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ID PMID Title PublicationDate abstract
20544243 Acrylamine-induced autoimmune phenomena. 2010 Sep The objective of this study is to document a series of cases of occupationally derived autoimmune disease. Individuals with occupational exposure to acrylamides were evaluated clinically and biochemically/immunologically for evidence of autoimmune disease. Symptoms and signs and immuno-reactivity were monitored during exposure-free and re-exposure as part of the individuals' clinical evaluation. Six individuals with occupational acrylamide exposure had clinical and laboratory alterations characteristic of drug-induced autoimmune disease, specifically lupus, anti-phospholipid syndrome, Sjogren's syndrome, scleroderma, and polymyositis. The similarity of the full spectrum of disease in the reported patients to that found with procainamide strongly suggests the effects of occupational exposure. This uncontrolled study suggests the need for a full epidemiologic analysis of all individuals working with such occupational exposure, including full clinical and immunological examination.
20714326 An essential role for mast cells as modulators of neutrophils influx in collagen-induced a 2011 Jan Mast cells are involved in immune disorders so that many of the proinflammatory and tissue destructive mediators produced by these cells have been implicated in the pathogenesis of rheumatoid arthritis. This scenario prompted us to investigate the correlation between mast cell degranulation and neutrophil influx within the digits and knees joints of arthritic mice assessing what could be the functional role(s) of joint mast cells in the response to collagen immunization. DBA/1J mice were submitted to collagen-induced arthritis and disease was assessed on day 21, 32 and 42 post-immunization. Pharmacological treatment with the glucocorticoid prednisolone, commonly used in the clinic, and nedocromil, a mast cell stabilizer, was performed from day 21 to 30. Arthritis develop after immunization, gradually increased up to day 42. Neutrophil infiltration peaked on day 32 and 21, in the digits and knees, respectively, showing an unequal pattern of recruitment between these tissues. This difference emerged for mast cells: they peaked in the digits on day 21, but a higher degree of degranulation could be measured in the knee joints. Uneven modulation of arthritis occurred after treatment of mice with prednisolone or nedocromil. Neutrophils migration to the tissue was reduced after both therapies, but only prednisolone augmented mast cell migration to the joints. Nedocromil exerted inhibitory properties both on mast cell proliferation and migration, more effectively on the digit joints. Thus, collagen induced an inflammatory process characterized by tissue mast cells activation and degranulation, suggesting a potential driving force in propagating inflammatory circuits yielding recruitment of neutrophils. However, the different degree of affected joint involvement suggests a time-related implication of digits and knees during collagen-induced arthritis development. These results provide evidence for local alterations whereby mast cells contribute to the initiation of inflammatory arthritis and may be targeted in intervention strategies.
20003498 Separating therapeutic efficacy from glucocorticoid side-effects in rodent arthritis using 2009 INTRODUCTION: Glucocorticoids have extensively been used in the treatment of rheumatoid arthritis and other inflammatory diseases. However, their side-effects remain the major limitation in clinical use and an improved therapeutic index is needed. METHODS: Therapeutic efficacy and persistence of free and liposomal dexamethasone phosphate (DXM-P) were determined in mouse collagen-induced arthritis. For regimens with equal therapeutic benefit, the side-effect profiles were analysed over time with respect to collagen breakdown, suppression of the hypothalamus-pituitary-adrenal (HPA) axis, changes in blood glucose levels and the haematological profile. In addition, the presence of drug was monitored in plasma. RESULTS: Liposomal DXM-P, but not free drug, resulted in a persistent anti-inflammatory effect. Comparable clinical benefit was achieved with a single administration of 4 mg/kg liposomal DXM-P or daily administrations of 1.6 mg/kg free drug for at least 7 days. For the liposomal form, but not for the free form, we observed a limitation of the suppression of the HPA axis in time and an absence of the drug-induced gluconeogenesis. CONCLUSIONS: Liposomal DXM-P, but not free DXM-P, achieves therapeutic persistence in mouse collagen-induced arthritis, which results in drug-free periods of therapeutic benefit. The physical absence of drug after day 2 is associated with a reduction of the typical glucocorticoid side-effects profile. Liposomal DXM-P thereby has an improved therapeutic window.
