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ID PMID Title PublicationDate abstract
18762861 A case report of a patient with refractory adult-onset Still's disease who was successfull 2009 Interleukin-6 overproduction is pathologically involved in adult onset Still's disease (AOSD). We successfully treated a man with refractory AOSD utilizing tocilizumab. Tocilizumab was discontinued after 15 doses due to intestinal bleeding, but the efficacy was sustained over 21 months. Tocilizumab was readministered safely upon recurrence and showed similar efficacy over 6 years. Corticosteroid and NSAIDs could be discontinued and intestinal bleeding was no more observed. Tocilizumab can be a therapeutic option for AOSD.
19601524 [A case of Sjögren syndrome with nifedipine-induced pneumonia]. 2009 Jun A 54-year-old woman started to take nifedipine orally for hypertension on February 18, 2006. From April 10, 2007, fever, tachycardia and chest pain appeared. Chest radiography showed a consolidation shadow in the right upper lobe. Administration of antibiotics was started because bacterial pneumonia was suspected. After the administration of antibiotics, the condition of the patient was aggravated and the consolidation shadow in the chest radiograph increased. Consequently, she was hospitalized for examination. Transbronchial lung biopsy was carried out on April 27, 2008. Pathological analysis revealed organization and inflammatory cell infiltration was observed in alveoli. Eosinophils were increased in the bronchial washing fluid. After halting administration of all drugs, the fever was alleviated. Since nifedipine was positive in DLST, drug-induced pneumonia caused by nifedipine was diagnosed. Salivary-gland biopsy was carried out on May 25, 2008 on the suspicion of Sjögren syndrome, because she continued to complain of dryness in the mouth and eyes. The pathological findings were consistent with Sjögren syndrome. To the best of our knowledge, there has been no report of drug-induced pneumonia caused by nifedipine. Since the case was complicated with Sjögren syndrome, some immunological dysregulation might have been a factor. In cases of lung impairment caused by a drug, it is necessary to consider the possibility of a immunologic disorder.
19260540 [A case of lymphocytic interstitial pneumonia complicated with primary Sjögren's syndrome 2009 Feb We encountered a rare case of lymphocytic interstitial pneumonia (LIP) complicated with primary Sjögren's syndrome (SjS), followed by chest CT scanning for a long period of time. A 54-year-old man with hemoptysis was admitted to our hospital in December, 2001. A diagnosis of SjS was made based on elevation of anti-SS-B/La antibody titer in serum in combination with diagnosis of keratoconjunctivitis sicca and xerostomia on a Schirmer test and a lip biopsy, respectively. Subsequent histopathological diagnosis by open lung biopsy showed LIP. Chest CT in September, 1995 at previous hospital revealed ground-glassed opacity (GGO), small nodules, thickened bronchovascular bundles and cyst formation in lungs. Chest CT was performed every year until 2008, when remarkable progression from thickened bronchovascular bundles accompanied by nodular opacities to an air-space consolidation in the right lower lobe was observed. Also, appearance of cyst formation in the right middle lobe, nodular lesions and GGO in the left lower lobe were noticed. Although the nodular opacities and GGO improved after an administration of corticosteroid (PSL 0.5 mg/kg/day), little improvement in the consolidations and cyst formation was demonstrated. In conclusion, it was suggested that differences among CT findings of LIP may be important for evaluating of efficacy of treatment by steroid agents for LIP associated with SjS.
