infiltration.Compared with SS,sialoadenitis enlargement (12/12 vs 18/78,x2=24.339,P＜0.01),dry eyes and mouth (9/12 vs 78/78,P＜0.01),serum IgG4 (12/12 vs 0/78,x2=81.554,P＜0.01),antinuclear antibodies (1/11 vs 78/78,x2=71.030,P＜0.01),anti-SSA antibody (0/9 vs 68/78,x2=31.001,P＜0.01),anti-SSB antibody (0/9 vs 36/78,x2=5.311,P=0.021),anti-Ro-52 antibody (0/9 vs 70/78,x2=-35.824,P＜0.01),infiltration of IgG4 positive plasma cell (12/12 vs 0/78,x2=81.554,P＜0.01),therapeutic efficacy of glucocorticoid (6/6 vs 0/34,P＜0.01) was statistically significant.Conclusion IgG4 related sialoadenitis has remarkable characteristics in clinical manifestations,serology,pathology and imaging examinations.Although IgG4 related sialoadenitis and SS have many similarities,we still need to diagnose the disease as early as possible and set up a reasonable treatment plan for patients.

Clinical features, treatment and follow-ups of Sj(o)gren's syndrome-associated monoclonal gammopathy / 中华风湿病学杂志

Objective To investigate the clinical characteristics,immunological features,treatment and follow-ups of Sj(o)gren's syndrome-associated monoclonal gammopathy (SS-MG).Methods A retro-spective,case-control study was conducted for 18 cases diagnosed with SS-MG and 36 age-and sex-matched non-MG-SS patients from Janurary 2010 to Janurary 2017 in Peking University People's Hospital.The clinical and laboratory features,treatment and follow-ups were recorded and compared.Comparisons between groups were made using t test for normally distributed numerical data,Mann-Whitney U test for non-normally distributed numerical data,and Pearson Chi-square,continuity correction or Fisher's exact tests for categorical data.Results SS patients,when complicated with MG,had significantly increased level of TP [(78± 11) g/L,(71±10) g/L,t=-2.382,P=0.021] and erythrocyte sedimentation rate (ESR) [52.5(45.3) mm/1 h,33.0(42.5) mm/1 h,Z=-2.179,P=0.029],higher prevalence of urine NAG positivity [75％(9/12),28％(7/25),x2=7.298,P=0.007],hypoglobulinemia [33％(6/18),3(1/36),x2=7.407,P=0.006] and thrombotic events [17％(3/18),0％(0/36),P=0.033],and less previous exposure to glucocorticoid [22％(4/18),64％(23/36),x2=8.333,P=0.004],compared to the control group.Primary SS patients complicated with MG had significantly higher ESSDAI [26.0(25.0),12.0 (9.0),Z=-2.724,P=0.006] and Clin EULAR Sj(o)gren's syndrome disease activity index (ESSDAI) [24.0(25.0),10.5 (10.0),Z=-2.523,P=0.011].Among the 18 patients,2 were diagnosed with multiple myeloma,1 was diagnosed with non-Hodgkin lymphoma,and the left were diagnosed as MG of undetermined significance (MGUS).Ten patients were followed up,among whom 2 patients with MGUS experienced increased levels of M protein,newly developed genetic abnormalities,and renal involvement.Conclusion SS patients may be complicated with MG.MGUS is the most common form.However,malignant hematologic disorders are revealed as well.In SS patients with high serum TP and ESR,hypoglobulinemia,tubulointerstitial kidney involvement and unexplained thrombotic events,especially in those with high disease activity,so MG should be an alert for further work-ups,monitoring and treatment.

Gender differences in clinical and immunological characteristics and the pathogenic study of primary Sj(o)gren's syndrome / 中华风湿病学杂志