21035924 [Hypokalemia induced quadriparesis as the presenting manifestation of Gougerot-Sjögren's 2011 Oct We report a 30-year-old woman who presented with a hypokaliemia-related subacute quadriparesis. The various causes of hypokalemia induced paresis were discussed but the association of hypokalemia with metabolic acidosis and normal anion gap was diagnostic of distal renal tubular acidosis. The renal tubulopathy was the presenting manifestation of a primary Sjogren's syndrome. Distal renal tubular acidosis concerns a third of the patients affected by this auto-immune disease.
21078725 Activation of the interferon pathway in peripheral blood of patients with Sjogren's syndro 2011 Feb OBJECTIVE: DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR) were performed to identify key target genes in peripheral blood from patients with Sjögren's syndrome (SS). METHODS: DNA microarray analysis was performed in 19 patients with SS (all women) and 10 healthy controls (5 men and 5 women) using a low-density DNA microarray system with 778 genes. For confirmation, the expression of upregulated genes was analyzed by quantitative real-time PCR in another 37 SS patients (35 women and 2 men) and 9 healthy controls (8 women and 1 man). Relationships between gene signatures and various clinical measures, such as disease duration, symptoms and signs, complications, immunological findings, and salivary and lacrimal functions, were analyzed. RESULTS: Interferon-α (IFN-α)-inducible protein 27 (IFI27) showed the most significant difference between SS patients and controls in the microarray screening. We performed quantitative RT-PCR for IFI27. IFI27 gene expression level was increased in patients with SS compared with controls (p < 0.01) by real-time PCR, supporting our observations from the microarray data. The level of IFI27 was significantly correlated with serum IgG levels (r = 0.462, p < 0.01) and ß(2)-microglobulin (r = 0.385, p < 0.05), soluble interleukin 2 receptor (r = 0.473, p < 0.01), erythrocyte sedimentation rate (r = 0.333, p < 0.05), and antinuclear antibody titer (speckled pattern; r = 0.445, p < 0.01). CONCLUSION: Our results suggest that upregulation of IFN-inducible genes in SS patients is a systemic phenomenon, and IFN may play an important role in the pathogenesis of SS. The expression level of IFI27 could be an effective and specific biomarker associated with SS.
20732442 Bone marrow cells are a source of undifferentiated cells to prevent Sjögren's syndrome an 2010 Nov Non-obese diabetic (NOD) mice develop Sjögren's-like syndrome (Ss) and a gradual loss of saliva secretory function. Our previous study showed that injections of matched normal spleen cells with Complete Freund's Adjuvant (CFA) reversed salivary gland dysfunction in 14-week-old NOD mice, which had established Ss. The spleen and bone marrow are closely related organs, and both are among the first sites of hematopoiesis during gestation. Noticing a rapidly increasing number of clinical trials using bone marrow (BM) cells treatments for autoimmune diseases, we tested if BM cells can prevent Ss and restore salivary glands' function. We injected CFA and MHC class I-matched normal BM cells in 7-week-old NOD mice, which had not yet developed Ss. We found at week 52 post-treatment that all NOD mice receiving BM cells and CFA had a recovery of salivary flow and were protected from Ss and diabetes. BM cells-treated mice had their salivary function restored quantitatively and qualitatively. Saliva flow was higher (p<0.05) in BM cells-transplanted mice when compared to control mice, which continued to deteriorate over time. Total proteins, epidermal growth factor, amylase, and electrolytes concentrations in saliva of BM cells-treated mice were not significantly changed at week 44 and 52 post-therapy when compared to pre-therapy (when the mice did not have Ss). Restoration of salivary flow could have resulted from a combination of rescue and paracrine effects from BM cells. This study suggests that a combined immuno- and cell-based therapy can permanently prevent Ss and restored salivary function in NOD mice.
