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ID PMID Title PublicationDate abstract
31838639 Persistent serological activity in primary Sjögren's syndrome. 2020 Mar To assess the presence of persistent serological activity and its association with clinical outcomes in primary Sjögren's syndrome. Clinical charts of 275 patients were reviewed retrospectively. Persistent serological activity was defined as an increase IgG ≥ 1.6 mg/dL or globulins > 3.7 g/dL or diminished C3 < 52 mg/dL or C4 < 12 mg/dL at least during two consecutive visits during a year (index period). The ClinESSDAI at the index period and the cumulative ClinESSDAI and the SSDDI at the last medical appointment were scored. A total of 159 patients with complete serological data were included mostly women and median disease duration of 10.2 years. Persistent serological activity was identified in 85 patients (53.1%). Only 13 patients changed their status to serological inactivity though the follow-up. Comparison of patients with (n = 85) versus without persistent serological activity (n = 74) showed that the first group had a higher frequency of impaired non-stimulated salivary flow, anti-La/SSB antibody, and RF, as well as higher ClinESSDAI scores. The most affected domains were the constitutional, glandular, cutaneous, renal, and hematological domains. On logistic regression analysis, the RF (OR 6.4, 95% CI 1.8-22, p = 0.003), the renal (OR 12.8, 95% CI 1.7-92, p = 0.01), and the hematological involvement (OR 4.7, 95% CI 1.6-13.4, p = 0.004) remained associated. Half of the patients studied had persistent serological activity, being this status constant through the follow-up. Persistent serological activity was associated with positive RF and higher ESSDAI scores due to hematological and renal activity. Scoring serological activity is an important issue in SS patients.
31789250 Association between three autoimmune diseases: vitiligo, primary biliary cirrhosis, and Sj 2019 Nov Although the association of multiple autoimmune diseases has already been widely described, no reports of the association between vitiligo, primary biliary cirrhosis and Sjogren's syndrome were retrieved in the SciELO and PubMed databases. The authors describe the case of a female patient who was diagnosed with primary biliary cirrhosis and Sjogren's syndrome at age 54. At age 58, she developed vitiligo restricted to the face, associated with significant impairment of self-esteem and quality of life. Antinuclear antibody was negative at the onset of the condition, but became positive after phototherapy initiation. In general, the occurrence of multiple autoimmune diseases in the same patient is known as a mosaic of autoimmunity. However, specific mechanisms appear to interconnect primary biliary cirrhosis and Sjogren's syndrome, such as PDC-E2-mediated generalized epithelitis.
30755262 Adult-onset Still's disease biological treatment strategy may depend on the phenotypic dic 2019 Feb 12 OBJECTIVES: Adult-onset Still's disease (AOSD) phenotype appears to be dichotomized in systemic or chronic articular forms. As biologicals and particularly interleukin (IL)-1 and IL-6 blockers play a more and more prominent role in the treatment, their place requires clarification. This study aimed to identify factors predictive of treatment response to anakinra or tocilizumab and investigate whether the choice of biotherapy and delays in the initiation of biotherapy influenced the likelihood of steroid discontinuation. METHODS: A multicenter exploratory retrospective study included all patients diagnosed with AOSD and receiving biological treatments in three regional hospitals until 2018. Clinical and biological characteristics at diagnosis and treatment-related data were collected. The nonparametric Mann-Whitney test was used to perform univariate analysis for quantitative variables, and Fisher's exact test was used for qualitative variables. RESULTS: Twenty-seven patients were included. All but one patient achieved remission with either anakinra or tocilizumab. Treatment responses depended on disease phenotype: the presence of arthritis and a chronic articular phenotype were associated with a substantial response to tocilizumab with p = 0.0009 (OR 36 [2.6-1703]) and p = 0.017 (OR 10 [1.22-92.6]), respectively, whereas the systemic form and the absence of arthritis were associated with a substantial response to anakinra with p = 0.0009 (OR 36 [2.6-1703]) and p = 0.017 (OR 10 [1.22-92.6]), respectively. Tocilizumab increased the likelihood of corticosteroid withdrawal (p = 0.029) regardless of delays in initiation or when it was initiated relative to other treatment in the overall therapeutic strategy. CONCLUSION: This study highlights the therapeutic implications of the phenotypic dichotomy of AOSD and should help us better codify AOSD treatment.
