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ID PMID Title PublicationDate abstract
24267197 Use of NSAIDs in treating patients with arthritis. 2013 Patients with rheumatic diseases, including rheumatoid arthritis and osteoarthritis, almost universally describe pain and stiffness as important contributors to reduced health-related quality of life. Of the treatment options available, NSAIDs are the most widely used agents for symptomatic treatment. NSAIDs are effective anti-inflammatory and analgesic drugs by virtue of their ability to inhibit biosynthesis of prostaglandins at the level of the cyclooxygenase enzyme. However, many of the adverse effects of NSAIDs are also related to inhibition of prostaglandin production, making their use problematic in some patient populations. For the clinician, understanding the biology of prostaglandin as it relates to gastrointestinal, renal, and cardiovascular physiology and the pharmacologic properties of specific NSAIDs is key to using these drugs safely. Of particular importance is the recognition of co-morbid conditions and concomitant drugs that may increase the risk of NSAIDs in particular patients. In patients with risk factors for NSAID toxicity, using the lowest dose of a drug with a short half-life only when it is needed is likely to be the safest treatment option. For those patients whose symptoms cannot be managed with intermittent treatment, using protective strategies is essential.
27790030 Profile of ustekinumab and its potential in the treatment of active psoriatic arthritis. 2014 Psoriatic arthritis (PsA) is a chronic inflammatory arthritis and considered to be a less severe condition than rheumatoid arthritis. PsA patients have been treated for a long time with a number of different agents, from non-steroidal anti-inflammatory drugs to one or more disease-modifying antirheumatic drugs. In the last decade, recognition of the central role of tumor necrosis factor-alpha (TNFα) in the immunopathogenesis of many rheumatic diseases, including PsA, has led to the development of TNFα blockers. In PsA, these agents are uniquely efficacious in the treatment of different patterns of the disease, as well as slowing progression of erosive damage in the peripheral joints. However, a significant number of patients withdraw from therapy because of failure or poor tolerability. Among the novel therapeutic targets, interleukin (IL)-23/IL-12 has been investigated for the treatment of chronic inflammatory disease. In particular, ustekinumab is a human monoclonal antibody that prevents human IL-12 and IL-23 from binding to the IL-12Rβ1 receptor chain of IL-12 (IL-12Rβ1/β2) and IL-23 (IL-12Rβ1/23R) receptor complexes on the surface of natural killer cells and T-cells. Ustekinumab has been approved only for treatment of chronic plaque psoriasis, but also represents an interesting agent for treatment of PsA.
25514342 [Shape-memory osteosynthesis for trapeziometacarpal joint arthrodesis]. 2014 PURPOSE OF THE STUDY: Arthrodesis of the trapeziometacarpal joint is the method of choice in the treatment of degenerative arthritis of this joint. This procedure was indicated most frequently in middle-age patients doing hard manual labor. Methods for achieving a solid fusion of the trapeziometacarpal joint are known and often reported in the literature. Frequently, they are associated with some failure rate, particularly as concerns bone union. Our study presents a simple and effective method verified in cadaver specimens and then currently used at our department. MATERIAL AND METHODS: The procedure for arthrodesis of the trapeziometacarpal joint was verified fist in fixed wrist and hand specimens at the Institute of Anatomy, 1 st Faculty of Medicine, Charles University in Prague. If the original shape of the basal thumb joint between the trapezium and the metacarpal is maintained, it allows for correct reduction and subsequent arthrodesis in a required position. In patients, surgical treatment included the use of implants, two DePuy shape-memory staples, which facilitate sufficient fragment compression and provide stable fixation. The staples were inserted in pre-drilled and gauged tunnels in the body of the trapezium and in the proximal metaphysis of the fist metacarpal. RESULTS: Between 2011 and 2014, the procedure was used in 