19487273 Pattern of joint involvement and other disease characteristics in 634 patients with arthri 2009 Jul OBJECTIVE: To investigate the distribution of joint involvement in a cohort of patients with very recent onset arthritis and describe the disease characteristics in these patients. METHODS: A very early arthritis clinic (NOR-VEAC) was established as a multicenter study. General practitioners were asked to refer patients presenting with at least 1 swollen joint of maximum 16 weeks' duration. Clinical and laboratory markers were examined. RESULTS: We included 634 patients during the first 3 years, with mean (25th-75th percentile) arthritis duration of 30 (11-63) days. Monoarthritis was present in 243 (38.3%) patients, 216 (34.1%) had oligoarthritis, and 175 (27.6%) polyarthritis. Patients with polyarthritis were older, had longer duration of arthritis, and were more frequently anti-cyclic citrullinated peptide antibody and rheumatoid factor-positive. Patients in all 3 joint pattern groups (mono-/oligo-/polyarthritis) reported substantial effect on physical function, pain, and fatigue and had elevated levels of acute-phase reactants. Knee or ankle arthritis was most frequent in patients with mono- and oligoarthritis, whereas small joint involvement was most frequent in patients with polyarthritis. CONCLUSION: Patients with recent-onset arthritis report a substantial influence on health status. Mono- and oligoarthritis are at least as frequent as polyarthritis. Polyarthritic patients more frequently exhibit features associated with a worse outcome.
18971286 LPS activation is required for migratory activity and antigen presentation by tolerogenic 2009 Feb Autoimmune pathologies are caused by a breakdown in self-tolerance. Tolerogenic dendritic cells (tolDC) are a promising immunotherapeutic tool for restoring self-tolerance in an antigen-specific manner. Studies about tolDC have focused largely on generating stable maturation-resistant DC, but few have fully addressed questions about the antigen-presenting and migratory capacities of these cells, prerequisites for successful immunotherapy. Here, we investigated whether human tolDC, generated with dexamethasone and the active form of vitamin D3, maintained their tolerogenic function upon activation with LPS (LPS-tolDC), while acquiring the ability to present exogenous autoantigen and to migrate in response to the CCR7 ligand CCL19. LPS activation led to important changes in the tolDC phenotype and function. LPS-tolDC, but not tolDC, expressed the chemokine receptor CCR7 and migrated in response to CCL19. Furthermore, LPS-tolDC were superior to tolDC in their ability to present type II collagen, a candidate autoantigen in rheumatoid arthritis. tolDC and LPS-tolDC had low stimulatory capacity for allogeneic, naïve T cells and skewed T cell polarization toward an anti-inflammatory phenotype, although LPS-tolDC induced significantly higher levels of IL-10 production by T cells. Our finding that LPS activation is essential for inducing migratory and antigen-presenting activity in tolDC is important for optimizing their therapeutic potential.
20875104 Validity of clinical associations of biomarkers in translational research studies: the cas 2010 INTRODUCTION: Validity of biomarkers may be affected if studies do not include certain features in their design. We evaluated whether translational research studies of potential biomarkers incorporated design features important for valid clinical associations. METHODS: We searched 10 journals for translational studies in six systemic autoimmune diseases published in 2004 through 2009. We included studies that reported associations between laboratory markers and the presence of disease, measures of disease activity, or prognosis. We examined the following design features: age, sex, and race matching; control for effects of treatment on expression of the biomarker; inclusion of patients with both early and late disease, or both active and inactive disease; longitudinal or cross-sectional design; and use of validated activity and damage measures. RESULTS: Among 170 articles, 156 articles examined potential biomarkers for diagnosis, 37 for disease activity assessment, and nine for prognosis; 67 were studies of rheumatoid arthritis (RA); 48, of systemic lupus erythematosus; and 41, of other diseases. Gene-expression profiles were the most commonly examined potential biomarkers (n = 51). Fewer than one half of studies incorporated study-design features important for valid clinical associations. Only 47.4% of studies of biomarkers for diagnosis had groups that were age-matched, 45.5% were sex-matched, and 35.3% controlled for treatment. Studies that examined biomarkers in histologic samples and studies of RA were less likely to include important design features. CONCLUSIONS: Fewer than one half of translational studies of potential biomarkers incorporated design features needed for valid interpretation of clinical associations. Attention to these features could reduce false-positive and false-negative associations.