30959220 The pipeline of targeted therapies under clinical development for primary Sjögren's syndr 2019 Jun To date, no immunomodulatory drug has proved efficacious in primary Sjögren's syndrome (pSS). In pSS, difficulties in drug efficacy assessment is related to the large spectrum of clinical involvements (glandular/extraglandular involvement), to the lack of correlation between symptoms of dryness and glandular function assessed by objective measurements, as well as between symptoms and systemic complications of the disease. Severe organ manifestations are generally treated by off-label therapies in accordance with current practice and guidelines for Systemic Lupus Erythematosus or other connective-tissue diseases. Despite a much greater understanding of the pathogenesis of pSS, modern drug development has resulted in no approval of therapy so far. In this study, we performed a systematic review of all targeted therapies under clinical development in pSS, in 17 main online registries of clinical trials. Our search identified 264 trials, from which 25 targeted therapies for pSS were included. The molecules under current clinical development for pSS target B cells (n = 4), T cells or T/B cells costimulation (n = 5), inflammatory cytokines or chemokines and their receptors (n = 5), intracellular signalling pathways (n = 7) and various other targets identified in pSS (n = 4). The current drug development pipeline in pSS may lead to valuable strategies for the treatment of this currently difficult-to-treat disease.
31316856 A Case of Severe Symptomatic Central Nervous System Sarcoidosis Secondary to Treatment wit 2019 Antitumor necrosis factor-α therapy has been used effectively in treatment of many inflammatory diseases such as rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease. There are increasing number of paradoxical reactions associated with this therapy that are being reported. We present the case of a 63-year-old male with psoriatic arthritis maintained on adalimumab and methotrexate (previous treatment trials of prednisone and leflunomide) who developed severe symptomatic sarcoidosis in the brain, liver, and lung. Upon discontinuation of adalimumab, the symptoms resolved but the imaging findings persisted. Although the development of sarcoidosis (usually in the lung, skin, and eyes) while on antitumor necrosis factor-α therapy is increasingly reported, the brain and liver are less commonly involved but should be borne in mind by physicians when extensive granulomatous lesions develop.
31561582 Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospe 2019 Sep 26 : Introduction: Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). The efficacy and safety of tofacitinib have been shown in several randomized clinical trials. The study presented here aimed to assess the clinical tolerability and effectiveness of tofacitinib among RA patients in real life. Methods: Consecutive patients between January 2015 and April 2017 with RA who fulfilled the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria were included in a prospectively designed analysis of retrospective data. Patients were initiated on tofacitinib 5 mg bid. The primary objective was to analyze the safety of tofacitinib in a real-life cohort. Safety was assessed by the reasons to stop tofacitinib during follow up and changes of liver enzymes, hemoglobin, and creatinine. The secondary outcome was to analyze the frequency of and time to achieve low disease activity (LDA) and remission as defined by 28 joint count disease activity score (DAS28). Results: A total of 144 patients were treated with tofacitinib. A total of 84.9% of patients were pre-exposed to at least one biological agent. The average DAS28 at the initiation of tofacitinib was 4.43. A total of 50.0% of patients were positive for rheumatoid factor and 49.0% for ACPA. The mean follow up was 1.22 years (range 10d-3.7a) after initiation of tofacitinib treatment. A total of 94 (64.4%) patients remained on tofacitinib during follow-up. The average time to stop tofacitinib was 190.0 days. Reasons to stop tofacitinib were: insufficient response (n = 23), gastrointestinal symptoms (n = 18), infection (n = 5), myalgia (n = 2), remission (n = 2), headache (n = 2), cough, blue finger syndrome, intolerance, heartburn, psoriasis, and increased liver enzymes (all n = 1). Increased alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) > 2× upper limit of normal (ULN) were detected in 3.3% and 4.4% of patients, respectively. Hemoglobin decrease of >10% was detected in 15.1% of the patients and decreased lymphocytes <500/μL in 3.4%. An increase of creatinine >20% was detected in 9.4% of patients. A total of 62.9% and 50.0% of the patients achieved low disease activity (LDA) or remission after a median of 319 and 645 days, respectively. These rates were significantly higher in patients naïve to biologic agents as compared to patients pre-exposed to biologics (LDA: naïve 100% 92 d, pre-exposed 57.0% 434 d, p ≤ 0.001; remission: naïve 86.7% 132 d, pre-exposed 44.1%, 692 d, p = 0.001). Conclusions: Tofacitinib is a safe and effective treatment option for patients with RA. Tofacitinib may induce high rates of LDA and remission in patients with active disease, even after the use of one or more biologics, though the rate appeared higher in patients naïve to biologics. Tofacitinib may be a valuable option in a treat-to-target approach. Our data demonstrate that Janus kinase (JAK) inhibitors are safe and efficacious in real life patients.
