Reliability and validity analysis of the Chinese version of Evaluation of Ankylosing Spondylitis Quality of Life (EASi-QoL).

OBJECTIVE: We aimed to convert the English version of the Evaluation of Ankylosing Spondylitis Quality of life (EASi-QoL) into a Chinese version, and to test the reliability and validity of the Chinese version of EASi-QoL. METHODS: The EASi-QoL was translated into Chinese. A total of 127 patients with ankylosing spondylitis (AS) were evaluated using the Chinese version of EASi-QoL to test its validity and reliability. Internal and test-retest reliability was assessed. In addition, correlation and exploratory factor analyses evaluating the structural, convergent, and criterion-related validities of this measure were performed. RESULTS: The total Cronbach's α coefficient of the Chinese version of EASi-QoL was 0.911. The Kaiser-Meyer-Olkin value of the scale in this study was 0.917, and the Bartlett's test value was 2403.499. The convergent validity of the related domains was analyzed using confirmatory factor analysis; and the average variance extracted values corresponding to the four dimensions were all > 0.5, and the composite reliability values were all > 0.7. Discriminative validity analysis showed that the correlation between the four domains of EASi-QoL and their related domains of the depression/anxiety screening scale and the Medical Outcomes study Short-Form 36 were moderate to high. CONCLUSION: The Chinese version of EASi-QoL has high reliability and validity, and can reflect the impact of AS on the quality of life. Key Points • The Chinese version of EASi-QoL can accurately measure the impact of AS on the quality of life from the perspective of a patient. It is applicable to the evaluation of AS patients in China • The Chinese version of EASi-QoL is a scale with good reliability and validity.

Central diabetes insipidus unveiled by glucocorticoid therapy in a patient with an empty sella: A case report and literature review.

RATIONALE: Some diseases contribute to hypopituitarism without clinical manifestations and the glucocorticoid therapy may unveil central diabetes insipidus. The condition is rare and usually causes problems for clinical physicians. PATIENT CONCERNS: A 59-year-old woman presented to our hospital due to facial numbness and persistent eyelid heaviness. DIAGNOSIS: Physical examination and cerebrospinal fluid examination supported a diagnosis of Guillain-Barre[Combining Acute Accent] syndrome. Magnetic resonance imaging showed an empty sella. Hormone test indicated hypopituitarism. INTERVENTIONS: The patient received intravenous immunoglobulin and glucocorticoid. Central diabetes insipidus appeared after 20 days. Subsequently, the patient was prescribed 1-desamino-8-D-arginine vasopressin and prednisone. OUTCOMES: During 6 months' follow-up, the patient's urine output was gradually reduced to normal level. LESSONS: This case indicated that hypopituitarism may be caused by an empty sella and be masked by adrenal insufficiency. Central diabetes insipidus may present after glucocorticoid therapy.

[Diagnosis and Treatment of 43 Patients with IgG4-related Disease].

OBJECTIVE: To summarize the clinicopathological characteristics, diagnosis and treatment of IgG4-related disease (IgG4-RD). METHODS: The clinical data of 43 cases with IgG4-RD diagnosed from January 2013 to December 2017 were retrospectively analyzed. The clinical data of the patients including clinical characteristics, accessory examinations, diagnosis, and treatment were collected. RESULTS: Among the 43 patients with IgG4-RD, the ratio of male to female was 3∶1, the mean age was (51.3±15.9) years. Eleven patients had gastrointestinal symptoms, including 5 cases of IgG4-related cholangitis with the feature of dilation of the biliary system and narrowing of the lumen in the abdominal enhanced CT scans, and 6 cases of IgG4-related autoimmune pancreatitis with the feature of pancreatic enlargement or soft tissue density shadow in the abdominal enhanced CT scans. There were 10 cases (23.3%) with periorbital involvement, with the feature of intraorbital soft tissue nodule in the CT scan. Besides, 9 cases (20.9%) had lymphadenopathy, 6 cases (14.0%) had fever. The results of autoimmune antibody tests showed that 14 of 42 patients had increased antinuclear antibody (ANA). Among 40 patients who underwent immunoglobulin tests, 25 cases had elevated IgG, 12 cases had increased IgA, and 29 cases had increased IgE. Coombs test were performed for 6 cases and 4 patients were positive. Serum immunoglobulin G4 subtypes showed that the IgG4 levels of 35 patients were higher than 1 350 mg/L. The immunohistochemistry showed that IgG4 (+) cells (3->500/HPF) were infiltrated, with the CD20 (+), CD3ε (+) or CD138 (+). Among the 43 patients, 5 patients underwent operations due to misdiagnosis. All patients were treated with steroid and immunosuppressive agents after diagnosis, and their clinical symptoms were improved. CONCLUSION: The clinical symptoms of IgG4-RD are various, involving multiple organs. Therefore, the standardized diagnosis and treatment of IgG4-RD should be strengthened.