20495815 Neurological adverse events associated with anti-tumor necrosis factor α treatment. 2010 Sep Anti-tumor necrosis factor alpha (TNF-alpha) drugs have been successfully used for the treatment of rheumatic autoimmune diseases including rheumatoid arthritis (RA), psoriatic arthritis, psoriasis, ankylosing spondylitis (AS), juvenile chronic arthritis, and Crohn's disease. However, they have been associated with different neurological disorders, including alterations of peripheral nerves, multiple sclerosis (MS), optic neuritis (ON) and acute transverse myelitis (ATM). This article reviews the most current aspect regarding neurological adverse events associated with anti-TNF-alpha drugs with emphasis on the possible explanations for this relation and the pathogenic mechanism of TNF-alpha in neurological disorders.
20979564 The efficacy and safety of interleukin-1-receptor antagonist anakinra in the treatment of 2010 Dec IMPORTANCE OF THE FIELD: Systemic juvenile idiopathic arthritis (sJIA) is a debilitating childhood disease presenting with fever, rash and arthritis. Current therapy consisting mainly of corticosteroids, NSAIDs and methotrexate, can be inefficient and is often accompanied by many serious adverse events. Although an IL-1 receptor antagonist (anakinra) seems to be very efficient in case series, it is not registered for use in sJIA. Pediatric rheumatologists all over the world are having a hard time to convince insurance companies to approve off-label use of this drug for their sJIA patients. AREAS COVERED IN THIS REVIEW: Using the MeSH terms 'Arthritis Juvenile Rheumatoid' and 'Interleukin 1 Receptor Antagonist Protein', we searched MEDLINE, EMBASE and reference lists of selected articles. This review is largely based on manuscripts from 2005 to 2010 and abstracts presented at the major (pediatric) rheumatology congresses. WHAT THE READER WILL GAIN: This review summarizes the data of 140 children with sJIA treated with anakinra and enables an understanding in the benefit-risk profile of anakinra in sJIA patients. TAKE HOME MESSAGE: Anakinra has shown to be a very efficient and quick acting medicine in reducing symptoms even in therapy-resistant sJIA patients with typically poor outcomes.
20637613 Tetrahydropyridine derivatives with inhibitory activity on the production of proinflammato 2010 Aug 15 In order to develop a new class of anti-rheumatic drug which inhibits production of proinflammatory cytokines such as TNFalpha, IL-1beta, IL-6, and IL-8, a series of 3-pyridylpyrrole derivatives possessing a bicyclic tetrahydropyridine moiety at the 4-position of the pyrrole ring were synthesized and their pharmacological activities were evaluated. The derivatives were found to have potent inhibitory activities on the production of the cytokines both in vitro and in vivo. Among them, compound 4a, (S)-2-(4-fluorophenyl)-4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole (R-132811), achieved the most promising results in various in vitro and in vivo tests including several rheumatoid arthritis models ((i) inhibition of p38alpha, p38beta, p38gamma, and p38delta MAP kinases: IC(50)=0.034, 0.572, >10, and >10 microM, respectively; (ii) inhibition of TNFalpha, IL-1beta, IL-6, and IL-8 production in human whole blood: IC(50)=0.026, 0.020, 0.88, and 0.016 microM, respectively; (iii) inhibition of LPS induced TNFalpha, IL-1beta and IL-6 production in mice: ID(50)=0.93, 8.63, and 0.11 mg/kg, p.o., respectively; (iv) inhibition of anti-collagen antibody-induced arthritis in mice: ID(50)=2.22 mg/kg, p.o.; (v) inhibition of collagen-induced arthritis in mice: ID(50)=2.38 mg/kg, p.o.; (vi) prophylactic effect on adjuvant-induced arthritis in rats: ID(50)=3.1 mg/kg, p.o.; (vii) therapeutic effect on adjuvant-induced arthritis in rats: ID(50)=4.9 mg/kg, p.o.; (viii) analgesic effect on adjuvant-induced arthritic pain in rats: ID(50)=2.9 mg/kg, p.o.). As a result, compound 4a was chosen as a candidate for further pre-clinical studies.