Objective To investigate the clinical and immunological features of primary Sj(o)gren's syndrome (pSS) in both sexs,and to find out the pathophysiology of pSS.Methods Clinical data of 110 pSS cases were analyzed retrospectively,and cytokine levels of interleukin (IL)-2,IL-4,IL-6,IL-10,IL-17A,Tumour necrosis factor (TNF)-α,interferon (IFN)-α were measured (male=20,female=90) in patients and healthy controls (n=30) using enzyme linked immunosorbent assay (ELISA).Results Compared with female patients,no significant difference was found in male patientsin symptoms of dry mouth and dry eye (90.0％ vs 98.9％,x2=4.874,P＞0.05);the frequency of parotid gland enlargement and lymphadenectasis were higher in male (40.0％ vs 5.6％,x2=18.629,P＜0.01;25.0％ vs 6.7％,x3=6.111,P＜0.05);and the level of immunoglobu lin (Ig)A and C4 [2.2(1.5,3.0) g/L vs 3.3(2.5,5.0) g/L,Z=-3.119,P＜0.01;(0.15±0.05) g/L vs (0.19±0.08) g/L,t=-2.659,P＜0.05] were lower in male,as well as the incidence of positive anti SSA/SSB antibodies (55.0％ vs 78.8％,x2=4.921,P＜0.05).Cytokine levels of IL-2,IL-6,TNF-α (t=-3.783,-6.193,-2.065,P＜0.05) were higher in pSS than HC.Compared with female patients,cytokine levels of IL-10,IFN-γ (t=-1.075,6.286,P＜0.05) were higher in male,however,the levels of IL-2,TNF-o (t=-3.472,-5.867,P＜0.01) were lower in male.Conclusion There are differences in the cytokine levels secreted from Thl and Th2 cell between male and female patients of pSS,which may relate to the clinical and immunological characteristics and can help to reveal the pathophysiology of pSS.

Central nervous system involvement in primary Sj(o)gren's syndrome: a study of 38 patients / 中华风湿病学杂志

Objective To analyze the clinical profile of primary Sj(o)gren's syndrome (pSS) patientswith central nervous system (CNS) involvement.Methods Thirty-eight pSS-CNS patients at Nanjing Drum Tower Hospital between 2012 and 2016 were enrolled.These patients were divided into high activity group and moderate activity group,according to European League against Rheumatism Sj(o)gren's syndrome Disease Activity Index (ESSDAI).The imaging characteristics,clinical features,laboratory examinations and treatment of 38 cases were retrospectively analyzed.Quantitative differences were analyzed by the student's t-test and qualitative data were analyzed with chi-square or Fisher's exact test.Results The prevalence of central nervous system involvement in pSS patients was 2.93％(38/1 296),while 32％(12/38) as the initial symptom of pSS.Recurrence rate was 39％(15/38).Limb weakness,speech difficulty,sensory disorders,blurred visionwere the most frequent symptoms in pSS-CNS.Multiple lesions in Magnetic resonance imaging (MRI) examination and cerebrospinal fluid abnormality were seen in 94％ (15/16) pSS-CNS patients,among which intra-thecal IgG level increased in 50％ (8/16).In addition,the frequencies of lung involvement,immune associated thrombocytopenia,high-titer antinuclear antibody (ANA) were significantly higher in high activity group of pSS-CNS than those of moderate activity group.The value of above items was 4.7,5.0 and 5.3,respectively,and all the differences were significant (P＜0.05).After high-dose corticosteroids and immunosuppressive therapy,61％ (23/38) patient improved,37％(14/38) were unresponsive to treatment,and 3％(1/38) died because of acute massive cerebral infarction.For those unresponsive patients,mesenchymal stem cell transplantation or immune adsorption treatment might be effective.Conclusion The clinical manifestations of central nervous system are diverse,may be the initial presentations in some pSS patients,with low morbidity and high recurrence rate.Image and lumbar puncture are important for diagnosis.Pulmonary involvement,immune thrombocyto-penia,and high-titer ANA are frequently associated with the activity of pSS-CNS.Most patients have good response to the treatment regimens of high-dose corticosteroids and immunosuppressive therapy,mesenchymal stem cell transplantation or immuno-sorption therapy may be considered in those unresponsive cases.

Mesenchymal stem cells inhibit the activation and proliferation of CD4+ T cells in Sj(o)gren syndrome by promoting prostaglandin E2, hepatocyte growth factor and indoleamine 2, 3-dioxygenase secretion / 中华风湿病学杂志

