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ID PMID Title PublicationDate abstract
24875508 Sauvé-Kapandji procedure in a patient with wrist disarticulation: case report. 2014 The advantage of preserving the distal radioulnar joint in wrist disarticulation is that full forearm rotation is possible if the joint is intact, which improves the capability of the amputee. The Sauvé-Kapandji procedure has been performed to treat rheumatoid or post-traumatic chronic instability and/or arthritis of the distal radioulnar joint. We report a patient with wrist disarticulation that presented to us with limited supination of the wrist due to an injured distal radioulnar joint. We performed the Sauvé-Kapandji procedure, and the patient could regain functional supination of the forearm without losing the ulnar styloid flare that improved prosthetic suspension. This case suggests that the Sauvé-Kapandji procedure can be performed to maintain the advantage of wrist disarticulation even when the initial trauma involves an irreparable injury of the distal radioulnar joint.
24373735 Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxid 2014 Jan 15 We report herein the development, synthesis, physicochemical and pharmacological characterization of a novel class of pharmacodynamic hybrids that selectively inhibit cyclooxygenase-2 (COX-2) isoform and present suitable nitric oxide releasing properties. The replacement of the ester moiety with the amide group gave access to in vivo more stable and active derivatives that highlighted outstanding pharmacological properties. In particular, the glycine derivative proved to be extremely active in suppressing hyperalgesia and edema.
23639406 Elevated specific peripheral cytokines found in major depressive disorder patients with ch 2013 Oct Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression.
24718892 Hodgkin lymphoma after autoimmune diseases by age at diagnosis and histological subtype. 2014 Jul BACKGROUND: Increased risk of Hodgkin lymphoma (HL) associated with personal history of several autoimmune diseases (ADs), such as rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and immune thrombocytopenic purpura, are known. Whether there are other HL-related ADs and whether the increased risk of HL after ADs holds across sex, age, year of diagnosis, or HL histological subtype is unclear. PATIENTS AND METHODS: We systematically analyzed the risk of HL in 878 161 Swedish patients diagnosed with 33 different ADs in 1964-2010. During ∼10-year follow-up of ADs patients, 371 incident HL cases were diagnosed. RESULTS: Significantly increased overall standardized incidence ratio (SIR) for HL after ADs was 2.0 (95% confidence interval: 1.8-2.2); AD-specific SIRs: autoimmune hemolytic anemia 19.9 (7.2-43.6), sarcoidosis 10.3 (7.8-13.4), systemic lupus erythematosus 8.4 (5.2-12.9), immune thrombocytopenic purpura 7.0 (3.2-13.3), polyarteritis nodosa 6.6 (1.2-19.5), polymyositis/dermatomyositis 6.3 (2.0-14.9), Behcet's disease 5.6 (2.7-10.3), Sjögren's syndrome 5.0 (2.1-9.8), rheumatoid arthritis 3.2 (2.6-3.9), polymyalgia rheumatica 2.2 (1.4-3.5), and psoriasis 1.9 (1.3-2.6). Men with AD had slightly higher risk of HL (2.4, 2.0-2.7) compared with women (1.8, 1.5-2.0). Only 23% of ADs were diagnosed before age 35 years and the overall SIR for HL diagnosis before age 35 [1.4, (1.0-1.8)] was lower than that in older ages [35 ≤ age < 50: 2.1 (1.6-2.7); age ≥ 50: 2.2 (2.0-2.5)], except for sarcoidosis [age < 35: 19.3 (10.5-32.5); 35 ≤ age < 50: 10.4 (5.7-17.5); age ≥ 50: 8.4 (5.6-12.1)]. Risks of all classical HLs significantly increased after ADs: lymphocyte depletion 3.7 (1.5-7.6), lymphocyte-rich 3.7 (2.3-5.9), mixed cellularity 2.4 (1.8-3.2), and nodular sclerosis 1.7 (1.3-2.1). CONCLUSION: Several, but not all ADs (11/33), had a positive association with all classical histological subtypes of HL. Higher risks of classical HL after polyarteritis nodosa, polymyositis/dermatomyositis, Behcet's disease, Sjögren's syndrome, polymyalgia rheumatica, and psoriasis were novel findings of this study.
