Ziwan-Taoren herb pair can exert an therapeutical effect in primary Sjogren’s syndrome through inhibiting the TLR/NF-κB pathway

Background:Ziwan and Taoren(ZT)is a classic medicine pair in the formula of Mai Dong Di Shao Decoction,has been used to treat primary Sjogren’s syndrome(pSS)for more than 20 years.But its action mechanism is still unknown.This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS.Methods:Firstly,the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis.Secondly,the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques.Finally,efficacy and mechanism were conducted through in vivo experiments,such as water intake,spleen index,hematoxylin-eosin staining pathological changes,ELISA,Western Blot analysis,and immunofluorescence staining.Results:Nine active compounds were extracted from network pharmacology,including quercitrin,luteolin,kaempferol,β-sitosterol,isorhamnetin,galangin,hederagenin,diosmetin and gibberellin 7.Seven disease targets were identified:RELA,TP53,AKT1,interleukin(IL)6,MAPK1,ESR1,IL10;with RELA being the most core target.KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process.preliminary results of molecular docking showed that ZT’s active compounds bind well to the RELA(p65)receptor.In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice.The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased,while levels of inflammatory factors such as tumor necrosis factor-α,IL-6,and IL-1βalong with protein expressions including toll-like receptor4,p-p65 and p-IKKα/βin NF-κB pathway were reduced.Conclusions:The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS,potentially attributed to its capacity for suppressing the TLR/NF-κB inflammatory signaling pathway.

Persistent Xerophthalmia in a Patient with Rheumatological Disease and Priiviary Sjogren’s Syndrome: Case Report from Northern Brazil

This case study aims to contribute to the literature in order to highlight the importance of this collaboration between medical specialties. A female patient R.N.N. F, age 66, from the city of Manaus, with a previous diagnosis of Sjogren’s syndrome in regular follow-up by the Rheumatology team at the Araujo Lima outpatient clinic and referred to the Ophthalmology sector for complementary evaluation related to visual discomfort. The fundoscopy performed in the patient was within normal limits, but the symptoms experienced by her proved to be an important clinical finding, which has ratified the need for regular and multidisciplinary follow-up. This report unequivocally demonstrates that even in the face of tests considered within the expected limits for a given population, the clinical presentation can be specific and particular for each analyzed individual. Early screening exams should contemplate the patient in a holistic and individualized way whenever possible.

Visual resolution under photopic and mesopic conditions in patients with Sjogren's syndrome

AIM:To focus on different visual resolution tasks under photopic and mesopic conditions in Sjogren’s syndrome patients compared to age-matched healthy controls.METHODS:The visual resolution measurements included high and low visual acuities and contrast sensitivity functions.These tests were conducted under photopic and then mesopic conditions.Twenty-one Sjögren’s syndrome patients and 21 aged-matched healthy volunteers completed all the measurements in this study.RESULTS:Sjogren’s syndrome patients have greater impairment in contrast sensitivity than standardized visual acuity.This reduction was significant under the mesopic condition.Also,Sjogren’s syndrome patients treated with pilocarpine suffer more than patients without pilocarpine treatment under low light conditions.CONCLUSION:Sjogren’s syndrome patients shows greater impairment in different visual resolution tasks due to dry eye symptoms.

Hypergammaglobulinemic purpura of waldenstorm associated with sjogren’s syndrome in a young female responding to rituximab treatment

Hypergammaglobulinemic Purpura of Waldenstorm is one of the uncommon conditions with purpura and is often associated with collagen vascular disease. It is difficult to treat and sometimes needs anti CD 20 molecules for resistant cases.