Objective To investigate the suppressive effect of prostaglandin E2 (PGE2),hepatocyte growth factor (HGF) and indoleamine 2,3-dioxygenase (IDO) whose secretion was promoted by human umbilical cord mesenchymal stem cells(MSCs) on the activated peripheral blood CD4+ T cells in primary Sj(o)gren syndrome (pSS) in vitro.Methods Primary cultured umbilical cord MSCs were identified by flow cytometry,and peripheral blood CD4+ T cells were sorted in pSS patients.CD4+ T cells were cultured with CD3,CD28 antibody for 72 h to be the activated(control group);the activated CD4+ T cells were co-cultured with MSCs for 72 h(MSCs group) or MSCs were pre-stimulated with interferon-γ (IFN-γ),then the activated CD4+ T cells were co-cultured with pre-stimulated MSCs for 72 h (pre-stimulated group).The suspension of CD4+ T cells were collected and counted.PGE2,HGF and IDO in the supernatants were detected by ELISA.Mean in groups were compared using ANOVA,and multiple comparisons were used with LSD method.Results The concentrations of PGE2 in the supernataut of the control group,MSCs group and pre-stimulated group were (111 ±4) pg/ml,(2 814±6) pg/ml and (2 716±8) pg/ml (F=167 292.12,P＜0.01) respectively.The concentrations of HGF in the above groups were (597±9) pg/ml,(383±9) pg/ml and (727±12) pg/ml(F=878.61,P＜0.01) respectively.The concentrations of IDO in the above groups were (143±4) pg/ml,(835±5) pg/ml and (588±3) pg/ml (F=21 104.41,P＜0.01) respectively.Compared with the control group,levels of PGE2 significantly increased in the MSCs group and the pre-stimulated group that CD4+ T cells were co-cultured with MSCs (t=509.88,P＜0.01 and t=491.48,P＜0.01),and levels of IDO also significantly increased (t=202.69,P＜0.01 and t=130.39,P＜0.01),while the activation and proliferation of CD4+T cells were inhibited (t=-16.20,P＜0.01 and t=-31.48,P＜0.01).Compared with MSCs group,levels of PGE2 and IDO significantly decreased in pre-stimulated group (t=-18.40,P＜0.01 and t=-72.30,P＜0.01),and levels of HGF significantly increased in pre-stimulated group(t=41.51,P＜0.01),while the activation and proliferation of CD4+ T cells were further inhibited (t=-15.28,P＜0.01).Conclusion MSCs can inhibit the activation and proliferation of CD4+ T cells in pSS in vitro.The suppressive effect of MSCs may be achieved by promoting secretion of cytokines such as PGE2,HGF and IDO.HGF plays a more important role in the suppressive effect of MSCs pre-stimulated with IFN-γ.Too much PGE2 or IDO propably results in negative feedback regulation of MSCs.

Research progress in renal injury relevant to primary Sj(o)gren's syndrome / 中南大学学报(医学版)

Primary Sj(o)gren's syndrome (pSS) is a chronic autoimmune disease characterized by lymphoplasmacytic infiltration of the exocrine glands that results in multiple organs and systems damage.Renal injury affects 0.3％-27.0％ patients,The most frequent form of nephropathy in pSS is tubulointerstitial nephritis.The main clinical manifestation is renal tubular acidosis.The renal prognosis in patients with pSS is usually favorable,but renal failure may occur.At present,it still lacks of strict consensus or guideline for the treatment.

Treatment progress of primary sj(o)gren's syndrome / 中国免疫学杂志

Primary Sj(o)gren' s Syndrome (pSS)is a chronic autoimmune disease with complex and diverse clinical manifestations.It is characterized by lymphocyte infiltration of exocrine glands such as the salivary gland and lacrimal gland leading to insufficient secretion of the gland,manifested as dry mouth and dry eyes.The disease in addition to exocrine glands cause damage,but also involving organs outside the gland,resulting in systemic systemic injury.The pathogenesis of pSS is not clear yet.Currently,symptomatic treatment is the mainstay of pSS,and the exact treatment is lacking.However,there are some new treatments in recent years.

Changes of serum Krebs von den Lungen-6 levels in interstitial lung disease associated with dermatomyositis and secondary Sj(o)gren's syndrome: a case report / 北京大学学报(医学版)

Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung.The underlying pathogene sis of ILDs is complex and associated with multiple rheumatologic conditions,such as systemic sclerosis,rheumatoid arthritis,pollymyositis and dermatomyositis,Sjt(o)gren's syndrome,and systemic lupus erythematosus.As the disease progresses,excessive pulmonary fibrosis impairs alveolar gas exchange and damages pulmonary function.The common methods to diagnose ILDs,such as clinical manifestations,pulmonary function test,and radiological examinations are not specific for ILDs and not able to diagnose ILDs at the early stage due to their low sensitivity.So,the easy way is important to diagnose ILDs.One important biomarker for ILDs is the high-molecular-weight glycoprotein,Krebs von den Lungen-6 (KL-6).KL-6 encoded by the MUC1 gene is a mucin-like glycoprotein with high molecular weight and expressed predominantly on the cell surface of type Ⅱ alveolar epithelial cells,and is detectable in the serum of patients with ILDs.We here report a case of ILDs associated with dermatomyositis and secondary Sj(o)gren's syndrome.A 60-year-old woman was admitted to our hospital with the chief complaints of debilitation,dry mouth,dyspnea and astasia.ILDs associated with dermatomyositis and secondary Sj(o)gren's syndrome was diagnosed clinically when the following criteria were satisfied:(1) development of dyspnea within 2 months of presentation,(2) pulmonary dispersion dysfunction,(3) bilateral infiltrative shadows on chest high resolution computed tomography (HRCT).She was treated with prednisone 50 mg/d prior to admission,but the result of therapy was not good.In our hospital she was treated with intravenous methylprednisolone and cyclophosphamide and oral hydroxychloroquine sulfate.Subsequently,her serum KL-6 levels gradually decreased after treatment,pulmonary diffuse function improved,and the improvement in the clinical manifestation and HRCT findings were observed.Nevertheless,the combination treatment of glucocorticoid and cyclophosphamide had contributed to the favourable outcomes.In conclusion,detection of serum KL-6 levels in ILDs associated with connective tissue diseases may be beneficial to making a definitive diagnosis,predicting the prognosis and monitoring the disease activity,which would be of great help in clinical practice.However,a well-designed clinical study with more patients and a longer follow-up period are required to arrive at a more conclusive judgment on the role of serum KL-6 in patients with ILDs.

Clinical analysis of the neurological involvement in primary Sj(o)gren's syndrome / 中华风湿病学杂志

Objective To analyze the clinical and laboratory manifestations of primary Sj(o)gren's syndrom (pSS) with neurological involvement.Methods One hundred and forty eight patients fulfilling the 2002 American-European pSS classification criteria were retrospectively analyzed.Neurological manifestations were diagnosed based on the clinical,biological,electrophysiological,and imaging findings.Biographical,clinical,and laboratory data were compared between patients with and without neurological manifestations.Statistical methods used were Mann-Whitney U test,Chi-square test and Fisher exact probability.Results The prevalence of neurological involvement in pSS was 20.3％ (30/148),and the incidence of peripheral neuropathy,the central neuropathy and combination of the central neuropathy with peripheral neuropathy were 10.1％(15/148),9.5％(14/148) and 0.7％(1/148),respectively.The clinical spectrum of peripheral neuropathies encountered in Sj(o)gren's syndrome (SS) patients varied,with the pure sensory neuropathies being the most common,followed by sensorimotor neurophathies.Motor neuron disease was the most common type of central neurophathies.Compared with those without neurological manifestations,the duration of peripheral nerve system/central nerve system (PNS/CNS)-pSS patients was relatively short [(55±76) months vs (100±108) months,Z=-2.682,P＜0.05],and the antinuclear antibody (ANA) titer and RF titer were lower [(234±248) vs (377±339),Z=-2.008,P＜0.05;(126±279) U/ml vs (359±1 445) U/ml,Z=-2.243,P＜0.05].In PNS/CNS-pSS patients,the most common clinical manifestations included numbness (50％),pain (23％),and muscle weakness (63％).Conclusion The prevalence of neurological involvement in pSS is high.The duration is relatively short and the disease activity is high,but the disease features are atypical and may be neglected by rheumatologists.

LC-MS based measurement of androgens and its clinical significance in diagnosis of Sj(o)gren's syndrome / 中国基层医药

Objective To evaluate the clinical value of 6 androgens in the serum of Sj?gren's syndrome (SS) measured by liquid chromatography tandem mass spectrometry (LC-MS).Methods 32 SS patients (SS group) and 25 healthy people (healthy group) were included in this study.6 androgens in the serum were analyzed by LC-MS after prepared.PCA,PLS-DA models and t-test were used to class differentiation of androgens between two groups.Results The results of PLS-DA showed that SS group and healthy group could be well classed by 6 androgens.The levels of testerone (T),dihydrotestosterone (DHT),dehydroepiandrosterone (DHEA),androsterone and DHEAS in SS group were significantly lower than those in healthy group (t=8.536,2.438,3.172,4.158,4.489,all P<0.05).The samples before or after menopause could be distinguished between the two groups by PLS-DA.Conclusion The significant difference of androgens was discovered between SS patients and healthy people via the measurement of 6 androgens in serum.It may arise a new idea for diagnosis and treatment of SS.