20008919 Peripheral blood expression profiles of bone morphogenetic proteins, tumor necrosis factor 2010 Feb OBJECTIVE: To assess whether different forms of arthritis and disease activity could be distinguished by peripheral blood expression profiles of bone-regulatory factors including tumor necrosis factor (TNF)-superfamily [TNF-related apoptosis-inducing ligand (TRAIL), the Fas ligand (FasL), and the ligand for herpesvirus entry mediator (LIGHT)] and bone morphogenetic protein (BMP)-family members (BMP-2, BMP-4, BMP-6) as well as osteoblast differentiation gene Runx2. METHODS: Blood cells from healthy controls (n = 25) and patients at different disease stages with rheumatoid arthritis (RA; n = 49), osteoarthritis (OA; n = 17), or spondyloarthritis, including ankylosing spondylitis (AS; n = 27) or psoriatic arthritis (PsA; n = 23), were processed for quantitative polymerase chain reaction. Gene expression was assessed in comparison with control samples, correlated with clinical data of different forms of arthritis, and analyzed for discriminative efficacy between groups by receiver-operation characteristic (ROC) curves. Results were confirmed on diagnostic RA (n = 5) and AS (n = 8) samples. RESULTS: BMP-4, BMP-6, and Runx2 expressions were significantly decreased in patients with RA and OA versus controls. Patients with RA also had decreased FasL and LIGHT expression, while patients with AS had increased Runx2 expression. Negative correlation with disease activity was found for BMP-4, FasL, and Runx2 in RA and for Runx2 in PsA, while positive correlation was found for BMP-4 in PsA. Gene expression was higher in the therapy-resistant form of AS (for BMP-4, LIGHT, and Runx2) and in methotrexate-treated patients in RA (for BMP-2 and LIGHT). ROC curve analysis confirmed discrimination between groups, particularly decreased LIGHT and Runx2 for RA and increased Runx2 for AS. CONCLUSION: Our study identified BMP and Runx2 as possible biomarkers of bone metabolism in several forms of arthritis, while lower FasL and LIGHT were associated with RA. Correlation between gene expression and disease activity may be clinically useful in assessing therapeutic effectiveness and disease monitoring.
21135226 JNK1 controls mast cell degranulation and IL-1{beta} production in inflammatory arthritis. 2010 Dec 21 Rheumatoid arthritis (RA) is a chronic inflammatory disease marked by bone and cartilage destruction. Current biologic therapies are beneficial in only a portion of patients; hence small molecules targeting key pathogenic signaling cascades represent alternative therapeutic strategies. Here we show that c-Jun N-terminal kinase (JNK) 1, but not JNK2, is critical for joint swelling and destruction in a serum transfer model of arthritis. The proinflammatory function of JNK1 requires bone marrow-derived cells, particularly mast cells. Without JNK1, mast cells fail to degranulate efficiently and release less IL-1β after stimulation via Fcγ receptors (FcγRs). Pharmacologic JNK inhibition effectively prevents arthritis onset and abrogates joint swelling in established disease. Hence, JNK1 controls mast cell degranulation and FcγR-triggered IL-1β production, in addition to regulating cytokine and matrix metalloproteinase biosynthesis, and is an attractive therapeutic target in inflammatory arthritis.
19540455 Implications of immunomodulatory interleukins for the hyperimmunoglobulinemia of Sjögren' 2009 A prospective study of 37 patients with pSS and 20 healthy controls was performed to analyze the differences in circulating levels of macrophage-derived and Th1/Th2 cytokines which could explain the hyperimmunoglobulinemia, characteristic of primary Sjögren's syndrome (pSS). Serum levels of interleukin (IL)-6, IL-10, IL-12, gamma-interferon (gamma-INF) and IL-4 were analyzed by a sandwich immunoassay-based protein array system. When compared with the control group, higher levels of IL-6, IL-12 and IL-10 and a lower Th1/Th2 ratio, as demonstrated by the gamma-INF/IL-4 ratio, were detected in patients. The levels of IL-4 were notably higher in pSS patients with monoclonal gammopathy. Serum IL-4 and IL-10 levels and immunoglobulin G concentrations were significantly correlated. In conclusion, patients with pSS show a state of macrophage and T-lymphocyte activation with increased concentrations of cytokines implicated in the differentiation of B cells and secretion of immunoglobulins.