20502032 Diagnostic markers of Sjögren's syndrome. 2010 Establishing a diagnosis of Sjögren's syndrome (SS) has been difficult without sensitive laboratory markers, and in light of the non-specificity of the symptoms of dry eyes and mouth. Rather than complaints about dry eyes or dry mouth, objective symptoms and extraglandular manifestations should raise suspicion of SS. This evaluation requires the detection of antibodies against Ro (SSA) and La (SSB) or a pathologic salivary gland biopsy. Since an invasive biopsy is not always performed, further diagnostic markers are required. Recently antibodies against alpha-fodrin have been shown to be present in the majority of untreated patients, and can be used in the screening process of SS as an additional marker.
20334476 Pancreatic function and morphology in Sjögren's syndrome. 2010 Jun OBJECTIVE: Sjögren's syndrome (SS) is considered to be a universal exocrinopathy most likely based on autoimmune mechanisms. The degree of exocrine involvement in SS with the exception of salivary and lachrymal glands is, however, not yet established. MATERIAL AND METHODS: We therefore examined the morphology, the exocrine and endocrine functions of the pancreas in 12 healthy consecutively included levolunteers with established SS, but without known pancreatic disease, using secretin-stimulated magnetic resonance cholangiopancreatography (MRCP), a Lundh test, oral glucose tolerance test, and blood sampling. RESULTS: Twenty-five percent of the patients had morphological changes of pancreas as evaluated by secretin-stimulated MRCP, and two patients had chronic pancreatitis-like changes. Four patients had reduced exocrine function of the pancreas with either significantly reduced amylase and/or lipase in the pancreatic juice. CONCLUSIONS: The prevalence of pancreatic dysfunction was increased to 25-33% in the study population which is much higher than in the background population. Thus, pancreatic dysfunction and chronic pancreatitis should be considered in SS.
19519622 Cytokines in Sjögren's syndrome. 2009 Nov Cytokines play a central role in the regulation of immunity and are often found to be deregulated in autoimmune diseases. Sjögren's syndrome is a chronic autoimmune disease characterized by inflammation and loss of secretory function of the salivary and lachrymal glands. This review highlights the current knowledge of the expression and the function of pro- and anti-inflammatory cytokines both locally and systemically in Sjögren's syndrome patients. In the salivary glands, saliva and serum of these patients, many pro-inflammatory cytokines are upregulated. Concomitantly, most anti-inflammatory cytokines are not detectable or are expressed at low levels. Besides a role in inflammation, cytokines are also thought to be involved in salivary gland dysfunction by directly interfering with the epithelial cells in the glands. Future research on the role of novel cytokines in Sjögren's syndrome in combination with a better understanding of the effect of cytokines on exocrine dysfunction will aide the identification of the best therapeutic targets for Sjögren's syndrome.
19373541 Pulmonary and thymic lymphoid hyperplasia in primary Sjögren's syndrome. 2009 Feb Pulmonary and thymic lymphoid hyperplasia with characteristic clinicoradiological manifestations were seen in a 71-year-old woman who was diagnosed with primary Sjögren's syndrome. A hazy opacity 12 mm in diameter and an anterior mediastinal nodule 20 mm in diameter were incidentally detected on computed tomography. Thoracoscopic biopsy revealed lymphoid hyperplasia in the lung accompanying thymic lymphoid hyperplasia. Immunohistochemically, the pulmonary lesion was considered to be nodular lymphoid hyperplasia (NLH), not lymphoma. A previously undescribed finding in the NLH was the hazy opacity containing an air bronchiologram, not a solid nodule. This finding might suggest a common causal relation for NLH, thymic hyperplasia, and primary Sjögren's syndrome.