14 patients diagnosed with primary arthritis of the trapeziometacarpal joint. The group comprised nine women and five men, the average age was 52 years and the range was 44 to 69 years. Surgery was most frequently carried out on the dominant upper extremity (85%); there was no bilateral surgery. The average follow-up was 18.3 months (range, 5 to 39 months). Solid fusion was recorded at 7 weeks after surgery in all patients except for the one still treated at the time of this paper submission. All patients were free of pain, ten reported satisfaction with grip strength and hand function, the rest would have preferred improvement in fine motor skills of the thumb. All of them found the cosmetic appearance of the hand satisfactory.. DISCUSSION: The methods generally used for trapeziometacarpal joint arthrodesis are reported to carry some risk of pseudarthrosis development. A lot of modifications have been described, from conventional procedures using AO lag screws or Kirschner wires to up-to-date plate systems involving angle-stable fixation. Total fusion of the trapeziometacarpal joint is disputable in patients with rheumatoid arthritis from the technical point of view as well as the relevance of indication criteria. Some authors consider this procedure a contraindication for patients with rheumatoid arthritis. The use of joint replacement in treating trapeziometacarpal joint arthritis is another complex issue. CONCLUSIONS: An arthrodesis of the trapeziometacarpal joint based on careful assessment of indication criteria proved to be a simple, effective and low-cost method of stable osteosynthesis that provided good conditions for solid fusion of the trapezium with the base of the fist metacarpal. It allowed for sufficient abduction and opposition of the thumb, thus permitting satisfactory hand grip strength and full involvement in everyday life activities and occupations. It provided stability of the thumb, its painless movement and good cosmetic looks.
24391342 Anakinra for myocarditis in juvenile idiopathic arthritis. 2013 A 20-year-old pregnant woman with a history of juvenile idiopathic arthritis presented with flu-like symptoms, systemic inflammation with myocarditis, and severe cardiomyopathy. Six weeks earlier, her chronic-arthritis therapy had been changed from anakinra, an interleukin-1β receptor antagonist, to etanercept. When she resumed taking anakinra, her condition improved dramatically, including a complete recovery of ventricular function. Myocarditis is a well-recognized complication of systemic vasculitides. This unusual case emphasizes the important pathophysiologic role of interleukin receptors in the successful treatment of myocarditis. We suggest that clinical cardiologists be aware of the therapeutic usefulness of biological agents such as anakinra in patients with rheumatic conditions.
25049388 Denervation protects limbs from inflammatory arthritis via an impact on the microvasculatu 2014 Aug 5 Two-way communication between the mammalian nervous and immune systems is increasingly recognized and appreciated. An intriguing example of such crosstalk comes from clinical observations dating from the 1930s: Patients who suffer a stroke and then develop rheumatoid arthritis atypically present with arthritis on only one side, the one not afflicted with paralysis. Here we successfully modeled hemiplegia-induced protection from arthritis using the K/BxN serum-transfer system, focused on the effector phase of inflammatory arthritis. Experiments entailing pharmacological inhibitors, genetically deficient mouse strains, and global transcriptome analyses failed to associate the protective effect with a single nerve quality (i.e., with the sympathetic, parasympathetic, or sensory nerves). Instead, there was clear evidence that denervation had a long-term effect on the limb microvasculature: The rapid and joint-localized vascular leak that typically accompanies and promotes serum-transferred arthritis was compromised in denervated limbs. This defect was reflected in the transcriptome of endothelial cells, the expression of several genes impacting vascular leakage or transendothelial cell transmigration being altered in denervated limbs. These findings highlight a previously unappreciated pathway to dissect and eventually target in inflammatory arthritis.