31182344 Serological screening for coeliac disease in patients with juvenile idiopathic arthritis. 2019 Jun BACKGROUND AND STUDY AIMS: Juvenile idiopathic arthritis (JIA) is characterized by autoimmune aetiology. A gene locus 4q27 related to rheumatoid arthritis, psoriatic arthritis, and coeliac disease is associated with susceptibility to JIA. There are reports indicating several patients with JIA had been diagnosed with CD. We aimed to assess the frequency of coeliac disease (CD) in patients with juvenile idiopathic arthritis (JIA). PATIENTS AND METHODS: This prospective study was carried out from October 2015 to August 2016 and included 96 patients with JIA. All patients were evaluated in terms of clinical and laboratory findings of CD. Levels of total IgA and tissue transglutaminase antibody (tTG) IgA were measured in all patients. Those with increased level of tTG IgA were further tested for anti-endomysium IgA antibodies (EMA). Gastroduodenoscopy were planned for a definite diagnosis of CD in patients with positive EMA. RESULTS: Of the 96 patients in our study, 34 (35.4%) had oligoarticular form of JIA, 29 (30.2%) had polyarticular form, 12 (12.5%) had ERA form, 11 (11.5%) had systemic form, and 10 (10.4%) had psoriatic form. Sixteen of our patients (16.6%) were not using any drugs during the study. Neither EMA IgA antibodies were analysed nor gastro-duodenoscopy was performed because no patients were positive for tTG IgA. There was no difference in terms of tTG levels between the patients using NSAIDs or other drugs. CONCLUSION: We did not find CD in children with JIA. Long term studies with more JIA patients are needed to provide more precise interpretation.
31412888 B7-H3 participates in human salivary gland epithelial cells apoptosis through NF-κB pathw 2019 Aug 14 BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disorder mainly characterized by exocrine gland injury. Costimulatory molecules play an important role in immune-regulatory networks. Although B7 family costimulatory molecules were previously discovered in human salivary gland epithelial (HSGE) cells in pSS, the effects of the B7 family member B7-H3 (CD276) have not been well elucidated. Thus, this study aimed to investigate the role and mechanism of B7-H3 in HSGE cells in pSS. METHODS: The expression of B7-H3, B7-H1, PD-1 in serum, saliva and salivary gland were examined by immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to test the expression and distribution of B7-H3, AQP5 and CK-8 in salivary gland tissues. Flow cytometry, Cell Counting Kit 8 (CCK-8) and western blot (WB) were performed to research the apoptotic, proliferative and inflammatory effects of B7-H3 in primary HSGE cells and HSGE cell lines. RESULTS: Our results showed that the expression of PD-1, B7-H1 and B7-H3 in peripheral blood, and salivary glands in pSS patients was higher than that in healthy controls, which was positive correlation with the grade of the salivary glands. The expression of B7-H3 in saliva was higher in pSS patients than that in healthy controls, which was detected with the most significant difference of them. The expression of B7-H3 in primary HSGE cells of pSS patients was significantly higher than healthy controls. B7-H3 increased activity of NF-κB pathway and promoted inflammation of HSGE cells, decreasing the expression of AQP5. Furthermore, B7-H3 overexpression inhibited proliferation and induced apoptosis in HSGE cell lines. CONCLUSION: B7-H3 could promote inflammation and induce apoptosis of HSGE cells by activating NF-κB pathway, which might be a promising therapeutic target for pSS.