19119981 Autoimmune thyroid diseases in a large group of Hungarian patients with primary Sjögren's 2009 Jan BACKGROUND: Previous studies on relatively small populations of patients with primary Sjögren's syndrome (pSS) suggested an association between pSS and Hashimoto's thyroiditis (HT). As some findings in the literature regarding the relationship between pSS and thyroid disease are contradictory, and there is little information on the sequence of pSS and HT, we conducted a study with a population of patients with pSS that was about three times larger than previously studied populations. Our objective was to determine the prevalence of HT and Graves' disease (GD) in patients with pSS and to assess the sequence of pSS and autoimmune thyroid diseases. METHODS: A total of 479 patients with pSS were retrospectively studied. Thyroid ultrasound and scintigraphy were performed, and serum thyrotropin, free triiodothyronine, free thyroxine, antithyroid peroxidase antibody (TPOAb), and anti-thyroglobulin autoantibody (TgAb) measurements were carried out. Solitary thyroid nodules were investigated by fine-needle aspiration biopsy. RESULTS: Thyroid dysfunction was found in 95 patients (21.25%). Thirty of these patients had HT and 18 had GD. HT predated pSS in eight patients, developed at approximately the same time in seven patients, and followed pSS in 15 patients. Almost all (90%) patients with HT had persistently elevated serum TgAb or TPOAb titers. CONCLUSIONS: An association between HT and pSS was found based on the fact that the frequency of HT was greater among pSS patients (6.26%) than in the general population (1-2%). In contrast, no association between GD and pSS was found. We noted that both HT and GD can appear either before or after the onset of pSS. Since most cases of pSS predate the appearance of autoimmune thyroid diseases it is important to determine if pSS is a predisposing factor for the development of autoimmune thyroiditis.
20946951 Degree of modification of Ro60 by the lipid peroxidation by-product 4-hydroxy-2-nonenal ma 2011 May 15 Our previous work showed that immunization of rabbits with 4-hydroxy-2-nonenal-modified Ro60 (HNE-Ro60) accelerates autoimmunity. We extended this model into mice, hypothesizing that the severity of autoimmunity would be dependent on the degree of HNE modification of Ro60. Five groups of BALB/c mice (10/group) were used. Group I was immunized with Ro60. Groups II to IV were immunized with Ro60 modified with 0.4 mM (low), 2 mM (medium), and 10 mM (high) HNE, respectively. Group V controls received Freund's adjuvant. A rapid abrogation of tolerance to Ro60/La antigens occurred in mice immunized with HNE-modified Ro60, especially in the low and medium HNE-Ro60 groups. Lymphocytic infiltration and significantly high decrement in salivary flow (37%) compared to controls was observed only in the high HNE-Ro60 group, suggesting induction of a Sjögren syndrome-like condition in this group. Anti-dsDNA occurred only in mice immunized with medium HNE-Ro60. This group did not have a significant decrement in salivary flow, suggesting induction of a systemic lupus erythematosus-like manifestation in this group. Significantly high antibodies to Ro60 were found in saliva of mice in the low and medium HNE-Ro60 and the Ro60 groups, as well as anti-HNE Ro60 in the low and medium HNE-Ro60 groups. Understanding the mechanism of this differential induction may help discriminate between these two autoimmune diseases.
20805649 Recurrence of subarachnoid hemorrhage due to the rupture of cerebral aneurysms in a patien 2010 A 52-year-old woman with Sjögren's syndrome presented with multiple cerebral aneurysms, which resulted in recurrent subarachnoid hemorrhage (SAH) manifesting as severe headache. Computed tomography (CT) showed SAH. Cerebral angiography revealed aneurysms of the anterior communicating artery and the left middle cerebral artery. The necks of the aneurysms were successfully clipped. Postoperative course was uneventful and she was discharged without neurological deficit. Thirteen years later, she suddenly lost consciousness and was brought to our hospital. CT demonstrated recurrence of SAH. Cerebral angiography revealed cerebral aneurysms of the right internal carotid artery and the right middle cerebral artery. The clipped aneurysms were stable. The internal carotid artery aneurysm was successfully treated with endovascular coil embolization. However, she regained no neurological function and died. Patients with Sjögren's syndrome may develop cerebral aneurysm complicated with SAH.