A multi-center clinical study for ANA specific autoantibodies detection by chemiluminescent immunoassay / 中华检验医学杂志

Objective To evaluate the clinical performance of chemiluminescent immunoassay (CLIA) on anti-nuclear antibody(ANA) specific autoantibodies testing.Methods A multi-center clinical study A total of 811 Sera samples were collected from 6 collaborating hospitals during the period of April to July 2016, and tested with CLIA and line immunoassay (LIA) in parallel for autoantibodies to ribonucleoprotein(RNP), smith antigen(Sm), SSA/Ro60,SSB/La, centromere protein B(CENPB), double-stranded DNA(dsDNA), nucleosome(Nuc), and ribosome P protein(Rib-P).The positive rate,specificity and qualitative coincidence rate for each antibody between CLIA and LIA methods were analyzed.All discrepant samples for systemic lupus erythematosus (SLE) highly specific autoantibodies (including anti-Sm, dsDNA, Nuc and Rib-P) were retested by enzyme linked immunosorbent assay (ELISA) and further analyzed with SLE disease cohort using McNemar test.Results The positive rate and specificity of CLIA and LIA for antibodies to ANA specific antigens were comparable.Excellent qualitative coincidence were found between CLIA and LIA for the detection of anti-RNP, SSA/Ro60, SSB/La and CENPB (Kappa>0.75), while the coincidence rate foranti-Sm, dsDNA, Nuc and Rib-P detection were moderate (0.4

Clinical features of primary Sj(o)gren's syndrome associated lung involvement in patients with extra-glandular manifestations at disease onset / 中华风湿病学杂志

Objective To investigate the common initial clinical presentations of primary Sj(o)gren's syndrome (pSS) with pulmonary complications,and to explore the differences between patients with extraglandular manifestations at disease onset (EGM) and those with glandular manifestations at disease onset (GM).Methods A total of 1 341 hospitalized SS patients from 2003 to 2012 were retrospectively reviewed.Of them,102 hospitalized patients with pSS'associated lung disease were analyzed and included.Case control study was performed to explore the differences between the EGM group and the GM group.Results Fifty-one percent of patients were presented with EGM at onset,with significantly shorter disease duration [36 (12,156) m vs 102 (48,159) m,x2=-2.41,P=0.016].Although the mean diagnose time was similiar,only 4％ of the EGM group could be confirmed the pSS diagnose at onset,which was significantly less frequently than that of the GM group (34％,22=15.29,P＜0.01).Case control study revealed that hyperglobulinemia,elevated RF titers and anti-SSA and/or anti-SSB test positive were less predominant in the EGM group [IgG 16(12,21) g/L vs 21 (15,28) g/L,x2=-2.15,P=0.032;22 (20,171) U/ml vs 104 (20,238) U/ml,x2=-l.98,P=0.048;33％ vs 72％,x2=15.78,P＜0.01].The predicted value of TLC and FVC were lower [(87±23)％ vs (97±20)％,x2=-1.96,P=0.050;(8±28)％ vs (100±27)％,x2=-1.70,P=0.089] and HRCT score was higher in EMG group [12(88,15) vs 8(5,13),x2=-1.82,P=0.070].Conclusion EMG at onset is the common initial manifestation of pSS'associated lung involvement.Pulmonary complication is more progressively and severe than those with MG at onset.Anti'SSA positive,elevated RF titer and hyperglobulinemia are not predominant for patients with EMG at onset.