23792059 Autoimmune associations and autoantibody screening show focused recognition in patient sub 2013 Sep Autoimmune associations in myasthenia gravis (MG)-patients and their relatives have not been re-assessed since their separation into early- or late-onset MG (EOMG, LOMG), or thymoma-associated MG. Here, we analysed 226 EOMG-, 97 LOMG-, and 150 thymoma-patients for autoimmune disorders in themselves and their relatives. From 283 of them sera were tested for different organ- and non-organ-specific autoantibodies (autoAbs) by immunofluorescence test (IFT) and ELISA; genotyping was performed in 213 patients. Relatives with autoimmune disorders were reported by more patients with EOMG (40% of 210) than LOMG (20% of 89; p < 0.01) than thymomas (8% of 150; p < 0.001). In 150 genotyped EOMG-females, the known risk allele of the immuno-regulatory PTPN2 2 (R620W) appeared commoner in those with second autoimmune diseases (p ∼ 0.06), or with autoimmune relatives (p ∼ 0.03), than in those without. Organ-specific autoAbs were found in ∼ 30% of all MG-patients, autoAbs to striated muscle only in patients with thymoma-MG (62%) or LOMG (61%). Titers against adrenal cortex were lower in LOMG-patients. Disease-associated autoAbs against systemic targets or 'natural autoAbs' - except of autoAbs to nuclei - were uncommon in all groups (< 13%). Thus-with rare exceptions in EOMG and LOMG-we found minimal support for the notion that autoimmune patients have wide-ranging autoreactivity that causes disease only if it targets such Achilles' heels as the muscle acetylcholine receptor; even in thymoma-patients the autoAbs are sharply focused on a restricted range of muscle, cytokine and endocrine targets.
25524206 Sjögren's syndrome and chemokines. 2014 Interferon (IFN)-γ-induced protein 10 (IP-10) and its receptor, chemokine (C-X-C motif) receptor (CXCR)3, appear to contribute to the pathogenesis of Sjögren's syndrome (SS). The expression of IP-10 and CXCR3 is increased, in salivary glands from SS patients, both in the ductal epithelium adjacent to lymphoid infiltrates and in lymphocytes. IFN-γ induces the production of high levels of IP-10 and monokine induced by IFN-γ (MIG) proteins from cultured SS salivary epithelial cells. Under the influence of IFN-γ, IP-10 secreted by salivary cells, recruits T helper (Th)1 lymphocytes that may be responsible for enhanced IFN-γ, which in turn stimulates a further IP-10 secretion from epithelial cells creating an amplification feedback loop and perpetuating the autoimmune process. Determination of high level of IP-10 in tears and saliva is therefore a marker of a Th1 orientated immune response. In experimental settings IP-10 antagonists can ameliorate the progression of autoimmune sialadenitis, providing a new therapeutic approach to SS. Further studies are needed to investigate whether IP-10 is a novel therapeutic target in SS in humans.
24974497 Hypokalaemic paralysis and normocalcaemic tetany--a rare presentation of Sjogren's syndrom 2013 Nov 38 year old woman was admitted with acute onset of quadriplegia. Biochemical investigation revealed severe hypokalaemia with hyperchloraemic metabolic acidosis, alkaline urine, and positive urinary anion gap which are the hallmark of distal tubular acidosis. In addition she also had hypophosphataemia, normoglycaemic glycosuria, aminoaciduria, and hyperphosphaturia suggestive of proximal tubular dysfunction. Further evaluation confirmed the diagnosis of Sjogren's syndrome. Interestingly our patient also had carpopedal spasm despite normal calcium and magnesium level. Quadriplegia and carpopedal spasm improved with correction of hypokalaemia and acidosis. Proximal tubular abnormalities (except albuminuria) were normalised at the time of discharge. Distal tubular acidosis is a well known renal manifestation of Sjogren's syndrome. But this type of transient proximal tubular dysfunction with distal tubular acidosis in Sjogren's syndrome is very rare and hypokalaemic tetany also deserves mention.