31368254 Characteristics and risk factors for pulmonary arterial hypertension associated with prima 2019 Sep AIM: This study aimed to retrospectively describe 15 new primary Sjögren's syndrome-pulmonary arterial hypertension (pSS-PAH) cases confirmed by right heart catheterization (RHC). Demographic and clinical characteristics were analyzed and risk factors for PAH in pSS were explored. METHOD: We retrospectively described 15 new pSS-PAH cases confirmed by RHC referred to our institution between January 2013 and March 2018. We present PAH and pSS characteristics, hemodynamic evaluations, medical management, and outcomes. A matched case control study was carried out to determine the risk factors of PAH in pSS compared with pSS-non-PAH patients. RESULTS: All patients were female with a mean age at PAH diagnosis of 52.9 ± 14.6 years. The delay between the first symptom and PAH diagnosis was 18.7 ± 19.7 months. The most common primary manifestation at PAH onset was exertional dyspnea (13/15). At diagnosis of PAH, PAH was severe with a mean pulmonary artery pressure of 48.8 ± 13.7 mm Hg (range, 27-72 mm Hg) and a mean cardiac index of 2.3 ± 0.6 L/min/m(2) (range, 1.47-3.41 L/min/m(2) ). Compared with the pSS-PAH without pericardial effusion, pSS-PAH with pericardial effusion had larger right arterial (53 [45-56.75] vs 38 [35.5-46.5], P = .018) and right ventricular sizes (47 [42.75-51.25] vs 36 [32.5-41], P = .007). Compared with the pSS non-PAH group, we identified 2 risk factors for PAH in pSS: pericardial effusion (odds ratio [OR] [95% CI], 14.29 [1.14-166.67], P = .039) and liver involvement (OR [95% CI], 14.71 [1.14-166.67], P = .035). CONCLUSION: For pSS patients, PAH can be the first manifestation. We believe that systemic evaluation, especially in patients with pericardial effusion and liver involvement, is important to identify high-risk patients for PAH, improving their prognosis.
31412077 Correction: Prevalence and predictors for sustained remission in rheumatoid arthritis. 2019 [This corrects the article DOI: 10.1371/journal.pone.0214981.].
31788158 Total Elbow Arthroplasty: Clinical Outcomes, Complications, and Revision Surgery. 2019 Dec Total elbow arthroplasty is a common surgical procedure used in the management of advanced rheumatoid arthritis, posttraumatic arthritis, osteoarthritis, and unfixable fracture in elderly patients. Total elbow prostheses have evolved over the years and now include the linked, unlinked, and convertible types. However, long-term complications, including infection, aseptic loosening, instability, and periprosthetic fracture, remain a challenge. Here, we introduce each type of implant and evaluate clinical outcomes and complications by reviewing the previous literature.