20444857 Assessment of patients with primary Sjögren's syndrome--outcome over 10 years using the S 2010 Aug OBJECTIVE: To evaluate the long-term outcome in a cohort of patients with primary SS (PSS) using the recently proposed Sjogren's Syndrome Damage Index. METHODS: We reviewed the clinical records of 60 patients attending our Sjögren's clinic at University College London Hospital, who strictly fulfilled the American-European Consensus Group criteria and on whom we had a minimum of 10 years of follow-up (or until death) during this decade. However, we could not retrospectively identify damage in the oral domain as this had not been recorded reliably. RESULTS: Fifty-five per cent of patients in this study had no damage after 10 years of disease--a lower figure than our comparative group of patients with SLE (32.4%). Damage accrual was mostly in the ocular domain, parotid swelling and malignancy categories. There was a 6-fold increase in the 'malignancy damage' compared with the 2-fold increase in the total damage score in PSS. CONCLUSIONS: Unlike patients with SLE, it is clear that fewer patients with SS develop permanent damage, even after 10 years of follow-up. These data are thus encouraging but clearly larger numbers of patients need to be assessed.
20174847 Clinical analysis of primary Sjögren's syndrome complicating anemia. 2010 May This is a cross-sectional study to assess the prevalence and causes of anemia in the primary Sjögren's syndrome (pSS). One hundred and thirty-two consecutive patients with pSS were enrolled into the study. Standard hematological and immunological tests and examination of bone marrow were performed. Anemia occurred in 45 (34.1%) patients. The causes of anemia included anemia of chronic disease (69%), autoimmune hemolytic anemia (AIHA, 18%), iron deficiency anemia (9%) and other causes (4%), of which AIHA caused the most severe anemia. The prevalence of ANA, anti-Ro/SSA, and anti-La/SSB was much higher in patients with anemia than those without anemia. Anticardiolipin antibodies were most commonly detected in AIHA; the prevalence of IgG and hypocomplementemia in AIHA was much higher in patients without anemia. Abnormal bone marrow changes were observed in two cases with anemia, one with morphological changes in the myeloid, megakaryocytic, and erythroid lineages and one with hypocellularity in the erythroid lineage. Therefore, pSS patients with anemia may be associated with destruction of peripheral mature blood cells, impaired red cells production, and hematopoietic abnormalities due to an immune mechanism, although the concrete pathogenesis is still unclear.
20928912 Multifactorial causes of irritating bladder symptoms in patients with Sjögren's syndrome. 2011 Jan AIMS Patients with Sjögren's syndrome (SS) are reported to have an increased severity of irritating bladder symptoms, including urinary frequency and urgency. The mechanism remains unclear. The aim of this study is to elucidate the possible etiologies underlying this problem. METHODS: Data from 23 female patients with SS (15 primary and 8 secondary) who were treated in the urology clinic for chronic, irritating bladder symptoms were studied. Evaluation of each subject is composed of lower urinary tract symptoms (LUTS), bladder diary entries, and urodynamic studies, which also included an ice water test (IWT) to detect the presence of a C-fiber mediated micturition pathway. Interstitial cystitis (IC) was diagnosed with post-hydrodilatation cystoscopic findings of glomerulations and a KCl test. RESULTS: These patients complained predominantly of overactive bladder symptoms (OAB), including frequency (n=20, 87%), nocturia (n=16, 66%), and urgency (n=12, 52%). Based on the aforementioned evaluations, four patients (17%) had polyuria with normal bladder function, nine patients (39%) had detrusor overactivity (DO), seven patients (32%) had bladder hypersensitivity (including two patients (9%) diagnosed with IC), and three patients (13%) had negative findings. Ice water instillation neither elicited novel involuntary contractions, both in those with or without DO. Five of the six patients (83%) with DO versus one of the four patients (25%) without DO responded to antimuscarinic therapy. CONCLUSIONS: Various factors contribute to the irritating bladder symptoms in patients with SS, with DO being predominant. The LUTS developed in patients with SS are not due to any specific single etiology and that each patient must be individually carefully evaluated.