23982178 Aryl hydrocarbon receptor and experimental autoimmune arthritis. 2013 Nov Aryl hydrocarbon receptor (Ahr) is thought to be a crucial factor that regulates immune responses. Many Ahr-mediated immune regulatory mechanisms have been discovered, which will likely enhance our understanding of the molecular pathogenesis of autoimmune inflammation including rheumatoid arthritis (RA). RA is a systemic inflammatory disease that affects approximately 1 % of the population and is characterized by chronic inflammation of the synovium and subsequent joint destruction. Recent findings showed that Ahr plays critical roles in the development of Th17 cells, which are key effector T cells in a variety of human autoimmune diseases including RA. Consistent with these findings, our previous study demonstrated that Ahr in T cells is important for the development of collagen-induced arthritis, a widely used murine model of human RA, possibly via the induction of Th17 cells. In addition, Ahr is an attractive molecule because tobacco smoke is a well-known environmental risk factor for RA development and Ahr agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methyl cholanthrene, and benzo[a]pyrene, are major toxic components in cigarettes. This review summarizes recent findings on Ahr functions in immune cells in the context of RA pathogenesis during stimulation with smoking-derived ligands. We also discuss the potential link between Ahr and novel factors, such as microRNAs, in the development of RA, thereby providing further mechanistic insight into this autoimmune disorder.
24863298 Effect of diquafosol ophthalmic solution on the optical quality of the eyes in patients wi 2014 Dec PURPOSE: To investigate the short- and long-term effects of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye. METHODS: Sixteen eyes in 16 patients with mild or moderate aqueous-deficient dry eye were treated with 3% diquafosol ophthalmic solution. Ocular higher-order aberrations (HOAs) were measured with a wavefront sensor before and at 15 min after diquafosol instillation at the baseline visit and at 4 weeks after treatment initiation. Dry eye symptoms, tear break-up time (BUT), corneal/conjunctival fluorescein staining and Schirmer's test were also evaluated before and after treatment with diquafosol. RESULTS: Treatment with diquafosol ophthalmic solution significantly improved dry eye symptoms, corneal staining and BUT. Compared with mean total HOAs at baseline (0.180 ± 0.06 μm), those at 4 weeks after treatment significantly decreased (0.148 ± 0.039 μm; p = 0.035), whereas those 15 min after diquafosol instillation at the baseline visit did not change significantly (0.170 ± 0.049 μm; p = 0.279). CONCLUSIONS: Although no significant change in HOAs was observed as a short-term effect of a single-drop instillation of diquafosol, long-term use of diquafosol to treat aqueous-deficient dry eye reduced HOAs as well as improved corneal epithelial damage and tear film stability.
24791507 [Effect of nourishing Yin, strengthening Qi and activating blood decoction on Fas/FasL in 2013 Dec OBJECTIVE: To observe the effect of nourishing Yin, strengthening Qi and activating blood decoction on Fas/FasL in salivary glands of NOD mice with Sjogren's syndrome and their mRNA expression. METHOD: Thirty-two NOD mice were randomly divided into the model group, the traditional Chinese medicine group (TCM group, orally given 0.4 mL nourishing Yin, strengthening Qi and activating blood decoction as per 100 g x kg(-1) everyday), the hydroxychloroquine group (given 0.4 mL hydroxychloroquine as per 60 mg x kg(-1) everyday), the traditional Chinese medicine and western medicine group (TCM WM group, given nourishing Yin, Strengthening Qi and activating blood decoction 50 g x kg(-1) and hydroxychloroquine 60 mg x kg(-1), 0.4 mL everyday), with eight mice in each group. Eight Balb/C mice were selected as the normal control group (normal group). All of mice were killed after eight weeks, and their submaxillary glands were dissected. The expression levels of Fas/FasL were examined by immunohistochemical method, and the FasL mRNA was detected by RT-PCR. RESULT: The expression levels of Fas/FasL in salivary glands of the model group were higher than that of other groups (P < 0.05). The expression level of FasL of the normal group was much lower than that in the hydroxychloroquine group (P < 0.05). The relative expression level of Fas mRNA in salivary glands of the model group was higher than that in other groups, but the control group was notably lower than other groups (P < 0.05). The expression level of FasL mRNA in salivary glands of the model group was higher than that in TCM and TCM WM groups (P < 0.05). But the expression level in TCM WM group was notably lower than the hydroxychloroquine group (P < 0.05). CONCLUSION: The nourishing Yin, strengthening Qi and activating blood decoction could down-regulate the expression level of Fas/FasL in salivary glands of NOD mice with Sjogren's syndrome and their mRNA expression, and had a better efficacy after being combined with hydroxychloroquine. The nourishing Yin, strengthening Qi and activating blood decoction might treat the Sjogren's Syndrome by reducing apoptosis which is regulated by Fas/FasL