31139950 Associations of cigarette smoking with disease phenotype and type I interferon expression 2019 Sep Several studies have shown a negative association between smoking and primary Sjögren's syndrome (pSS), and smoking may interfere with the immune response. The purpose of this study was to investigate if smoking affects disease activity and disease phenotype in pSS. In this cross-sectional study, consecutive pSS patients filled out the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) form and a structured questionnaire regarding smoking habits. EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) scores were calculated and blood samples were analysed for type I interferon signature using RT-PCR. Of 90 patients (93% women, median age 66.5 years), 72% were type I IFN signature positive and 6, 42 and 53% were current, former and never smokers, respectively. No significant differences by smoking status were found regarding ESSDAI total score, activity in the ESSDAI domains or type I IFN signature. Patients with a higher cumulative cigarette consumption (≥ median) had higher scores in ESSPRI total [5.0 (3.0-6.3) vs 8.0 (6.0-8.3); p < 0.01] and ESSPRI sicca and pain domains. Comparing type I IFN signature negative and positive patients, the latter had significantly lower activity in ESSDAI articular domain (7/25 vs 3/64; p < 0.01) and lower scores in ESSPRI total [7.7 (5.2-8.2) vs 6.0 (4.0-7.7); p = 0.04]. Smoking was not associated with disease phenotype although patients with a higher cumulative cigarette consumption had worse symptoms in some disease domains. Current smokers were few making it difficult to draw any firm conclusions about associations to current smoking.
31888893 Primary Sjogren's syndrome: a great masquerader. 2019 Dec 29 A 41-year-old woman presented with paresthesia and inability to walk for 7 days. She had history of fatigue, polyarthralgia and difficulty in swallowing food for the last 1 year. She became edentulous over the last 5 years and wore dentures for the same. She appeared pale, emaciated and had oral thrush. She had areflexic quadriparesis with weakness more in lower limbs compared with upper limbs. With the initial diagnosis of Guillian-Barre syndrome, she was given five cycles of plasmapheresis following which there was a significant improvement in power. Sjogren's syndrome was suspected based on edentulous state in a middle-aged woman with multisystem involvement. Evaluation with Schirmer's test, parotid scintigraphy and labial minor salivary gland biopsy confirmed the diagnosis. She was treated with steroids following which a dramatic improvement in haemoglobin and total leucocyte count was noted. We report a varied presentation of primary Sjogren's syndrome.
31234583 Amelioration of Experimentally Induced Arthritis by Reducing Reactive Oxygen Species Produ 2019 Jun 23 Accumulated evidence suggests a pathogenic role of reactive oxygen species (ROS) in perpetually rheumatoid joints. Therefore, the application of radical scavengers for reducing the accumulation of ROS is beneficial for patients with rheumatoid arthritis (RA). We synthesized water-soluble fullerenols that could inhibit the production of ROS and applied intra-articular (i.a.) injection in an experimental arthritis model to examine the anti-arthritic effect of the synthesized compound. RAW 264.7 cells were used to examine the activity of the synthesized fullerenol. Collagen-induced arthritis (CIA) was induced in Sprague-Dawley rats by injecting their joints with fullerenol. The therapeutic effects were evaluated using the articular index as well as radiological and histological scores. Dose-dependent suppression of nitric oxide (NO) production caused by the fullerenol was demonstrated in the RAW 264.7 cell culture, thus confirming the ability of fullerenol to reduce ROS production. In the fullerenol-injected joints, articular indexes, synovial expression of ROS, histological and radiological scores, pannus formation, and erosion of cartilage and bone were all reduced. Moreover, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) levels were reduced, and fewer von Willebrand factor (vWF)-stained areas were identified in the fullerenol-treated joints than in control joints. The i.a. injection of fullerenol for reducing ROS production can ameliorate arthritis in joints by suppressing pro-inflammatory cytokine production and the angiogenesis process. Thus, the i.a. injection of fullerenol for reducing the production of ROS can be used as a pharmacological approach for RA patients.
31270382 Whole-Volume ADC Histogram Analysis in Parotid Glands to Identify Patients with Sjögren's 2019 Jul 3 At present, no gold standard for diagnosing Sjögren's syndrome (SS) is available in clinical practice. The 2002 American-European Consensus Group classification criteria are used to diagnose SS. Clinically, it is challenging to distinguish patients with SS from suspected patients undergoing different therapies. A total of 52 patients with SS and 24 patients suspected of having the disease prospectively underwent 3.0-T magnetic resonance (MR) scanning, including diffusion-weighted imaging (b = 0 and 1000 s/mm(2)). The whole-volume apparent diffusion coefficient (ADC) histogram analysis generated ADC(mean), skewness, kurtosis, and entropy values from bilateral parotid glands. Continuous variables were compared using an independent two-sample t test, and categorical variable compared using the Fisher's test between the two groups. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of the indexes. Fisher's tests demonstrated that some clinical indexes and MR morphology grades differed significantly between patients with SS and patients suspected of having the disease (all P ≤ 0.001). The parotid entropy value of patients with SS was significantly higher than that of patients suspected of having the disease (P < 0.001). Among MR parameters, entropy combined with kurtosis performed the best in differentiating patients with SS from those suspected of having SS (area under the ROC curve = 0.955). A whole-volume ADC histogram analysis might provide a series of parameters that reflect tissue characteristics.