Clinical Characteristics of 65 Male Patients with Sj(o)gren's Syndrome / 医学研究杂志

Objective To analyze the different clinical features and system lesions of female and male primary Sj(o)gren's syndrome (pSS) patients and to attract more attention to male pSS patients' pathogenic features.Methods Clinical information of pSS patients was gathered and physicochemical tests were conducted.The clinical features of female and male patients were summarized and analyzed.Results 935 pSS cases were collected,among which 65 cases were male.The male-female ratio was 0.7∶ 10.The man's median duration of diagnosis was 10 months,with a median duration of 36 months,compared with women's time (P ＜ 0.05).There were significant statistical differences between both the dry mouth and dry eyes occurrence rate of female and male patients (P ＜ 0.05).In ophthalmic Schirmer tests,440 female patients and 8 male presented abnormal results (P ＜ 0.05).For labial gland biopsy,the positive rate of male patients was much higher than that of the female (P ＜ 0.05).The incidence of lymphadenectasis of male patients was 16.9％,which was higher than that of female patients (5.2％),presenting statistical significance (P ＜ 0.05).As regards pSS system lesions,54.48％ of the female presenting presented system lesions,while this rate for male patients was only 36.92％;the rate of multiple system lesions for female and male patients was 10.8％ and 3％ (P ＜ 0.05).The incidence of lymphadenectasis of male patients was higher than that of female patients (P ＜ 0.05).As regards pSS system lesions,the incidence of multiple system involvement was low(P ＜ 0.05).Conclusion The incidence of male pSS is significantly lower than that of female.Dry mouth dryness is lower than that of female,and there is no difference in digestive,respiratory,urinary and nervous system involvement.

Immunophenotypes and clinical features of lymph ocytes in labial gland of patients with primary Sj(o)gren's syndrome / 中华风湿病学杂志

Objective To investigate the consistency of the lymphocyte immunophenotype between labial gland and peripheral blood of patients with primary Sj(o)gren's syndrome (pSS).Methods Seveny-one pSS patients (referred as pSS group) from rheumatology department and 35 subjects patients with maxillofacial trauma (referred as control group) from department of head and neck surgery of general hospital at tianjin medical university (Tianjin,China) during August 2013 to April 2016 were included into this study.Based on the ratio of CD20 to CD3 in labial gland from pSS patients,they were divided into CD20 high proportion group and CD20 low proportion group.Lymphocyte immunophenotypes in labial glands,course of disease,erythrocyte sedimentation rate (ESR),C-reactive protein (CRP) level,immuno-globulin (Ig) and complement levels were compared among groups.Results ① The levels of serum IgG,IgA,IgM and CRP,and ESR were higher,but C4 level was lower in pSS patients than in the control group [IgG:(22 990±8 060) mg/L vs (1 1560±1 290)mg/L,t=l 1.645,P＜0.01;IgA:(3 710±1 400) mg/L vs (2 390±800) mg/L,t=6.138,P＜0.01;IgM:(1 580±1 300)mg/L vs (920±390) mg/L,t=3.893,P＜0.01;ESR:(37±14) mm/1 h vs (14±4) mm/1 h,t=12.723,P＜0.01;CRP:(5.9±8.7) mg/L vs (2.5±1.2) mg/L,t=3.199,P＜0.01;C4:(180±60) mg/L vs (250±40) mg/L,t=-6.850,P＜0.01].② The levels of IgG,IgA,IgM and C3c in labial gland were higher (IgG:Z=-6.264,P＜0.01;IgA:Z=-1.997,P＜0.05;IgM:Z=-5.459,P＜0.01;C3c:Z=-8.533,P＜0.01),but Clq was lower in pSS group than in control group (Z=-4.363,P＜0.01).③ CD20 was detected in labial gland samples of all pSS patients,in which CD3 was positive in 66 patients,and negative in 5.④ Serum IgG level,ESR were higher in CD20 high proportion group than in low proportion group [IgG:(24 970±7 510) mg/L vs (18 860±7 740) mg/L,t=3.176,P＜0.01;ESR:(40±13) mn/1 h vs (32±15) mm/1 h,t=2.148,P＜0.05].⑤ The levels of IgG and Clq in labial gland were higher in CD20 high proportion group than in low proportion group [IgG:Z=-5.387,P＜0.01;C1q:Z=-4.724,P＜0.01].Conclusion pSS patients have a higher proportion of CD20 in infiltrating lymphocytes of the labial gland,accompanied with the changes of immunoglobulins and complements in both labia gland and peripheral blood.