Successful closure of ileostomy in a patient with intestinal Behçet's disease after therapy with adalimumab: A case report.

RATIONALE: Behçet's disease (BD) is a chronic immune-mediated inflammatory disorder involving multiple organ systems. In BD, intestinal ulcers can present as a refractory lesion capable of perforation, which makes the choice of treatment difficult. PATIENT CONCERNS: A 34-year-old male who was diagnosed with intestinal BD and suffered with an ileocecal perforation. He underwent surgery for an ileostomy and was given corticosteroids as treatment. However, the ulcerative lesion remained resistant to the therapy that was provided which delayed the closure operation. DIAGNOSIS: Intestinal BD with severe post-operative complication. INTERVENTIONS: A course of adalimumab (ADa) therapy was started. Subsequently surgery was performed. And ADa and thalidomide were used as a maintenance therapy. OUTCOMES: In this case, a course of ADa therapy was given which healed the intestinal ulcers and allowed us to successfully perform the closure operation. LESSONS: This case indicates that ADa may be an effective treatment option in future cases, minimizing complications and allowing the closure operation to be performed successfully.

[Comorbidity of Autoimmune Diseases: a Field that Needs Multidisciplinary Attention].

Comorbidity of autoimmune diseases is a very important issue but easily ignored in the clinical practice. The treatment of comorbidity of autoimmune diseases needs cooperation of multiple disciplines,which is totally different from traditional clinical disciplines division and treatment mode. Based on the clinical features of the disease,we will comprehensively look through genetic,environmental,and immune factors involving in molecular and immunological compatibility pathogenesis,and also generalize common pathological features,such as immune complex deposition and accumulation of lymphocytes. We will also investigate the association and differences between the diseases with comorbidity,and explore the outcome and prognosis of comorbidity of autoimmune diseases. With clarify of the concept of autoimmune comorbidities,we hope bring more and more attention on this aspect,so as to improve the diagnosis,treatments as well as the prognosis of these diseases.

[A Retrospective Analysis of Clinical Features of Interstitial Pneumonia with Autoimmune Features].

OBJECTIVE: To analyze the clinical features of interstitial pneumonia with autoimmune features (IPAF) and the correlation between them. METHODS: We respectively analyzed the patients with interstitial lung disease (ILD) admitted in our hospital from January 2014 to January 2017. The patients who met all priori requirements and at least one feature of one domain were recuited, and the clinical features and autoimmune diseases related prognosis were analyzed. RESULTS: There were 90 patients recruited,including 38 patients completely met IPAF classification criteria and 52 patients who incompletely met. The average age was (62.34±14.98) yr.. The pneumonia pattern of complete IPAF patients was non-specific interstitial pneumonia (NSIP), while it was usually interstitial pneumonia (UIP) in the incomplete IPAF patients. During follow-up,11 patients were diagnosed with autoimmune diseases (4 with complete IPAF,and 7 with incomplete IPAF) . According to Cox regression analysis,completely meet the criteria of IPAF was related to the relapse of disease. CONCLUSION: There exist relation between IPAF and autoimmune diseases. The patients with IPAFmay finally develop into autoimmune diseases. The IPAF classification criteria provide basic structure for this disease,but the limitation of the criteria call for revising by more clinical trials.