A case of recurrent rhabdomyolysis associated with childhood Sjogren’s syndrome

We report a 9-year-old Japanese girl who presented with muscle weakness and elevated serum levels of muscle-derived enzymes following mycoplasma infection. Rhabdomyolysis or myositis was suggested by magnetic resonance imaging and repeated four times within 4 years. Each episode developed following respiratory infection and spontaneously recovered. The diagnosis of Sjogren’s syndrome was made by decreased salivary secretion, MR sialography, lip biopsy, and positive anti-SSA/Ro antibody. Given the rarity of rhabdomyolysis/myositis, recurrent episode could be induced by infectious disease on the basis of underlying Sjogren’s syndrome. Conclusion: Sjogren’s syndrome should be considered as an underlying disease of recurrent infection-induced rhabdomyolysis/ myositis.

Comparison of corneal biomechanics in Sjogren's syndrome and non-Sjogren's syndrome dry eyes by Scheimpflug based device

AIM：To compare the corneal biomechanics of Sj？gren＇s syndrome（SS） and non-SS dry eyes with Corneal Visualization Scheimpflug Technology（CorV is ST）.METHODS：Corneal biomechanics and tear film parameters, namely the Schirmer I test value, tear film break-up time（TBUT） and corneal staining score（CSS） were detected in 34 eyes of 34 dry eye patients with SS（SSDE group） and 34 dry eye subjects without SS（NSSDE group） using CorV is ST. The differences of the above parameters between the two groups were examined, and the relationship between corneal biomechanics and tear film parameters were observed. RESULTS：The differences in age, sex, intraocular pressure（IOP） and central corneal thickness（CCT） were not significant between the two groups（P〉0.05）. The tear film parameters had significant differences between the SSDE group and NSSDE group（all P〈0.05）. Patients in the SSDE group had significantly lower A1-time and HC-time, but higher DA（P=0.01, 0.02, and 0.02, respectively） compared with the NSSDE group. In the SSDE group, DA was negatively correlated with TBUT（rho=-0.38, P=0.03）; HC-time was negatively correlated with CSS（rho=-0.43, P=0.02）. In the NSSDE group, HC-time was again negatively correlated with CSS（rho=-0.39, P=0.02）.CONCLUSION：There are differences in corneal biomechanical properties between SSDE and NSSDE. The cornea of SSDE tends to show less ＂stiffness＂, as seen by a significantly shorter A1-time and HC-time, but larger DA, compared with the cornea of NSSDE. Biomechanical parameters can be influenced by different tear film parameters in both groups.

Higher frequency of brain abnormalities in neuromyelitis optica spectrum disorder patients without primary Sjogren's syndrome

Neuromyelitis optica spectrum disorder often co-exists with primary Sjogreffs syndrome. We compared the clinical features of 16 neuro- myelitis optica spectrum disorder patients with （n = 6） or without primary Sjogreffs syndrome （n = 10）. All patients underwent extensive clinical, laboratory, and MRI evaluations. There were no statistical differences in demographics or first neurological involvement at onset between neuromyelitis optica spectrum disorder patients with and without primary Sjogren＇s syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinudear autoantibody, anti-Sjogren＇s-syndrome-related antigen A an- tibodies, anti-Sjogren＇s-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sjogren＇s syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67% （4/6） of patients with primary Sjogren＇s syndrome and in 60% （6/10） of patients without primary Sj6gren＇s syndrome. More brain abnormalities were observed in patients without primary Sj6gren＇s syndrome than in those with primary Sj6gren＇s syndrome. Segments lesions （〉 3 centrum） were noted in 50% （5/10） of patients without primary Sj6gren＇s syndrome and in 67% （4/6） of patients with primary Sjogren＇s syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sjogren＇s syndrome are similar. However, neu- romyelitis optica spectrum disorder patients without primary Sjogreffs syndrome have a high frequency of brain abnormalities.