19663187 [The role of parotid gland biopsy in early detection of lymphoma in primary Sjogren's synd 2009 AIM: To investigate the incidence of MALT-lymphoma in Sjogren's disease by means of biopsy of the enlarged parotid glands. MATERIAL AND METHODS: The incisional parotid biopsy was performed in 57 primary Sjogren's syndrome (pSS) patients with existing parotid enlargement. The median age was 54 years (range 19-75 years). The median pSS duration was 7 years (range 1-30 years). The palpable parotid enlargement was defined as grade 1 and massive (visional) enlargement of the parotid glands was defined as grade 2. Histologic and immunohistochemical examinations for diagnosis of lymphoma were made. High resolution electrophoresis and immunofixation were performed for detection of monoclonal immunoglobulins in the serum and their free light chains in the urine. RESULTS: Biopsy of the enlarged parotid glands identified MALT-lymphoma in 37 of 57 (64.9%) pSS patients. Of 37 pSS patients with parotid enlargement of grade 2, diagnosis of MALT-lymphoma was made in 89.2%. Of 20 pSS patients who had parotid enlargement of grade 1, MALT-lymphoma was diagnosed in 20%. In patients with grade 1 enlarged parotid glands MALT-lymphoma was identified only in cases with the presence of monoclonal immunoglobulins in the serum and their free light chains in the urine (3 of 4 patients) or in case of disseminated disease (lymphoma involved regional lymph nodes and soft tissues of the face)--1 of 4 patients. In patients with grade 2 enlargement of parotid glands MALT-lymphoma located most frequently in affected parotid glands (69.6%). CONCLUSION: The incisional biopsy of enlarged parotid glands is necessary for detection of MALT lymphoma in pSS patients.
19459558 [Circulating immune complexes, immunoglobulin G, salivary proteins and salivary immunoglob 2009 Mar INTRODUCTION: Sjögren's syndrome (SS) is a chronic autoimmune disorder, with its major clinical manifestations resulting from changes in exocrine glands. OBJECTIVE: The aim of this study was to evaluate serum concentrations of circulating immune complexes (CIC) and immunoglobulin G (IgG), and salivary proteins (SP) and salivary immunoglobulin A (slgA) in 40 patients with SS, and to correlate these values among themselves, as well as with the unstimulated salivary flow rate (USFR) and the duration of disease. METHODS: The total of 40 patients were included in this research. CIC was determined using the solution of polyethylene glycol and IgG with the standard procedure of radial immunodiffusion. SP was investigated by the method of Lowry and slgA was separated from the whole saliva using the method of immune chromatography. RESULTS: The values of most of the studied parameters exceeded the normal range in a high degree: CIC 72.5%, IgG 70%, SP 80%. The concentrations of CIC were significantly higher in the patients with the duration of disease less than 10 years. With the decrease of USFR, the concentration of slgA and IgG were increased with statistical significance. CONCLUSION: The increased prevalence of abnormal values of CIC, IgG and SP indicate that the patients with SS have developed a higher level of immune reactivity. These results could be useful in diagnosis and disease activity monitoring.
20040797 Cryoglobulin evaluation: best practice? 2010 Jan Cryoglobulins are serum immunoglobulins that precipitate at temperatures below 37 degrees C and re-dissolve on warming. Cryoglobulinaemia leads to variable symptoms including characteristic purpura, ischaemia of extremities, renal failure, peripheral neuropathy, abdominal pain secondary to intestinal ischaemia and arthralgias. Cryoglobulin testing is underutilized in clinical practice. It has been neglected in clinical laboratories and by clinicians due to several factors, such as the length of time it takes for serum cryoglobulin analysis to be performed in the laboratory, the perceived difficulty in getting optimal sampling conditions and a failure to appreciate that even apparently low levels of cryoglobulin can be associated with severe symptoms in some patients. The most important variable confounding standardization of cryoglobulin testing is improper sample handling. A recent report critically appraising the current practice of cryoglobulin evaluation in 137 laboratories in Europe by United Kingdom National External Quality Assurance Scheme (UKNEQAS) illustrated the wide variability in practice. Although many clinical laboratories perform cryoglobulin evaluation, there are widespread differences in the methodology used and the care with which this is carried out and this leads to considerable intralaboratory and interlaboratory variability. The most common sources of error are false-negative results due to loss of cryoprecipitate during transport and storage. Better standardization is needed to avoid missed diagnoses and improve the comparability of results. Laboratories should ensure that sample temperature is maintained at 37 degrees C until the serum is separated. In this article, we briefly review the classification and clinical features of cryoglobulins and suggest best practice guidelines for laboratory detection and identification of cryoglobulins.