24442883 Validation of EULAR primary Sjögren's syndrome disease activity (ESSDAI) and patient inde 2015 May OBJECTIVES: To validate the two recently developed disease activity indexes for assessment of primary Sjögren's syndrome (SS): the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI). METHODS: A prospective international 6-month duration validation study was conducted in 15 countries. At each visit, physicians completed ESSDAI, SS disease activity index (SSDAI), Sjögren's Systemic Clinical Activity Index (SCAI) and physician global assessment (PhGA); and patients completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and Discomfort (PROFAD) and patient global assessment (PGA). Psychometric properties (construct validity, responsiveness and reliability) were evaluated and compared between scores. RESULTS: Of the 395 patients included, 145 (37%) and 251 (64%) had currently active or current or past systemic manifestations, respectively. EULAR scores had higher correlation with the gold standard than other scores (ESSDAI with PhGA: r=0.59; ESSRPI with PGA: r=0.70). Correlations between patient and systemic scores were very low (ranging from 0.07 to 0.29). All systemic scores had similar large responsiveness in improved patients. Responsiveness of patient scores was low but was significantly higher for ESSPRI compared with SSI and PROFAD. Reliability was very good for all scores. CONCLUSIONS: ESSDAI and ESSPRI had good construct validity. All scores were reliable. Systemic scores had a large sensitivity to change in patients whose disease activity improves. Patient scores had a small sensitivity to change, however, significantly better for ESSPRI. Systemic and patient scores poorly correlated, suggesting that they are 2 complementary components that should be both evaluated, but separately.
24165505 Hypokalemic rhabdomyolysis: an unusual presentation of Sjogren's syndrome. 2013 Oct 28 Hypokalaemic rhabdomyolysis represents a medical emergency requiring rapid diagnosis and appropriate aetiological treatment. Renal tubular acidosis is a common cause of hypokalemia which can be idiopathic or secondary to systemic disorders such as Sjogren's syndrome. It can remain asymptomatic or manifest with metabolic abnormalities including hypokalemia paralysis, hypocalcaemia and hyperchloremic metabolic acidosis. Rhabdomyolysis presenting with severe hypokalemia as the first manifestation of Sjogren's syndrome is rare. We report a case of a 59-year-old woman who presented to our department with severe weakness of all limbs. Laboratory examination demonstrated hypokalemic rhabdomyolysis caused by distal renal tubular acidosis. Investigations revealed Sjogren's syndrome as the underlying cause of the metabolic disorders.
23617248 Effects of amino acids enriched tears substitutes on the cornea of patients with dysfuncti 2013 Sep PURPOSE: To evaluate the effect of aminoacid enriched artificial tears on the ocular surface of patients with dysfunctional tear syndrome (DTS). METHODS: Forty patients were divided into two groups: group 1 treated for 90 days with sodium hyaluronate (SH) 0.15% 1 drop × 5 times/day; group 2 treated for 90 days with SH 0.15% + aminoacids mixture 1 drop × 5 times/day. Symptom score questionnaire, tear break-up time (TBUT), corneal fluorescein stain, Shirmer's I test and confocal microscopy were performed at baseline and after 30 and 90 days. Confocal images underwent morphometric analysis. RESULTS: Both treatments improved symptoms after 1 month. Group 2 patients showed at 1 month an improvement of TBUT and corneal stain, maintained throughout the study. Also Shirmer's I test improved after 3 months. In group 1, an improvement of TBUT and corneal stain was observed after 3 months. The morphometric analysis of confocal images demonstrated at month 1 an improvement of nerve tortuosity in group 2; after 3 months both groups showed a significant improvement versus baseline. The epithelium showed, in both groups, a reduction in hyperreflective large cells starting from 1 month; the area of the cells was significantly reduced after 3 months, with a significant higher reduction in group 2. The perineural stromal opacity was significantly increased after 3 months, particularly in group 2. CONCLUSION: This is the first study addressing corneal changes after amino acids administration in a DTS population. The treatment with amino acids enriched SH can be considered a useful tool in the treatment of DTS.