Gastrointestinal microbiome and primary Sjogren’s syndrome: a review of the literature and conclusions

The recognition of the profound impact of the human gastrointestinal microbiome(GM) on human autoimmune diseases has gradually increased thanks to deeper research efforts. As a systemic autoimmune disease, primary Sjogren’s syndrome(pSS) cannot be completely cured. Human studies have revealed that GM species and diversity are altered in patients with p SS compared with healthy individuals. Animal studies have provided possible mechanisms for the association between pSS and GM. The potential role of GM in pSS is exerted through several mechanisms. GM dysbiosis leads to increased intestinal permeability, which increases the risk of GM antigen exposure and activates specific autoreactive T lymphocytes via “molecular mimicry”. In addition, GM antigen exposure and intestinal immune tolerance loss caused by GM dysbiosis together induce chronic local gut mucosal inflammation, which deteriorates to systemic chronic non-specific inflammation with the circulation of pro-inflammatory lymphocytes and cytokines. These factors eventually activate autoreactive B lymphocytes and lead to pSS. If GM plays a key role in the pathogenesis of pSS, clarifying the underlying mechanisms will be helpful for the development of new therapies targeting GM for dry eye associated with pSS. This review summarizes the latest knowledge about the relationship between GM and p SS,with the aim of contributing to future research and to the development of new clinical applications.

Pulmonary amyloidosis and multiple myeloma mimicking lymphoma in a patient with Sjogren’s syndrome:A case report

BACKGROUND Sjogren’s syndrome(SS),which affect salivary gland function,is an autoimmune disease.SS may involve extraglandular organs.Approximately 10 to 20 percent of SS patients have clinically significant lung disease,but presentation of pulmonary amylodosis is extremly rare.The incidence of benign monoclonal gammopathy in SS patients is high,but multiple myeloma is rare.No case involving the simultaneous occurrence of two rare diseases,pulmonary amyloidosis and multiple myeloma,in the same patient with SS has been reported so far.CASE SUMMARY A 41-year-old male patient was referred to our hematology department due to incidentally detected gastric plasmacytoma.He had been diagnosed with SS four years earlier.Multiple miliary nodules,ground glass opacity in both lung fields,and enlargement of both inguinal lymph nodes was observed on chest and abdomen computer tomography.Based on the pathological findings of lung and lymph node biopsied specimens,the patient was diagnosed with pulmonary amyloidosis and multiple myeloma.Pulmonary amyloidosis and multiple myeloma associated with SS has rarely been reported.CONCLUSION This is an extremely rare case of simultaneous pulmonary amyloidosis and multiple myeloma in the same patient with SS.

NF-κB Controls Resistance of Human Salivary Gland (HSG) Cells to Apoptosis in an <i>in Vitro</i>Model of Sjogren’s Syndrome

Aim: To elucidate the anti-apoptotic properties of nuclear factor kappa light-chain-enhancer of activated B cells (NF-κB) and feedback regulation of NF-κB by nuclear factor of kappa light-chain-enhancer of activated B-cells inhibitor alpha (IκBα). Methods: We developed an in vitro model of Sjogren’s syndrome by transfecting human salivary gland (HSG) and acinar cells (NS-SV-AC) with a plasmid-encoding IκBαM (pCMV-IκBαM), a degradation-resistant IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha)-mutant, and examined TNF-induced apoptosis and anti-apoptotic properties of NF-κB. Apoptosis and induction of pro-apoptotic and anti-apoptotic genes were investigated by cDNA arrays, RT-PCR, electrophoretic mobility shift assays, and western blot. Results: In the presence of NF-κB inhibitors, TNF-induced apoptosis was markedly increased in both salivary gland and acinar cells. Increased caspase-3 activity was present in both HSG and NS-SV-AC cells. IκBαM-transfected salivary gland cells were more sensitive to TNF-induced apoptosis than IκBαM-transfected acinar cells. Transcription of pro-apoptotic genes was confirmed in both HSG and NS-SV-AC cells that were transfected with IκBαM. Results from caspase-3 activity assay confirmed previous experiments showing an apoptotic role for NF-κB. Conclusion: Data from gene expression arrays suggest that different mechanisms may operate during TNF-induced apoptosis in salivary gland ductal and acinar cells.