A Sj(o)gren's syndrome patient with prominent aortic valve involvement: a case report / 北京大学学报(医学版)

Sj(o)gren's syndrome is a systemic autoimmune disease which is characterized by xerosis,and multiple organs can be affected,causing interstitial lung disease,renal tubular acidosis,blood system involvement,peripheral neuropathy,and liver damage,but cardiac involvement is rare.Here we report a case of Sj(o)gren's syndrome with prominent aortic valve involvement.A 66-year-old woman was admitted for exertional dyspnea,and the ultrasonic cardiogram showed severe aortic stenosis with moderate regurgitation.Preoperative examination for valve replacement found that the patient had elevated erythrocyte sedimentation rate and positive rheumatoid factor,so she was referred to the rheumatology outpatient department for further examination and treatment.Further questions about medical history found that the patient had dry eyes and dry mouth for more than ten years,and had obvious caries.Further laboratory examination showed elevated serum immunoglobulin levels and positive anti-nuclear antibody.The findings of ophthalmologic examination and labial gland biopsy also supported the diagnosis of Sj(o)gren's syndrome.After treatment of glucocorticoids and hydroxychloroquine for ten months,her dyspnea symptoms were obviously improved in the patient,and the rheumatoid factor had become negative while her erythrocyte sedimentation rate normal.Repeated ultrasonic cardiogram examination showed that her aortic stenosis was also improved.The patient has been followed up for four years,and her condition kept stable.Cardiac involvement in Sj(o)gren's syndrome can affect all parts of the heart,but valve involvement is relatively rare.The specific relationship between cardiac involvement and Sj(o)gren's syndrome and the mechanisms behind these associations both need further research.

Diagnostic value of salivary gland ultrasonography scoring systems in Sj(o)gren's syndrome / 中国医学影像技术

Objective To explore the value of salivary glands ultrasonography in diagnosis of Sj(o)gren's syndrome (SS).Methods Ninety-two patients with symptoms of xerophthalmia or xerostomia were enrolled,and 42 of them were divided to the SS group and the others to non-SS group.The bilateral parotid and submandibular gland of all patients were examined with ultrasonography,then the ultrasonographic features of bilateral salivary glands were obtained.The imaging features of salivary glands were evaluated by a semi-quantitative scoring system.The differences of ultrasonography scores between SS group and non-SS group were compared.The value of semi-quantitative scoring system in diagnosis of SS was analyzed.Results Salivary gland ultrasonic manifestations of 38 patients (38/50,76.00％) in non-SS group were normal,whose ultrasonographic scores were 0.Whereas the ultrasound of 32 patients (32/42,76.19％) were abnormalities in SS group,whose ultrasonographic scores were ≥1.Ultrasonographic scores in SS group were higher than that of non-SS group (P＜0.001).The area under the ROC curve of ultrasound score in diagnosis of SS was 0.805 (P＜0.001,95％ confidence interval was [0.711,0.899]).When the cutoff value of the scores was 2,the sensitivity and specificity were 59.5 ％,and 92.0％.Conclusion The ultrasonographic scoring of salivary glands can provide a semi-quantitative index for inhomogeneity of the salivary glands,which has significant value in the diagnosis of SS.

Salivary gland scintigraphy in diagnosis of Sj(o)gren's syndrome / 中国医学影像技术

Objective To assess the value of salivary gland scintigraphy in diagnosis of Sj(o)gren's syndrome (SS).Methods A total of 44 patients with clinically suspicious SS were included.The data of salivary gland scintigraphy were retrospectively analyzed and the time-radioactivity curve (TAC) was obtained by outlining ROI in bilateral parotid glands and submaxillary glands.Uptake index (UI) and excretion fraction (EF) were defined.Both UI and EF were compared with the visual assessment and final diagnosis respectively.Results UI and EF of bilateral parotid glands and submaxillary glands in SS patients were significantly lower than those in non-SS patients (all P＜0.05).The impaired salivary gland function was classified as 0-3 grades by visual assessment.The UI of bilateral parotid glands and submaxillary glands were negatively correlated with the qualitative classification.While there were no significant correlations between EF and qualitative classification (all P＞0.05),except for that of right submaxillary gland (r=-0.312,P=0.039).The comprehensive diagnostic efficacy of UI on SS patients was higher than those of visual assessment,but their area under curves of ROC were not significantly different (all P＞0.05).Conclusion UI and EF can effectively evaluate salivary gland function and serve as objective tools to distinguish patients with SS.