25154742 Association of FCGR3A and FCGR3B copy number variations with systemic lupus erythematosus 2014 Nov OBJECTIVE: To determine whether copy number variations (CNVs) in FCGR3A and FCGR3B are associated with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Taiwanese individuals. METHODS: FCGR3A and FCGR3B CNV genotypes were determined in 846 patients with SLE, 948 patients with RA, and 1,420 healthy control subjects, using custom TaqMan CNV assays. The FCGR3A and FCGR3B CNV genotypes were compared between healthy control subjects and patients and among patients stratified according to clinical characteristics. RESULTS: A low (<2) FCGR3A copy number was significantly associated with SLE (for <2 copies versus 2 copies, P = 5.06 × 10(-4) , false discovery rate-corrected P [PFDR ] = 0.001, odds ratio [OR] 3.26, 95% confidence interval [95% CI] 1.68-6.35) and RA (for <2 copies versus 2 copies, P = 5.83 × 10(-4) , PFDR = 0.0012, OR 2.82, 95% CI 1.56-5.1). A low FCGR3B copy number was also significantly associated with SLE (for <2 copies versus 2 copies, P = 0.0032, PFDR = 0.0032, OR 1.59, 95% CI 1.17-2.18). Notably, a high (>2) FCGR3A copy number was also associated with SLE (for >2 copies versus 2 copies, P = 0.003, PFDR = 0.0061, OR 1.6, 95% CI 1.17-2.18). Additionally, the FCGR3A low copy number genotype was significantly enriched in subsets of patients with SLE (those with ulcer, arthritis, rash, discoid rash, photosensitivity, nephritis, leukopenia, thrombocytopenia, depressed complement levels, and autoantibody positivity) and patients with RA (those positive for rheumatoid factor) compared with healthy control subjects. The FCGR3B low copy number genotype was also significantly enriched in SLE patients with ulcer, rash, discoid rash, photosensitivity, ascites, nephritis, complement level depression, and anti-double-stranded DNA antibody positivity compared with control subjects. However, FCGR3B CNVs were not associated with RA susceptibility (for <2 copy numbers versus 2 copy numbers, P = 0.3584, OR 1.15, 95% CI 0.85-1.55) and clinical characteristics. CONCLUSION: In Taiwanese individuals, a low FCGR3A copy number is a common risk factor for SLE and RA, while a low FCGR3B copy number confers a risk of SLE but not RA.
24097207 Vitamin D in "early" primary Sjögren's syndrome: does it play a role in influencing disea 2014 Aug Beyond its well-established role in the maintenance of mineral homeostasis, 25-OH-vitamin D deficiency seems to be involved in the development and severity of several autoimmune diseases. To date, contrasting data have been reported regarding the presence of hypovitaminosis D in primary Sjögren's syndrome (pSS). To assess the prevalence of hypovitaminosis D in pSS at an early stage of the disease and to evaluate its impact on pSS clinical manifestations and disease activity, unselected consecutive subjects with recent onset dry mouth and/or dry eyes who underwent a comprehensive diagnostic algorithm for pSS (AECG criteria) were prospectively included in the study. The levels of 25[OH]-D3 were measured by monoclonal antibody immunoradiometric assay. Conditions of 25[OH]-D3 severe deficiency, deficiency, and insufficiency were defined as levels <10, <20, and 20-30 ng/ml, respectively, and their frequencies were investigated in pSS patients and controls. The levels of 25[OH]-D3 were also correlated with patients' demographic, clinical, and serologic features. Seventy-six consecutive females were included: 30/76 patients fulfilled the AECG criteria for pSS. The remaining 46/76 patients represented the control group. No statistical differences were found in the serum levels of 25[OH]-D3 between pSS patients [median levels = 20 ng/ml (IQR 9.3-26)] and controls [median levels = 22.5 ng/ml (IQR 15.6-33)]. In particular, the frequency of 25[OH]-D3 severe deficiency was not significantly different in patients with pSS when compared to controls (23 vs. 17.4 %, p value = 0.24). We found a significant correlation between serum 25[OH]-D3 levels and white blood cells count (r = 0.29, p = 0.01). More specifically, leukocytopenia was significantly associated with 25[OH]-D3 severe deficiency, being documented in 40 % of the subjects with a 25[OH]-D3 severe deficiency and in 11 % of the subjects without a severe vitamin D deficiency (p = 0.02). We did not observe any further association or correlation between hypovitaminosis D and pSS glandular and extra-glandular features. Although the role of hypovitaminosis D in pSS pathogenesis remains controversial, the results of this study encourage the assessment of vitamin D in specific pSS subsets that could mostly benefit from a supplementation.