[Clinicopathological Analysis of Autoimmune Hepatitis with Sjögren's Syndrome].

OBJECTIVE: To explore the biochemical-immune and pathological characteristics of autoimmune hepatitis (AIH) with Sjögren's syndrome (SS) . METHODS: A total of 76 cases of AIH patients were included from January 2009 to April 2017. Among them,there were 40 cases of AIH with SS and 36 cases without SS. The liver function,immunological index,histological features,length of first diagnosis and treatment costs were compared between the two groups. RESULTS: For AIH+SS group and AIH group,the proportion of women were 97.5% and 77.8%,the proportion of the first diagnosis age less than 60 years were 70% and 47.2%,the median course of disease were 30 months and 9 months,all the difference were statistically significant (P<0.05). The chief complaints in AIH+SS group and AIH group were as follows: cutaneous or scleracterus (52.5% vs. 38.9%),abnormal transaminase (17.5% vs. 44.4%),dryness of mouth and eye (15.0% vs. 2.8%),all the difference were statistically significant (P<0.05). There were no statistically significant difference in hospitalization expenses,and length of stay between the two groups (P>0.05). The median level of total bilirubin (TBIL),direct bilirubin (DBIL) and immunoglobulin (Ig) M of AIH +SS group were higher than those of AIH group,the mean level of albumin (ALB) and complement 3 (C3) of AIH +SS group were lower than those of AIH group,and the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) ,anti-Ro antibody A (SSA),anti-La antibody (SSB) and anti-soluble liver antigen antibody (SLA) of AIH+SS group were higher than those of AIH group (P<0.05). There were no statistically significant difference in histological changes of hepatocytes and bile duct injury rate (P>0.05). CONCLUSION: AIH patients in young and middle-aged women need to be vigilant with SS with main manifestation of skin sclera and high specific autoantibodies positive.

[Correlation of Thyroid Autoantibodies,System Lupus Erythematosus Immunologic Indicators and Disease Activity in SLE with HT].

OBJECTIVE: To investigate the correlation of disease activity and thyroid indicators ,immunologic markers of system lupus erythematosus (SLE) in SLE with Hashimoto's thyroiditis (HT). METHODS: The clinical data of 63 cases of SLE with HT were collected. According to Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2000),we classified the patients into four groups,which were remission group (5 cases),low (19 cases),moderate (12 cases) and high (27 cases) disease activity group. Each patient received the measurement of thyroid function indicators and autoantibodies,SLE immunologic indicators,serum complement (C3,C4),C-reactive protein (CRP),erythrocyte sedimentation rate (ESR), and routine blood test. The correlation of thyroid indicators,immunologic markers and disease activity were analyzed. RESULTS: The difference of free triiodothyronine (FT3) level in the four groups was statistically significant (P<0.05),and FT3 was negatively correlated with SLE disease activity (P=0.007) . There was no significant difference in other thyroid indicators and autoantibodies between the different groups (P>0.05). Negative correlation was found between FT3 level and anti-double-stranded DNA (dsDNA),level of anti-La antibody (SSB) and thyroid stimulating hormone (TSH) or thyroid peroxidase antibody (TPOAb). Thyroglobulin autoantibody (TgAb) was negatively related with C4,and positive correlation between FT3 and C3,FT4 and C4,TgAb and IgA. CONCLUSION: The pathogenesis of HT is associated with the disease activity in the patients of SLE with HT.

[Risk Factors of Respiratory Failure in the Dermatomyositis Patients with Interstitial Lung Disease].