Primary Sjogren’s syndrome and focal proliferative and crescentric necrotizing glomerulonephritis

Intro: Primary Sjogren’s syndrome is a chronic systemic autoimmune disease. Although ocular and oral dryness are the hallmarks of this syndrome, renal involvement when present most commonly has the histological appearance of tubointerstitial nephritis and less often glomerular involvement. We report, a unique case of renal manifestations of primary Sjogren’s syndrome with a proven histological focal proliferative and crescentric necrotizing glomeru-lonephritis. Case: A 30 years old man with Kimura disease presented with four months of subjective fevers, migrating skin erythema, dry mouth, and dry eyes. On further workup the patient was found to have a positive ANA, positive anti-SSA, and was evaluated by ophthalmology who found keratoconjunctivitis sicca. The patient was started on hydroxychloroquine in combination with prednisone. On follow up, the patient was found to be hypertensive with acute kidney injury, a creatinine of 3.65, proteinuria and hematuria. Renal ultrasound was unremarkable. Cytoplasmic ANCA was positive and kidney biopsy was performed revealing non pauci-immune focal proliferative and necrotizing glomerulonephritis with cellular crescents and mesangial dense deposits by electron microscopy. Conclusion: To our knowledge, the association between biopsy proven focal proliferative and necrotizing glomerulonephritis with primary Sjogren’s syndrome has never been previously described in the literature, nor has there been a reported case of association between Kimura disease, ANCA serology and primary Sjogren’s syndrome.

Hypokalemic Paresis Revealing a Primary Sjogren’s Syndrome

Hypokalemic acidosis can complicate a primary Sj&ouml;gren’s syndrome. The clinical feature is rarely revealed by manifestations due to hypokalemia. We report the case of a 46-year-old woman, admitted to explore a paresthesia and paresis of inferior limbs. The diagnosis of Sj&ouml;gren’s syndrome was retained since there was the association of xerophthalmia, sialadenitis at the labial biopsy and positive immunological results (anti-SSA and anti-SSB). The absence of another auto-immune or systemic illness allowed us to consider that the Sj&ouml;gren’s syndrome was primary. The biological explorations revealed a hyperchloremic and hypokalemic acidosis. The treatment was based on corticosteroid and potassium supplementation. The follow-up was marked by a clinical and biological amelioration.

A Case Report of Mesenteric Panniculitis and Primary Sjogren’s Syndrome

Mesenteric Panniculitis is a benign fibro-inflammatory process involving adipose tissue of the mesentery. It is characterised by fat necrosis, chronic inflammation and fibrosis, causing thickening and shortening of the mesentery. Patients may present with localised abdominal pain, abdominal mass, intestinal obstruction and ischaemic colitis. We report a case of mesenteric panniculitis causing abdominal pain in a patient with active Primary Sjogren’s Syndrome. The rarity of this case makes it of interest. We review the current literature on mesenteric panniculitis and its association with connective tissue disease and inflammatory conditions. A 64-year-old Caucasian male presented in 1994 with dry mouth. A diagnosis of Primary Sjogren’s Syndrome (PSS) was made on salivary gland biopsy. In 2010 he presented with an exacerbation of his eye symptoms, muscle pain and fatigue. He complained of abdominal pain and night sweating, but denied any weight loss or change in bowel habit. There was no significant past medical history other than PSS. On examination he had a small right submandibular node and mild synovitis at the right proximal interphalangeal joint and carpometacarpal joint. Examination of the abdomen showed marked umbilical tenderness but no organomegally. Blood tests at this time showed an active inflammation: CRP of 61 (NR 5 mg/L), ESR 39 (NR 20 mm/s), strongly positive ENA Ro and La. IgG was elevated at 18.6 (NR 5.8-15.4), Complement was low at 0.17 (NR 0.18-0.6). An abdominal ultrasound scan demonstrated a 6 × 3 ×3 cmarea of diffuse homogenous fat encasing some mesenteric vessels in the area of focal tenderness. CT abdomen and pelvis showed oedematous mesenteric fat and lymph nodes in the jejunal small bowel mesentery, consistent with mesenteric panniculitis. Laparoscopic biopsy was discussed with the surgical team, but was felt not indicated as risk outweighed potential benefit. The patient was treated with a 9-week reducing course of oral steroids. His abdominal symptoms resolved although CT abdomen showed little improvement in mesenteric panniculitis. A review of the literature suggests that currently there is no standard treatment and management should be guided by patient symptoms. Mesenteric Panniculitis is rare;as a result evidence for treatment is limited to individual case reports. There is no clear link between symptom improvement and radiological resolution of mesenteric panniculitis. It has, therefore been suggested that follow-up imaging should be limited to those with persistent symptoms. Overall the prognosis for mesenteric panniculitis is good, up to half of patients do not require treatment, and recurrence of symptoms is uncommon.