23975134 Effect of Chinese herbal medicine for nourishing yin, supplementing qi, and activating blo 2013 Sep OBJECTIVE: To observe the effect of Chinese herbal medicine for nourishing yin, supplementing qi, and activating blood on the expression of interferon-γ (IFN-γ)/interleukin-4 (IL-4) in peripheral blood and disease activity in primary Sjogren's syndrome (pSS) patients, and to study the relationship between the immune balance of Th1/Th2 and the disease activity. METHODS: A total of 66 pSS patients were randomized with tossing coins method into two groups: the integrative therapy group (34 cases) and the control group (32 cases); and 28 healthy subjects were taken as the normal group. The integrative therapy group was treated by Chinese herbal medicines for nourishing yin, supplementing qi, and activating blood combined with hydroxychloroquine sulfate tablets and the control group was treated with hydroxychloroquine sulfate tablets. The treatment course was 3 months for both groups. The levels of serum immunoglobulin G (IgG), erythrocyte sedimentation rate (ESR), IFN-γ and IL-4 in peripheral blood were measured before and after treatment. RESULTS: Compared with the normal group, the levels of IgG, ESR, IFN-γ and IL-4 were significantly increased in pSS patients (P<0.05). Remarkably, after 3 months of treatment, these levels were dramatically decreased in both the integrative therapy group and the control group, although still higher than the normal group. The levels of IgG, ESR, IFN-γ and IL-4 in the integrative therapy group were lower than the control group and the same group before treatment (P<0.05). The ratio of IFN-γ/IL-4 also significantly decreased after treatment. Moreover, the level of IFN-γ and the ratio of IFN-γ/IL-4 in the integrative therapy group were significantly lower than the control group (P<0.05). For all patients the ratio of IFN-γ/IL-4 before and after treatment was positive correlated with the levels of IgG and ESR. CONCLUSION: Chinese herbal medicine for nourishing yin, supplementing qi, and activating blood can alleviate the disease activity of pSS by regulating the immune balance of Th1/Th2.
23837848 Are the B cells cast with the leading part in the Sjogren's syndrome scenario? 2014 Sep The autoimmune exocrinopathy Sjögren's syndrome (SS) is characterized by mononuclear cell (MNC) infiltrates of exocrine glands and overactivity of B lymphocytes. Although T cells have long been perceived as the prime effectors, increasing evidence indicates that the key role is rather served by B cells. Among related abnormalities are rheumatoid factor (RF), anti-SSA/Ro, and anti-SSB/La antibodies (Ab). Also, supporting this view is our finding of an increase in the number of circulating naïve mature B (Bm) cells, with a reciprocal decrease in that of memory B cells. Furthermore, a ratio of Bm2-plus-Bm2' cells to early Bm5-plus-late Bm5 above 5 is diagnostic. This variation partly reflects the migration of active memory B cells into the exocrine glands of the patients, as well as into their skin. More recently, the B-cell-activating factor of the TNF family (BAFF) has been endorsed with a pivotal role in B-cell survival and hence implicated in the pathogenesis of autoimmunity. In practice, B cells have turned quite attractive as a target for biotherapy. For example, treatment with anti-CD20 Ab has afforded some benefits in this disease, while BAFF blockers are still on the way, but should expand our armamentarium for treating SS. With such B-cell-directed biotherapies in mind, we delineate herein the distinguishing traits of B lymphocytes in SS.