OBJECTIVE: To reveal the clinical features of respiratory failure (RF) in dermatomyositis (DM) patients with interstitial lung disease (ILD),and to explore risk factors of RF in these patients. METHODS: The medical data of 122 DM patients with ILD were retrospectively reviewed: 40 developed RF (RF group),82 did not develope RF (Non RF group). Clinical,laboratory and radiological variables were compared between RF patients and Non RF patients. Multivariate Logistic regression was used to analyze risk factors of RF. RESULTS: In RF patients,the female-male ratio was 3∶1,the median age at DM onset was 49.5 (42.3-58.6) years-old. There were 67.5%,85.0% and 95.0% patients developed RF within 6 months,1 year and 2 years after the onset of DM. The factors significantly associated with RF included DM onset age,clinically amyopathic dermatomyositis (CADM),pneumomediastinum (PNM),aspartate aminotransferase(AST),lactate dehydrogenase (LDH),albumin,neutrophil-lymphocyte ratio,platelet-lymphocyte ratio,anti-Jo-1 antibody presence and ground-glass opacities sign (P<0.05). PMN and anti-Jo-1 antibody failed to be involved in logistic regression model. The regression analysis demonstrated that older DM onset age [odds ratio (OR)=1.791,P=0.025],higher AST level (OR=1.937,P=0.048),CADM diagnosis (OR=3.881,P=0.007) and ground-glass opacities sign (OR=4.187,P=0.014) were independent risk factors of RF in DM patients with ILD. CONCLUSION: RF occurs more often within 2 years of DM onset. The DM patients with older DM onset age,elevated AST level,CADM diagnosis or ground-glass opacities sign took higher risks for RF development.

[The Clinical Significance of Tumor-associated Antigens in Dermatomyositis Patients with Interstitial Lung Disease].

OBJECTIVE: To investigate the relationship between tumor related markers and the presence of interstitial lung disease (ILD) in dermatomyositis (DM) patients as well as potential serum markers for accompanied ILD. METHODS: Fifty-nine DM patients were included,including 30 patents with ILD. Serum level of anti-transcription intermediary factor1-γ (TIF1-γ) and tumor-associated antigens (TAAs) were detected to analyze the correlation of these markers with ILD. Meanwhile,the diagnostic value of these markers was evaluated by receive operating characteristic (ROC) curve analysis. RESULTS: We found that there were 5 patients bearing malignancies,independent from the presence of ILD (P=0.024). Serum anti-TIF1-γ was positive in 4/5 DM patients with tumor,of which sensitivity and specificity were 36.36% and 97.92%,respectively. In contrast,only one case was found positive anti-TIF1-γ in 30 DM with ILD (P=0.002).Carbohydrate antigen (CA)125,CA153,and cytokeratin-19 fragment (CYFRA21-1) were elevated in DM patients with ILD in compared to those without ILD. The area under curve (AUC) of CYFRA21-1 for the prediction of ILD was 0.745 (P=0.002). The optimal cut-off value was 3.58 ng/mL with a sensitivity of 60.71% and a specificity of 84.00%. The AUC in combination of CA125 and CYFRA21-1 could reach 0.801 (P<0.002) with a sensitivity of 64.29% and a specificity of 82.61%. CONCLUSION: Presence of malignance and positive anti-TIF1γ could be the protective factors for ILD in DM. Elevated serum levels of CA125,CA153,CYFRA21-1 could indicate the accompanying ILD.

DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC Culture.

Abnormal immune response of the body against substances and tissues causes autoimmune diseases, such as polymyositis, dermatomyositis, and rheumatoid arthritis. Irregular lipid metabolism and inflammation may be a significant cause of autoimmune diseases. Although much progress has been made, mechanisms of initiation and proceeding of metabolic and inflammatory regulation in autoimmune disease have not been well-defined. And novel markers for the detection and therapy of autoimmune disease are urgent. mTOR signaling is a central regulator of extracellular metabolic and inflammatory processes, while DEP domain-containing mTOR-interacting protein (DEPTOR) is a natural inhibitor of mTOR. Here, we report that overexpression of DEPTOR reduces mTORC1 activity in lymphocytes of human peripheral blood mononuclear cells (PBMCs). Combination of DEPTOR overexpression and mTORC2/AKT inhibitors effectively inhibits lipogenesis and inflammation in lymphocytes of PBMC culture. Moreover, DEPTOR knockdown activates mTORC1 and increases lipogenesis and inflammations. Our findings provide a deep insight into the relationship between lipid metabolism and inflammations via DEPTOR-mTOR pathway and imply that DEPTOR-mTOR in lymphocytes of PBMC culture has the potential to be as biomarkers for the detection and therapies of autoimmune diseases.