24741622 Atrioventricular conduction delay in the second trimester measured by fetal magnetocardiog 2014 INTRODUCTION: Fetal AV block in SSA/Ro pregnancies is generally not seen before 18-week gestation and onset is rare after 28-week gestation. If complete AV block appears, it is believed to be irreversible. The purpose of the study was to evaluate precise electrophysiological AV conduction from 18-week gestation onwards. PATIENTS AND METHODS: 21 fetuses of pregnant women with collagen vascular diseases were included in the study group and 59 healthy fetuses served as controls. In addition to fetal echocardiography, fetal magnetocardiography (fMCG) was used to investigate precise electrophysiological fetal cardiac time intervals (fCTIs). RESULTS: The PR segment (isoelectric segment between the end of the P wave and the start of the QRS complex) was significantly prolonged (P < 0.036 2nd trimester, P < 0.023 3rd trimester) in both trimesters within the study group. In fetuses less than 23-week gestational age, a nearly complete separation was found, where a PR segment of 60 ms or greater completely excluded control fetuses. All other fCTIs did not differ significantly. None of the fetuses progressed to a more advanced heart block. CONCLUSION: Slight antibody effects in pregnancy, leading to PR segment prolongation, can already be seen from 18-week gestation onwards by fMCG. Serial fetal Doppler echocardiography and additional fMCG can be useful methods to measure early and precise AV conduction time, to achieve best surveillance for these high-risk pregnancies.
23723980 The association between TNF-α, IL-10 gene polymorphisms and primary Sjögren's syndrome: 2013 OBJECTIVE: Previous studies have evaluated the associations of TNF-α, IL-10 gene polymorphisms and susceptibility to pSS, but the results remained controversial. To assess the associations between TNF-α-308, IL-10-1082, -819, -592 polymorphisms and pSS risk, a meta-analysis was conducted. METHOD: The available articles were searched in PubMed, EMBASE and MEDLINE. ORs with 95% CIs were calculated to determine the strength of associations by fixed-effects or random-effects models. The data about IL-10-1082, -819, -592 polymorphisms were analyzed in the additive, dominant and recessive modes. The associations between haplotypes of IL-10 gene and susceptibility to pSS were also assessed. RESULTS: A total of 9 relevant studies were identified in the meta-analyses. TNF-α-308 A allele was significantly associated with pSS (OR = 1.8, 95% CI: 1.53-2.13). The IL-10 -1082 G allele and the genotype "GCC/ATA" were identified as a candidate genetic risk factor for pSS. Under the dominant model for -819 and -582, the overall ORs suggested that individuals with genotype (CC+TC) or (CC+AC) may have a 59% increased risk of pSS in Caucasians population (OR = 1.59, 95% CI:1.09-1.23). Besides, the genotype "ATA/ATA" may be a protective factor against the development of pSS in Caucasians (OR = 0.40, 95% CI:0.19-0.84). CONCLUSION: The meta-analysis demonstrated TNF-α-308 A, IL-10-1082 G allele were significantly associated with pSS susceptibility, supporting these alleles were predisposing factors for pSS. In Caucasian population, the genotype "ATA/ATA" may be a protective factors.