20701954 Atypical neurologic complications in patients with primary Sjögren's syndrome: report of 2011 Feb BACKGROUND: Neurologic involvement occurs in approximately 25% of patients with primary Sjögren's syndrome. Manifestations are diverse and can affect the entire neuroaxis. Central nervous system dysfunction involves the brain as well as the spinal cord and may recur over time. Due to a variety of presentations, Sjögren's syndrome with neurologic involvement may be difficult to diagnose. METHODS: We report 4 cases of patients with primary Sjögren's syndrome who presented with atypical neurologic manifestations. RESULTS: The first case describes a patient with a pseudotumoral lesion. The second patient was a 54-year-old woman suffering from a multiple mononeuropathy. The third case describes a 66-year-old man whose primary Sjögren's syndrome presented as progressive multiple sclerosis, and the fourth case reports a 57-year-old woman patient suffering from myelitis along with progressive cognitive disorders. CONCLUSIONS: Neurologic impairment in Sjögren's syndrome is probably underestimated and the diagnosis is often delayed. Primary Sjögren's syndrome should be suspected in patients presenting with atypical clinical and radiologic neurologic manifestations.
20452466 The point on the ongoing B-cell depleting trials currently in progress over the world in p 2010 Jul Conventionnal therapy (moisturizers, pilocarpine, Cevimeline, local Cyclosporine, and hydroxychloroquine) remains the basis for the treatment of primary Sjögren's syndrome (pSS) but they do not modify the course of the disease. Rituximab is currently the most fully evaluated biologics in pSS. Open-label studies suggest that Rituximab is well tolerated (although infusion-related reactions and serum sickness remain possible), induces a rapid depletion of B cells in the blood and salivary glands, and could improve early active pSS or pSS with active extra glandular involvement. Two small double blind randomized studies have been conducted and now published, demonstrating its efficacy on fatigue and sicca syndrome in early disease. Two large double blind studies are currently ongoing or planned: The TEARS study (Tolerance and EfficAcy of Rituximab in primary Sjögren syndrome) in France, is currently including 120 patients having either a recent and active disease and/or at least one extraglandular severe signs. The 'TRACTISS' Study (Anti-B-Cell Therapy In Patients With Primary Sjögren's Syndrome), in UK, will include 100 patients having anti-Ro/La antibodies, reduced basal secretion but an increased salivary flow with stimulation, within 10years of diagnosis, symptomatic oral dryness, fatigue and at least one systemic feature.
20013285 [Current therapeutic options in Sjögren's syndrome]. 2010 Feb Sjögren's syndrome is a systemic inflammatory-rheumatic disorder of hitherto unknown origin and, hence, adequate therapy options are not available in most cases. Treatment of sicca symptoms in Sjögren's patients is primarily symptomatic. Glucocorticoids, NSAIDs and/or immunosuppressive drugs may be used for the treatment of extraglandular manifestations or complications. Although there have been few clinical studies to date, new insights into the pathogenesis of this disorder may permit novel therapeutic strategies. Targeting B-cell candidates as a new therapeutic option in this entity has shown promising results. B-cell-depletion using Rituximab has been tested in initial clinical trials for the treatment of Sjögren patients, both with and without associated B-cell non-Hodgkin-lymphoma; however, further studies as well as reliable outcome criteria are needed. Further therapeutic options are currently in development or early clinical testing.
19889514 Characteristics of the minor salivary gland infiltrates in Sjögren's syndrome. 2010 Jun Sjögren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with variable degree of lymphocytic infiltration of the affected organs (primarily salivary and lacrimal glands) and broad clinical manifestations. Minor salivary gland (MSG) lesions mainly consist of T and B cells, while antigen-presenting cells have been reported in heavy infiltrates. Evidence suggests that the infiltrate composition differs according to lesion severity; however, these differences are not well-defined. To investigate the differential distribution of the major infiltrating mononuclear cell (MNC) types in SS-lesions of variable severity, total-T, CD4(+)-T, CD8(+)-T, Treg, and B cell, macrophage (MPhi), interdigitating (iDC) and follicular dendritic cell (fDC), and natural-killer (NK)-cell incidence (%-total infiltrating MNC) was analyzed in MSG biopsies with mild (n = 11), intermediate (n = 13) or severe (n = 15) lesions. T cells, CD4(+)-T cells and Tregs, B lymphocytes, MPhis and iDCs were significantly different among MSG tissues with mild, intermediate or severe inflammatory lesions, while CD8(+)-T cell, fDC and NK cell incidence was not correlated with lesion severity. T cell, CD4(+)-T cell, T/B cell ratio and iDC incidence was negatively, whereas B cell and MPhi incidence was positively correlated with infiltration grade and biopsy focus score. Tregs predominated in intermediate lesions. Multivariate analysis revealed several associations between the incidence of each infiltrating MNC-type and disease manifestations, implying an involvement of local immune responses in systemic disease features. Our findings support that the distribution of infiltrating MNCs at the SS-lesions varies according to lesion severity and correlates with disease manifestations. The significance of this differential distribution and the underlying aetiopathogenic factors need to be elucidated.