19574472 Cytokine and autoantibody profiling related to histopathological features in primary Sjogr 2009 Sep OBJECTIVE: To investigate a potential correlation between circulating cytokine and autoantibody levels and histopathological features in subgroups of patients with primary SS (pSS). METHODS: Minor salivary gland biopsies from a cohort of 141 patients fulfilling the American-European consensus classification criteria for pSS were re-examined and grouped according to focus score (FS) and germinal centre (GC) status; serum samples were analysed for autoantibodies, chemokines and cytokines. RESULTS: Of the 115 available biopsies, 18 (16%) lacked characteristic focal mononuclear cell infiltrates [FS < 1 (FS-)] but patients were positive for Ro/SSA and/or La/SSB. IL-17, IL-1RA, IL-15, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, eotaxin, IFN-alpha and IL-4 levels were significantly increased in the 27 (23%) patients with ectopic GC formation (GC+) in the salivary glands compared with the GC- patients (n = 70). In addition, minor differences in cytokine levels were found when comparing age groups. CONCLUSION: Degenerative changes observed in the minor salivary glands of patients with pSS may represent 'burned out' inflammation. The elevated levels of IL-4 found in these patients may influence the reduced salivary flow observed in GC+ patients. Increased titres of Th17-associated cytokines, IL-17, IL-1beta and the IL-23 subunit IL-12p40, may indicate a higher activity of these cells in GC+ patients. Differences in cytokine levels may be utilized when sub-grouping the SS patients into disease phases and may consequently have implications for treatment.
19462335 Prevalence of alpha-fodrin antibodies in patients with chronic hepatitis C infection and S 2009 OBJECTIVE: Hepatitis C virus infection (HCV) is associated with various extrahepatic manifestations. Antibodies against alpha-fodrin are associated with sicca symptoms and may valuable diagnostic markers in patients with primary Sjögren syndrome (SS) lacking Ro antibodies. The frequency and role of alpha-fodrin antibodies in patients with chronic HCV infection are unknown. The aim of this study was to investigate the prevalence of alpha-fodrin antibodies in HCV-infected patients with SS. MATERIAL AND METHODS: Alpha-fodrin antibodies were detected more often in hepatitis C patients (25%; n=142) than in HBV-infected individuals (8%; n=49) and healthy controls (6%; n=174) (p<0.01). Based on these findings, we investigated the frequency of sicca symptoms in a second cohort and studied other antibodies associated with SS. RESULTS: HCV-infected individuals showed sicca symptoms in 53% of cases as determined by the Saxon and Schirmer tests, which was more frequent than in healthy controls (1%, p<0.01) but not in patients with autoimmune liver disease (51%). Antibodies specific for Ro (SS-A) were significantly more common in patients with autoimmune liver disease than in HCV-infected patients and healthy controls (16% versus 1% and 0%, p<0.003). SS was found in 18% of patients with HCV, in 15% of patients with autoimmune liver disease and in 1% of healthy controls. However, we found no correlation between sicca symptoms and the presence of antibodies against alpha-fodrin, Ro and La. CONCLUSIONS: Patients with chronic HCV infection show a high prevalence of sicca symptoms and antibodies against alpha-fodrin. However, neither the frequency nor the severity of symptoms correlated with the presence of alpha-fodrin antibodies.