Identification of Palmitoleic Acid Controlled by mTOR Signaling as a Biomarker of Polymyositis.

Polymyositis (PM) is a chronic disease characterized by muscle pain, weakness, and increase in muscle-related enzymes, accompanied with inflammations in lymphocytes. However, it is not well understood how the molecular alternations in lymphocytes contribute to the development of polymyositis. The mechanistic target of rapamycin (mTOR) signaling is the central regulator of metabolism and inflammation in mammalian cells. Based on previous studies, we proposed that mTOR signaling may control inflammatory reactions via lipid metabolism. In this study, we aim to figure out the role of mTOR signaling in the development of polymyositis and identify novel biomarkers for the detection and therapy of polymyositis. After screening and validation, we found that palmitoleic acid, a monounsaturated fatty acid, is highly regulated by mTOR signaling. Inhibition of mTORC1 activity decreases palmitoleic acid level. Moreover, mTORC1 regulates the level of palmitoleic acid by controlling its de novo synthesis. Importantly, increased palmitoleic acid has been proven to be a marker of polymyositis. Our work identifies palmitoleic acid in peripheral blood mononuclear cells (PBMC) as a biomarker of polymyositis and offers new targets to the clinical therapy.

mTOR complex 1 signalling regulates the balance between lipid synthesis and oxidation in hypoxia lymphocytes.

Mammalian cells adapt to different environmental conditions and alter cellular metabolic pathways to meet the energy demand for survival. Thus, the metabolic regulation of cells under special conditions, such as hypoxia, should be precisely regulated. During the metabolic regulation, mammalian target of rapamycin (mTOR) plays a vital role in the sensing of extracellular stimulations and regulating intracellular adaptations. Here, we report that mTOR complex 1 (mTORC1) signalling is a central regulator of lipid homoeostasis in lymphocytes. In hypoxia, mTORC1 activity is reduced and shifts lipid synthesis to lipid oxidation. Moreover, knockdown tuberous sclerosis complex 1 (TSC1) constitutively activates mTORC1 activity and impairs the hypoxia-induced metabolic shift. Therefore, TSC1 knockdown enhances hypoxia-induced cell death. Re-inactivation of mTORC1 activity via rapamycin may resist hypoxia-induced cell death in TSC1 knockdown lymphocytes. Our findings provide a deep insight into mTORC1 in the metabolic balance of lipid synthesis and oxidation, and imply that mTORC1 activity should be precisely regulated for the lipid homoeostasis in lymphocytes.

Interleukin-2-inducible T-cell kinase expression and relation to disease severity in systemic lupus erythematosus.

BACKGROUND: Interleukin-2 inducible T-cell kinase (ITK) is expressed in T cells, and plays an important role in autoimmune inflammatory diseases through regulating the balance of Th17/Treg. However, its role in human systemic lupus erythematosus (SLE) remains unclear. The present study aims to measure the activation status of ITK in T cells from SLE patients and healthy controls, and identify its possible correlation to disease severity. We also discuss the serum levels of Th17, Treg related cytokines including IL-17, IL-21, IL-22, IL-10, analyzing correlation between ITK and Th17/Treg related cytokines. METHODS: Peripheral blood samples were drawn from 42 patients with SLE and 43 healthy blood donors, and the phosphorylation of ITK protein was studied in T cells using flow cytometry. In addition, serum levels of Th17/Treg related cytokines were studied with enzyme-linked immunosorbent assay (ELISA). RESULTS: Percentages of CD4+pITK+ T cells, CD8+pITK+ T cells were higher in SLE patients compared with controls, and were positively related to disease activity, some clinical and laboratory parameters. Percentages of CD4+pITK+ T cells, CD8+pITK+ T cells were more prominent in active SLE patients compared with less active patients. Serum levels of Th17 and Treg related cytokines were higher in patients compared with controls. CD4+pITK+ T cells were related to levels of IL-17, IL-21. CONCLUSION: These data indicate that increased ITK expression could act as a disease activity marker and as a risk factor for involvement in SLE, but it still needs further study to confirm.