23480241 Sarcoidosis and Sjögren's syndrome: clinical and salivary evaluation. 2013 Sep BACKGROUND: Sarcoidosis and Sjögren's syndrome are two different diseases; however, when affecting the salivary glands, both diseases exhibit similar clinical signs and symptoms, which often complicates the diagnosis. The purpose of this study was to investigate the possibility of using salivary electrophoresis to differentiate between the two diseases. METHODS: Saliva was collected from patients with sarcoidosis and patients with Sjögren's syndrome. Salivary flow rate, total protein, and electrophoretic profiles were examined. RESULTS: Mean salivary flow rate was 0.41 ± 0.07 ml/min/gland vs. 0.43 ± 0.07 ml/min/gland; total salivary protein was 130.0 ± 29.2 mg% vs. 104.0 ± 8.8 mg% for sarcoidosis vs. Sjögren's syndrome, respectively. No differences were observed in salivary flow rate, total salivary protein, or electrophoretic profile between patients with sarcoidosis and patients with Sjögren's syndrome (P = 0.768, 0.718, and 1.000, respectively). CONCLUSIONS: Salivary protein electrophoresis does not appear to be useful to differentiate between sarcoidosis and Sjögren's syndrome.
24093879 Temporal histological changes in lacrimal and major salivary glands in mouse models of Sjo 2013 Oct 5 BACKGROUND: Evidence in imaging studies suggests that there may be differences in glandular involvement in Sjogren's syndrome (SS) depending on the stage of the disease. No detailed histological studies are available to show if there are any such difference in glandular involvement at various time periods and stages of SS. This cross sectional study examines the inflammatory changes in mouse models of SS at various ages. METHODS: The histological changes in major salivary and lacrimal glands were studied at ages of 3, 6, 9, 12, 15 and 18 months in both sexes in well characterized mouse models of SS, non-obese diabetes mouse and Interleukin-14 alpha-transgenic mice. RESULTS: Our results indicate that early inflammation concurrently occur in submandibular and lacrimal glands around the age of 6 weeks. Parotid glands are involved much later in the course of SS with less severe inflammation. Sublingual glands are rarely involved. CONCLUSIONS: Our conclusions are that SS may be an organ specific disease with early inflammation occurring in submandibular and lacrimal glands, followed by the parotid. Non organ specific events occur in later courses of the disease. The understanding of the disease progression is important in tailoring early local therapeutic interventions before complete destruction of salivary and lacrimal glands.
24411167 Differentiation of follicular helper T cells by salivary gland epithelial cells in primary 2014 Jun Follicular helper T cells (Tfh), which play a pivotal role in B cell activation and differentiation in lymphoid structures, secrete IL-21 whose augmented secretion is a hallmark of several autoimmune diseases. To decipher the cellular and molecular interactions occurring in salivary glands of patients suffering from primary Sjögren's syndrome (pSS), we investigated whether salivary gland epithelial cells (SGECs) were capable to induce Tfh differentiation. Co-cultures of naïve CD4(+) T cells and SGECs from both patients with pSS and controls were performed. Here, we report that IL-6 and ICOSL expression by SGECs contributes to naïve CD4(+) T differentiation into Tfh cells, as evidenced by their acquisition of a specific phenotype, characterized by Bcl-6, ICOS and CXCR5 expression and IL-21 secretion, but also but by their main functional feature: the capacity to enhance B lymphocytes survival. We demonstrated an increase of serum IL-21 with systemic activity. Finally, we analyzed the potential occurrence of a genetic association between IL-21 or IL-21R gene polymorphisms and pSS or elevated IL-21 secretion. This study, which demonstrates a direct induction of Tfh differentiation by SGECs, emphasizes a yet unknown pathogenic role of SGECs and suggests that Tfh and IL-21 might be relevant biomarkers and/or therapeutic targets in primary Sjögren's syndrome.
24862599 Xerostomia. 2014 Xerostomia is the subjective feeling of oral dryness. The major causes are Sjögren's syndrome (SS), medication and radiotherapy to the head and neck. SS is a chronic systemic autoimmune disease characterized by infiltration of the exocrine glands, the salivary and lacrimal ones in particular. The pathogenesis involves systemic B cell hyperactivity and T cell lymphocytes targeting glandular epithelial cells. About 7.5% of patients with SS develop malignant B cell lymphoma, mostly mucosa-associated tissue lymphomas. Certain classes of drugs can induce hyposalivation and/or xerostomia by, e.g., targeting neurotransmitters and receptors. As a result, amongst others the production of fluid and electrolytes in salivary glands can be reduced and the salivary composition can change. During head and neck radiotherapy, the administration of high doses to the major salivary glands, which are located in the periphery of the head, leads to progressive loss of glandular function and a diminished salivary output. Reduction of the dose and the volume of irradiated salivary glands by advanced radiotherapy techniques can be highly beneficial for patients.