Tubulointerstitial Nephritis Complicated with Primary Sjogren’s Syndrome under Treatment for Type 2 Diabetes Mellitus

Tubulointerstitial nephritis complicated by primary Sj?gren’s syndrome in a patient under treatment for type 2 diabetes mellitus was diagnosed in the early stage of the disease by renal biopsy. The symptoms of primary Sj?gren’s syndrome, such as thirst and polydipsia, were masked by the characteristic symptoms of type 2 diabetes mellitus. An association between sicca symptoms and diabetes mellitus (types 1 and 2) has been previously reported. Hence, it is possible that there are common underlying immunological mechanisms between primary Sj?gren’s syndrome and diabetes mellitus of both types. Intervention with steroids in a timely manner appears to have prevented or slowed the progression of re- nal impairment.

Kikuchi-Fujimoto Disease in Patients with Sjogren’s Syndrome

Sjogren’s syndrome is a chronic autoimmune exocrinopathy associated with dry eyes and dry mouth as major clinical manifestations. It is characterized by lymphocytic infiltration of lacrimal and salivary glands and autoantibody production, especially anti-Ro (or SSA) and anti-La (or SSB). Lymphoproliferative disorders are a feature of Sjogren’s syndrome, and can be considered an extraglandular manifestation of the disease. Kikuchi-Fujimoto disease or histiocytic necrotizing lymphadenitis is a rare form of lymphadenitis. It is reported more often in young adult women with localized lymphadenopathy (usually cervical), fever, rashes, and leukopenia. It is a self-limiting disease with resolution within 1 - 4 months in almost all patients. Sjogren’s syndrome has been reported in patients with other systemic diseases including SLE and lymphomas. Here we present a patient with Kikuchi-Fujimoto disease who developed Sjogren’s Syndrome 8 years after her diagnosis of Kikuchi-Fujimoto disease.

原发性干燥综合征患者抗SSB与其他实验室参数相关性研究

目的探讨原发性干燥综合征(pSS)患者自身免疫性抗体抗干燥综合征B抗体(抗SSB)、抗干燥综合征A抗体(抗SSA)60、抗SSA52在疾病活动性评价中的价值。方法收集152例pSS患者临床资料及实验室数据进行回顾性分析,相关实验室数据包括血常规、C反应蛋白(CRP)、红细胞沉降率(ESR)、类风湿因子(RF)、免疫球蛋白(Ig)A、IgG、IgM、补体C3、补体C4、抗SSB、抗SSA60、抗SSA52,根据患者抗SSB、抗SSA60、抗SSA52检测结果进行分组统计分析。结果152例pSS患者中抗SSB患者阳性率为35.5%,抗SSA60患者阳性率为61.8%,抗SSA52患者阳性率为71.7%。抗SSB+患者红细胞计数(RBC)、血红蛋白(Hb)、白细胞计数(WBC)水平明显低于抗SSB-患者,ESR、IgG、RF水平明显高于抗SSB-患者(P<0.05);抗SSA60+患者年龄、WBC、血小板计数(PLT)明显低于抗SSA60-患者,IgG、RF水平明显高于抗SSA60-患者(P<0.05);抗SSA52+患者IgG、RF水平明显高于抗SSA52-患者(P<0.05)。抗SSB与抗SSA60、抗SSA52呈正相关(r=0.563、0.414,P<0.05)。结论抗SSB+pSS患者存在更严重的血液系统损伤,早期pSS患者应进行抗SSB检测并注意随访。