31023369 Distal renal tubular acidosis and severe hypokalemia: a case report and review of the lite 2019 Apr 26 BACKGROUND: Distal renal tubular acidosis is a relatively infrequent condition with complex pathophysiology that can present with life-threatening electrolyte abnormalities. CASE PRESENTATION: We describe a case of a 57-year-old Caucasian woman with previous episodes of hypokalemia, severe muscle weakness, and fatigue. Upon further questioning, symptoms of dry eye and dry mouth became evident. Initial evaluation revealed hyperchloremic metabolic acidosis, severe hypokalemia, persistent alkaline urine, and a positive urinary anion gap, suggestive of distal renal tubular acidosis. Additional laboratory workup and renal biopsy led to the diagnosis of primary Sjögren's syndrome with associated acute tubulointerstitial nephritis. After potassium and bicarbonate supplementation, immunomodulatory therapy with hydroxychloroquine, azathioprine, and prednisone was started. Nonetheless, her renal function failed to improve and remained steady with an estimated glomerular filtration rate of 42 ml/min/1.73 m(2). The literature on this topic was reviewed. CONCLUSIONS: Cases of renal tubular acidosis should be carefully evaluated to prevent adverse complications, uncover a potentially treatable condition, and prevent the progression to chronic kidney disease. Repeated episodes of unexplained hypokalemia could be an important clue for diagnosis.
31287800 Effect of Sjögren's syndrome on maternal and neonatal outcomes of pregnancy. 2019 Aug 27 Background Sjögren's syndrome (SS) is an autoimmune connective tissue disease affecting the body's moisture-producing glands. Some studies have linked SS to adverse maternal/neonatal outcomes, but sample sizes have tended to be small, with few outcomes examined. The purpose of this study was to evaluate the effect of SS on pregnancy outcomes for mother and neonate using a large dataset. Methods We carried out a retrospective cohort study of women who delivered between 1999 and 2014 using data from the Nationwide Inpatient Sample from the United States. SS categorization is based on ICD-9 coding. Baseline characteristics were compared in both groups and multivariate logistic regression was used to compare maternal and fetal outcomes of pregnancies in women with and without SS. Results The prevalence of SS in our population was 1.34 cases/10,000 births, with the rate increasing over the study period. Women with SS tended to be older, Caucasian and to have pre-existing comorbidities. Births to women with SS were at greater risk of pre-eclampsia [odds ratio (OR) 1.63, 95% confidence interval (CI) 1.34-1.99]; premature rupture of membranes (OR 1.28, 95% CI 1.04-1.57); preterm delivery (OR 1.56, 95% CI 1.34-1.81); cesarean delivery (OR 1.29, 95% CI 1.17-1.41); and venous thromboembolic events (OR 3.71, 95% CI 2.57-5.35). Infants of women with SS were more likely to have intrauterine growth restriction (IUGR) (OR 3.00, 95% CI 2.46-3.65); and congenital malformations (OR 3.26, 95% CI 2.30-4.62). Conclusion SS is a high-risk pregnancy condition associated with significant comorbidities and adverse maternal and fetal outcomes. Women with SS may benefit from increased surveillance during their pregnancies.