25222653 Incident cases of primary Sjögren's syndrome during a 5-year period in Stockholm County: 2015 OBJECTIVES: To define the incidence rate of primary Sjögren's syndrome (pSS) and the prevalence of extraglandular manifestations (EGMs) at the time of diagnosis of pSS in a prospective, population-based manner. METHOD: This study included all consecutive patients referred to the Department of Rheumatology at Karolinska University Hospital for the investigation of incident pSS from 1 January 2007 to 31 December 2011. Investigation was according to the current criteria for pSS, and examination with a focus on the presence of EGMs was performed. RESULTS: Of the referred individuals, 199 out of 781 were diagnosed with pSS. We found an annual incidence rate of pSS in the Karolinska University Hospital catchment area of 3.1 [95% confidence interval (CI) 2.3-4.3] cases per 100 000 adult inhabitants. The female/male ratio of incident cases was 14/1 [frequency (female) = 0.93, 95% CI 0.89-0.96]. In our cohort, we noted lower figures for severe EGMs such as lung and neurological involvement than previously reported for prevalent pSS. The frequency of autoantibodies including antinuclear antibodies (ANA), anti-Ro/SSA, and anti-La/SSB was also lower compared to other cohorts. In our study, autoantibody-positive patients had cytopaenia significantly more often, and in patients older than 60 years primary biliary cirrhosis (PBC) was more common. CONCLUSIONS: The incidence rate of pSS is 3.1 (95% CI 2.3-4.3) per 100 000 person-years. The prevalence of autoantibodies may be lower than previously reported, and at diagnosis, patients with pSS have few severe EGMs.
25128511 MicroRNA profiling in Chinese patients with primary Sjögren syndrome reveals elevated miR 2014 Nov OBJECTIVE: Characterized by chronic inflammation, dysfunction of exocrine glands, and systemic autoimmunity, primary Sjögren syndrome (pSS) is a common autoimmune disease in elderly women. Our study was performed to explore the potential involvement of microRNA (miRNA) in Chinese patients with pSS. METHODS: Using microarrays, miRNA expression in peripheral blood mononuclear cells (PBMC) was profiled in 4 female patients with pSS and 3 healthy participants, followed by a large-scale study of 33 patients and 10 healthy individuals. Compared to the healthy participants, 202 miRNA were upregulated and 180 were downregulated in the patients with pSS. To confirm this finding, a set of regulated miRNA was further examined in a large patient group, using quantitative reverse transcriptase-PCR assays. RESULTS: MiR-181a was the miRNA that most profoundly differed between patients with pSS and healthy individuals; however, similar miRNA-181a expression profiles were found in groups with different disease phenotypes. Together, these observations suggested that an elevated miRNA-181a level is a general phenomenon in Chinese patients with pSS. CONCLUSION: In addition to the elevated miR-181a levels, our study led to the speculation that elevated miR-181a levels in the PBMC of these patients compromise the maturation of B cells, enabling them to recognize and attack autoantigens and resulting in disease phenotypes. In addition to the regulation of human miRNA, many virus-derived miRNA were unexpectedly upregulated in the patients with pSS, suggesting that viral infection of PBMC plays a role in this disease.