24569818 Salivary gland scintigraphy in Sjögren's syndrome. Comparison of the diagnostic performan 2014 Aug 6 The aim of this study was to compare the diagnostic utility of visual versus semi-quantitative analysis of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome (SS). PATIENTS, METHODS: 99mTc-pertechnetate salivary gland scintigraphy was performed in 145 patients (133 women, 12 men) with clinically suspicious SS. The images were interpreted with visual and semiquantitative methods and the diagnostic performances for SS were compared using uptake and excretory functional parameters. RESULTS: In total, 76 patients (52.4%) were finally diagnosed with SS. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of visual analysis for the diagnosis of SS were 88.2%, 48.6%, 65.1%, 79.1%, and 69.2%, respectively. Semiquantitative values, the area under the ROC curve for uptake ratio and percentage excretion in the right salivary glands were significantly greater than 0.5 (p < 0.05). However, the percentage excretion in the left salivary glands did not show a statistically significant diagnostic ability for SS. The diagnostic ability of visual assessment was greater than that of the semiquantitative method in terms of evaluating uptake and excretory function in the submandibular glands. CONCLUSION: Visual analysis of salivary gland scintigraphy showed greater diagnostic utility than semiquantitative assessment in the diagnosis of SS, especially in the submandibular glands.
24322322 [Thymic mucosa-associated lymphoid tissue (MALT) lymphoma developing during long-term foll 2013 Nov Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of lymphoma that arises in small CD20-positive lymphocytes. We encountered a case of thymic MALT lymphoma treated with surgical intervention during long-term follow-up for Sjögren's syndrome and idiopathic thrombocytopenic purpura (ITP). Although symptomatic remission of Sjögren's syndrome and ITP had already been achieved, the levels of anti-SSA and anti-SSB antibodies remained high. Chronic stimulation by these antibodies may contribute to the development of MALT lymphoma. A careful follow-up may be indicated for this case with a complex immunological background.
24269434 [Non-infectious corneal macroperforations treated with a combination of Tachosil(®) and T 2014 Jun CLINICAL CASE: We report 2 cases of patients affected by non-infectious corneal macroperforations treated with TachoSil(®) and Tutopach(®), which closed the defect. DISCUSSION: This procedure is an excellent choice for the emergency treatment of corneal perforation, especially in those centres that have no other therapeutic options, preserving the eye and visual acuity.
24065634 The circadian clock in oral health and diseases. 2014 Jan Most physiological processes in mammals display circadian rhythms that are driven by the endogenous circadian clock. This clock is comprised of a central component located in the hypothalamic suprachiasmatic nucleus and subordinate clocks in peripheral tissues. Circadian rhythms sustain 24-hour oscillations of a large number of master genes controlling the correct timing and synchronization of diverse physiological and metabolic processes within our bodies. This complex regulatory network provides an important communication link between our brain and several peripheral organs and tissues. At the molecular level, circadian oscillations of gene expression are regulated by a family of transcription factors called "clock genes". Dysregulation of clock gene expression results in diverse human pathological conditions, including autoimmune diseases and cancer. There is increasing evidence that the circadian clock affects tooth development, salivary gland and oral epithelium homeostasis, and saliva production. This review summarizes current knowledge of the roles of clock genes in the formation and maintenance of oral tissues, and discusses potential links between "oral clocks" and diseases such as head and neck cancer and Sjögren's syndrome.