20655712 Dendrobium candidum extract increases the expression of aquaporin-5 in labial glands from 2011 Jan 15 This study aimed to investigate the mechanism of Dendrobium candidum extract in promoting expression of aquaporin-5 for treatment of Sjögren's syndrome (SS). Sixteen patients with SS suffered from deficient secretion of saliva due to an autoimmune destruction of salivary glands leading to dry mouth symptoms (xerostomia). However, glandular dysfunction also occurred without destruction. Based upon its abnormal distribution in SS salivary glands, a potential role of the water channel protein aquaporin-5 (AQP-5) in the pathogenesis of SS was proposed. After oral administration of D. candidum extracted liquid (DCEL) for 1 week, saliva and salivary gland biopsies from labial glands of patients were collected and examined by employing immunoreactivity and immunohistochemistry techniques. Results showed that salivary secretion increased by about 65% in patients treated with DCEL as compared with the control group. Higher labeling indices (percentage of acinus area immunoreactive for AQP-5) in the biopsies were found in SS patients who had taken DCEL. This study demonstrated that D. candidum would regulate the expression of AQP-5 in labial glands of SS patients and thereby promoted secretion of saliva to improve dry mouth symptoms.
20554086 [Primary Sjögren's syndrome and neuromyelitis optica]. 2010 Sep Neuromyelitis optica (NMO) is characterized by the association of optic neuritis and myelitis without any other neurological signs. In 30 % of the cases, NMO is associated with a systemic disorders. We report two cases of NMO associated with primary Sjögren's syndrome that was diagnosed during an acute flare of NMO. The relationship between NMO and Sjögren's syndrome has not been clearly identified. This association likely reflects the coexistence of two autoimmune disorders. The prognosis of NMO appears to be more severe in patients having coexisting Sjögren's syndrome, which renders useful to search for this association in patients with neuromyelitis optica.
19668890 Primary Sjogren's syndrome with central nervous system involvement. 2009 Aug OBJECTIVE: To describe the clinical, laboratory, and radiological features of Primary Sjogren's syndrome (PSS) with central nervous system (CNS) involvement. METHODS: A retrospective case series of 12 female patients with PSS and CNS involvement at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia from 1991-2009. The diagnosis of PSS is defined by the American-European Diagnostic Criteria. We analyzed the clinical, radiological, and immunological features. RESULTS: The mean age was 40 years (range 16-58 years); all patient were females and presented with active neurological symptoms. The neurological involvement preceded the classic sicca symptoms (33%). Eight patients (66%) presented with myelopathy, 9 patients (75%) had optic neuritis, and the rest had variable neurological signs. Immunological tests (anti-Sjogren's syndrome A and anti-Sjogren's syndrome B) were high in 7 patients (58%). Minor salivary gland biopsy revealed inflammatory cell infiltrate in 11 patients (92%). Brain MRI showed scattered white matter changes in 7 patients (58%). Spine MRI showed multiple foci of hyperintensity in T2-weighted image in 6 patients (50%), and long segment of hyperintensity at the cervical spinal cord in 2 patients (16%). CONCLUSION: Our findings demonstrate that CNS involvements in PSS have great clinical variability and could precede the classic sicca symptoms by years. Primary Sjogren's syndrome can mimic multiple sclerosis (primary progressive multiple sclerosis or relapsing remitting multiple sclerosis), therefore a screening test for PSS should be considered in suspected cases. A well-defined management protocol awaits studies with larger case numbers.