24343449 Quantification of conjunctival TNF-α in aqueous-deficient dry eye. 2014 Feb PURPOSE: This study aimed to quantify and compare conjunctival epithelial tumor necrosis factor (NF) α mRNA expression in Sjögren syndrome (SS), non-Sjögren syndrome aqueous-deficient dry eye (non-SS DE), and non-dry eye (NDE) control subjects. METHODS: A total of 76 subjects were recruited for this study: 25 SS (confirmed via American-European Consensus Criteria 2002), 25 non-SS DE (confirmed by symptoms and Schirmer scores ≤ 10 mm), and 26 NDE. Superior and temporal bulbar conjunctival epithelial cells were collected via impression cytology. Epithelial RNA was extracted, and TNF-α mRNA expression was quantified by real-time quantitative polymerase chain reaction. RESULTS: The expression of TNF-α mRNA was found to be significantly higher in the SS group (2.48 ± 1.79) compared to both non-SS DE (0.95 ± 1.18; p < 0.05) and NDE (0.84 ± 0.51; p < 0.05) groups. No difference in TNF-α mRNA expression was found between the non-SS DE and NDE groups (p = 0.67). CONCLUSIONS: These results demonstrate that SS-associated aqueous-deficient dry eye is associated with a significant upregulation of conjunctival epithelial TNF-α mRNA relative to both non-SS DE and control groups. The degree to which TNF-α mRNA is upregulated in SS may contribute to the severe ocular surface damage observed in these patients.
23402779 Amyloid-associated cystic lung disease in primary Sjögren's syndrome. 2013 Apr BACKGROUND: Cystic lung disease can be seen in patients with Sjögren's syndrome (SS) and is generally thought to be due to lymphocytic interstitial pneumonia. METHODS: Using computer-assisted search we identified patients with primary SS seen at Mayo Clinic, Rochester, MN during a 14-year period from 1997 to 2010 who were diagnosed with pulmonary amyloidosis confirmed on lung biopsy. Clinical records, imaging studies, and pathologic specimens were reviewed to delineate presenting features, diagnostic evaluation, and clinical course. RESULTS: Eight patients (7 women, 1 man) with primary SS were diagnosed with pulmonary amyloidosis by lung biopsy (7 surgical, 1 bronchoscopic). Their median age was 55 years (range, 32-75 years) and all were nonsmokers. Presenting symptoms included dyspnea and cough but 4 patients presented with radiologic abnormalities in the absence of respiratory symptoms. CT findings included cystic lesions and nodular opacities in all eight patients. PET scan performed in six patients did not reveal (18)F-2-deoxyglucose (FDG) uptake except in one nodule with borderline uptake. Lung biopsy demonstrated the presence of amyloid in all patients and was associated with mucosa-associated lymphoid tissue (MALT) lymphoma in three patients. Pulmonary function results were normal in five patients and revealed mild impairment in a mixed pattern in one patient. CONCLUSIONS: We conclude cystic and nodular lung lesions seen in patients with primary SS can represent amyloidosis which can be associated with MALT lymphoma in some of these patients.
25022358 Update on infections and vaccinations in systemic lupus erythematosus and Sjögren's syndr 2014 Sep PURPOSE OF REVIEW: To provide an update on infections in systemic lupus erythematosus (SLE) and Sjögren's syndrome, particularly addressing their role as triggers of autoimmunity, their impact on mortality, the main microorganisms, the approaches to differential diagnosis with disease flares and recommendations for vaccination. RECENT FINDINGS: New mechanisms for autoimmunity triggered by Epstein-Barr virus and human commensal microbiota have been described. The increased risk for tuberculosis was recently demonstrated for the first time in Sjögren's syndrome. C-reactive protein was reported to be a more sensitive and specific marker for bacterial infections in SLE than procalcitonin and phagocyte-specific S100A8/A9 protein. Inactivated vaccines are well tolerated and efficacy was demonstrated for influenza vaccine. Immunogenicity is generally reduced but adequate in SLE. Prednisone or immunosuppressants are associated with decreased vaccine serological response, whereas hydroxicloroquine seems to improve vaccine immunogenicity. Other infection-preventive measures for these diseases include antimalarials and prophylaxis for tuberculosis or Pneumocystis jirovecii. SUMMARY: Advances in the role of infectious agents as triggers for SLE and Sjögren's syndrome have provided new insights into disease development. Knowledge on vaccine immunogenicity, safety and efficacy has improved with evidence of a generally reduced but adequate response for inactivated vaccines in SLE. Other preventive measures comprise infection prophylaxis and antimalarials.