23497939 Sjögren's syndrome and the epithelial target: a comprehensive review. 2013 May The most difficult component in our understanding of human autoimmunity remains a rigorous dissection of etiological events. Indeed, the vast literature on autoimmune diseases focuses on the inflammatory response, with the hope of developing drugs that reduce inflammation. However, there is increasing recognition that understanding the immunobiology of target tissues will also have direct relevance to disease natural history, including breach of tolerance. Sjögren's syndrome is essentially an epitheliitis and there are major changes to normal architectural salivary organization. We propose that loss of homeostasis is the initial event that precipitates inflammation and that such inflammatory response includes not only the adaptive response, but also an intense innate immune/bystander response. To understand these events this review focuses on the architecture, phenotype, function and epithelial cell organization. We further submit that there are several critical issues that must be defined to fully understand epithelial cell immunobiology in Sjögren's syndrome, including defining epithelial cell polarity, cell-cell and cell to extracellular matrix interactions and a variety of chemical and mechanical signals. We also argue that disruption of tight junctions induces disorganization of the apical pole of salivary acinar cells in Sjögren's syndrome. In addition, there will be a critical role of inflammatory cytokines in the apico-basal relocation of tight junction proteins. Further, the altered disorganization and relocation of proteins that participate in secretory granule formation are also dysregulated in Sjögren's syndrome and will contribute to abnormalities of mucins within the extracellular matrix. Our ability to understand Sjögren's syndrome and develop viable therapeutic options will depend on defining these events of epithelial cell biology.
24998369 Features of usual interstitial pneumonia in patients with primary Sjögren׳s syndrome com 2014 Jul BACKGROUND: The different characteristics of usual interstitial pneumonia in patients with primary Sjögren׳s syndrome (UIP/pSS) compared with idiopathic pulmonary fibrosis (UIP/IPF) are not fully understood. This study aimed to compare characteristics, prognosis, and treatment responses in these patients. METHODS: Among 129 consecutive patients who underwent surgical lung biopsy to diagnose diffuse lung diseases at Kanagawa Cardiovascular and Respiratory Center between 1998 and 2002, we identified 10 and 19 patients with UIP/pSS and UIP/IPF, respectively. Baseline characteristics, chest high-resolution computed tomography (HRCT) and pathological findings, and the clinical course were compared between the two groups. Responses to immunosuppressive therapy were analyzed by comparing pulmonary function and clinical status before and one year after treatment initiation. RESULTS: More patients in the UIP/pSS group tended to be female and older than those in the UIP/IPF group (mean age, 68 years vs. 62 years). In addition, they more commonly exhibited enlarged mediastinal lymph nodes and bronchial wall thickening on HRCT. Pathologically, in the UIP/pSS group, interstitial inflammation, plasma cell infiltration, lymphoid follicles with germinal centers, cysts, bronchiolitis, and pleuritis were significantly more prominent, whereas smooth muscle hyperplasia and fibroblastic foci were milder (all P<0.05). The prognosis was better for UIP/pSS compared with UIP/IPF patients (P=0.01). In addition, immunosuppressive therapy provided better disease control for those with UIP/pSS (83%, 5/6) compared UIP/IPF (7%, 1/15). CONCLUSION: This study identified distinct clinical, radiological, and pathological characteristics of UIP/pSS compared with UIP/IPF. Immunosuppressive treatment could be a therapeutic option for UIP/pSS.
23351335 IgG4-related disease: why high IgG4 and fibrosis? 2013 Jan 25 The hallmarks of IgG4-related disease (IgG4-RD) are lymphoplasmacytic tissue infiltration with a predominance of IgG4-positive plasma cells, accompanied by fibrosis, obliterative phlebitis, dacryoadenitis, and elevated levels of IgG4. In a recent issue of Arthritis Research & Therapy, Tsuboi and colleagues demonstrated that regulatory T (Treg) cell-and T helper 2 (Th2) cell-derived cytokines contribute to the pathogenesis of Mikulicz's disease, an activation pathway that appears to be common for IgG4-RD. Additional organ-specific factors may account for the different organ involvement of IgG4-RD.