Diagnostic value of a modified dynamic salivary gland scintigraphy for Sj(o)gren's syndrome / 中华核医学与分子影像杂志

Objective To establish a modified dynamic 99Tcm-pertechnetate salivary gland scintigraphy(SGS) method,and to evaluate the value in the diagnosis of Sj(o)gren's syndrome(SS) by comparing SGS with labial gland biopsy (LGB).Methods A total of 204 patients (21 males,183 females,age range 20-85 years) with suspected SS who underwent the modified dynamic SGS and LGB were enrolled in this prospective study.Uptake ratio (UR) and excretion fraction (EF) of the left parotid gland (LPG),the right parotid gland (RPG),the left submandibular gland (LSG) and the right submandibular gland (RSG)were calculated.Two-sample t test was used for data analysis.The sensitivity,specificity,accuracy of the modified dynamic SGS and LGB were calculated,and x2 test was used for data analysis.Results SS was confirmed in 113 patients,including 79 patients with primary SS and 34 patients with secondary SS.SS was excluded in 88 patients.The UR and EF of the SS group (LPG:1.95±1.04 and (52.2±19.5)％,RPG:1.96±1.06 and (55.0±21.1)％,LSG:2.65±1.12 and (25.9±14.1)％,RSG:2.72±1.30 and (29.7± 14.7) ％) were significantly lower than those of the non-SS group (LPG:3.08± 1.10 and (65.9± 12.7) ％,RPG:3.26±1.16 and (66.4±12.6)％,LSG:3.71±1.31 and (43.2±12.3)％,RSG:3.74±1.39 and (46.6± 11.5) ％;t=4.40-9.00,all P＜0.05).The sensitivity,specificity,accuracy of the modified dynamic SGS were 99.1％ (112/113),72.7％ (64/88),87.6％ (176/201),respectively,while those of LGB were 83.2％ (94/113),96.6％ (85/88),89.1％ (179/201),respectively.The sensitivity and specificity of SGS method were significantly different from those of LGB (x2 =15.9,17.5,both P＜0.05).Conclusions The modified dynamic SGS can reduce the acquisition time and has a high sensitivity for SS.When combined with LGB,it will improve the diagnostic accuracy for SS.

Clinicopathologic characteristics and prognosis of Sj(o)gren's syndrome complicated with renal involvement / 中华风湿病学杂志

Objective To analyze the clinical manifestations,immunological characteristics,pathological changes and prognosis in primary Sj(o)gren's syndrome complicated with renal involvement.Methods Three hundred and eighty-seven patients with pSS were enrolled in this retrospective study.Among these patients,198 patients were complicated with renal involvement and 189 patients without renal involvement.The data of the two groups were analyzed for clinical manifestations,blood tests,urine tests and immunological characteristics by independent sample t test,x2 test,Fisher exact probability and Logistic regression model respectively.Seventy-two patients in the group with renal involvement had kidney biopsies.Results The average of these 387 patients (female/male 345/42 cases) were (55.3±13.2) years old.The average age of 198 patients with renal involvement (female/male 168/30 cases) was (55.3±13.2) years old.The serum RF and IgG of the group with renal volvement was significantly higher than the patients without renal involvement.In the 198 patients with renal involvement;102 patients (51.5％) developed type Ⅰ renal tubular acidosis (RTA Ⅰ).Among these RTA Ⅰ patients,54 patients presented hypokalemia;12 patients developed hypokalemic plegia,30 patients with urolithiasis,6 patients with osteoporosis;69 patients presented with overt renal glomerulus impairment,36 cases had nephrotic syndrome (NS),and 33 cases had chronic glomerulonephritis;In 81 patients with renal failure,including 27 were stage 1 CKD,18 were stage 2 CKD,9 were stage 3 CKD,15 were stage 4 CKD,12 were stage 5 CKD.Among these patients with renal biopsie,light microscopy showed chronic interstitial nephritis (IN,69/72),mesangial proliferative glomerulonephritis (36/72),hyperplastic and sclerosing glomerulonephritis (9/72),partly sclerosing glomerulonephritis (9/72) and membranous nephropathy (6/72).Immunofluorescent examination revealed:IgG deposition in 21 patients (29.1％),IgA in 21(29.1％),IgM in 33(45.8％),C3 in 12(16.6％),C4 in 18(25％) and C1q in 15(20.8％).Sixty-six cases with renal biopsies were followed for (8-30)months,except the patient died of cerebral bemorrhage,all the other patients survived,and renal functions were steady or improved.Conclusion ① The pSS patients with renal involvement mainly shows interstitial nephritis.However,the occurrence of glomerulonephritis is not rare.② Rheumatoid factor (RF) or IgG is significantly associated with renal involvement in patients with pSS.③ When renal involvement is presents,renal biopsies is a necessary for patients with pSS.