正常人与Sj(?)gren’s Syndrome患者球结膜免疫细胞的研究

目的 研究正常人与干燥综合征(Sjogren’s Syndrome,SS)患者球结膜HLA-DR+细胞、朗格罕斯细胞(LC)、T淋巴细胞亚群的变化特征。方法 采用链菌素-过氧化物酶法检测正常人与SS患者球结膜组织。结果 (1)SS患者球结膜大量T淋巴细胞浸润,抑制性T淋巴细胞(CD^(+8))较辅助性T淋巴细胞(CD^(+4))为多。CD^(+4)/CD^(+8)比值升高。(2)SS球结膜中LC数量减少,且鳞状上皮化生明显。(3)SS球结膜中HLA-DR^+细胞较正常人明显增加。结论 SS患者球结膜有显著的病理改变和免疫细胞异常。

Oral Candidiasis in Sjgoren's Syndrome：Prevalence，Clinical Features，and Treatment

This paper reports the diagnosis of 65 patients with Sjogren′s Syndrome. Among these patients, 20 patients(30.77%) were complicated with oral candidiasis. The twenty patients were treated by topical nystatin smearing, 2% sodium bicarbonate solution rinsing, and transfer factor injecting for about 2 months. The soreness, erythema, unpleasant feeling, angular cheilitis in mouths significantly diminished or completely disappeared, following two months treatments. The good results have been kept 6 months after follow up. However, dry mouth and atrophic changes, though showed no furture development, the therapeutic response was not significant.

CLINICAL APPLICATION AND EVALUATION OF SALIVA FERNING TEST IN SJGREN' S SYNDROME

Objective To evaluate the saliva ferning test (SFT) as diagnostic test for xerostomia in patients with Sjogren’s Syndrome (SS). Methods In this study, dried samples of freshly produced saliva from 78 patients with established SS according to European Community criteria and 80 healthy controls were examined by light microscopy. The crystallization was classified into 4 types according to the ferning phenomenon: uniformity, branching, spreading and integrity (type I normal and type Ⅱ,Ⅲ,Ⅳ abnormal ). Then, the 78 patients underwent lebial salivary gland biopsy. According to Tarpley’s classifica- tion, minor salivary gland biopsy (≥2 + ) was considered to be positive . Results 1. The sensitivity of SFT was high (70/ 78 = 89. 74% ). And the specificity wes also high (67/80 = 83. 75% ). 2. Abnormal SFT was observed in 70/78 (89. 74% ) samples from patients group and in 13 /80 (16. 25% ) samples from healthy controls. The differences of SFT in patients group versus controls were statistically significant (P< 0. 01 ). 3. The sensitivity of SFT and mini labial gland biopsy had no significant differences (P > 0. 05) as diagnostic tests in SS. Conclusion SFT was simple, sensitive and specific as diagnostic test in SS suspect patients just as mini labial gland biopsy.

抗Ro-52抗体与抗SSA抗体在自身免疫病中的检测意义

目的 探讨抗Ro-52 kDa自身抗体与抗SSA抗体的关系及其在中国人群中SLE和SS等自身免疫病的诊断价值.方法 收集自身免疫病患者血清,其中SLE 50例,SS 50例,其他自身免疫病30例,50例健康者血清作为对照,用免疫印迹法检测所有标本中抗Ro-52与抗SSA抗体,同时用间接免疫荧光法检测所有标本ANA核型.结果 抗Ro-52和抗SSA抗体阳性率在SLE患者中分别为60%和64%,在SS中分别为72%和82%,在其他自身免疫病患者中分别为30%和23.33%,均高于健康对照组（6%）,经χ2检验,差异有统计学意义（P＜0.05）.结论 抗Ro-52和抗SSA抗体阳性对诊断SLE和SS有一定的临床价值,二者的确切关系还需进一步探讨.