31138153 TI-C4d(+) group and vice versa. Peritubular capillary (PTC) C4d was scored as 0 (absent), 2019 May 28 BACKGROUND: To evaluate renal expression of C4d, a complement component in the classical/mannose binding lectin (MBL) pathway, in patients with primary Sjögren's syndrome (pSS)-associated renal impairments. METHODS: We retrospectively reviewed the clinical and pathological data from 39 patients with pSS presenting with renal impairments. C4d was examined in paraffin-embedded biopsy tissues using immunohistochemistry. Glomerular C4d positive was defined when > 75% glomeruli were globally stained. Tubulointerstitial C4d (TI-C4d) were scored semi-quantitatively as 0 (absent), 1 (spotty or weak), 2 (patchy) and 3 (diffuse). A TI-C4d score ≥ 2 was considered TI-C4d positive and included in the TI-C4d(+) group and vice versa. Peritubular capillary (PTC) C4d was scored as 0 (absent), 1 (0~10%, minimal), 2 (10%~ 50%, focal), and 3 (> 50%, diffuse). RESULTS: Glomerular C4d deposition was observed in all 8 patients with pSS-related membranous nephropathy (MN) without obvious C1q deposition. Two of 5 patients with mesangial proliferative glomerulonephritis and 1 of 2 patients with IgA nephropathy had mild mesangial C4d deposition. Sixteen patients (6 glomerular dominant and 10 tubulointerstitial dominant) presented TI-C4d score ≥ 2. Patients in the TI-C4d(+) group exhibited a higher serum creatinine level at the time of renal biopsy (TI-C4d(+) 132.5 [89.7, 165.5] vs. TI-C4d(-) 83.0 [70.7, 102.0] μmol/L, P = 0.008). PTC C4d was observed in 12 patients, with each of minimal, focal and diffuse staining being noted in 4 patients. CONCLUSIONS: The MBL pathway of complement activation was potentially involved in pSS-related MN. Tubulointerstitial C4d might be a pathological marker of severe renal injury in patients with pSS-related renal impairments.
30905840 Correlation of clinical symptoms and signs with conjunctival gene expression in primary Sj 2019 Jul PURPOSE: The aim of this study was to characterize the expression of inflammation-related genes on the ocular surface of Sjögren syndrome (SS) patients and to evaluate their correlations with clinical symptoms and signs. METHODS: The study enrolled 30 patients with SS dry eye and 15 healthy controls. Symptoms were evaluated using OSDI questionnaire. The clinical signs were investigated using corneal fluorescein staining (CFS), tear breakup time (TBUT), Schirmer test and tear osmolarity measurement. Conjunctival superficial cells were collected using conjunctival impression cytology and total RNAs were extracted for analysis using the NanoString(®) nCounter technology. The Mann-Whitney nonparametric statistical test and Spearman correlations were used to explore the correlations between the up/downregulated genes and the clinical signs and symptoms. RESULTS: Twenty-seven genes were upregulated and 13 were downregulated with statistically significant fold changes ranging from 1.5 to 16.7 and 0.3 to 0.8, respectively. OSDI and CFS were the most significantly correlated parameters with 21 and 19 inflammatory genes, respectively. Among all the upregulated genes, 14 were positively correlated with both OSDI and CFS. Two downregulated genes (GNGT1, HSPB2) were negatively correlated with OSDI and CFS. IL1RN was the only gene positively correlated with the Schirmer test. CONCLUSIONS: These results highlight the differentially expressed genes in primary Sjögren syndrome and their relationships between the inflammatory genes expressed and the patient symptom score and corneal damage. The inflammatory genes implicated in SS-associated dry eye could be important tools to determine the pathophysiological profiles of SS and potentially useable as specific signatures.
28338753 Second Chance. 2019 Oct 24 My second career as a schizophrenia researcher will focus on infectious agents as a cause. It will include the collection of serial sera, cerebrospinal fluid, functional magnetic resonance imaging, and diffusion tensor imaging on a cohort of affected individuals over 20 years. Since I believe that the initial transmission of these agents occurs in childhood, I will also follow a cohort of children from birth to age 20. Additional projects will focus on rheumatoid arthritis, geographic case clusters, immigrants, and epidemiology.