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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16460489 Rheumatoid-like nodules in the spleen: new extraintestinal manifestation of Crohn's diseas 2006 Jan A 26-year-old, HLA-B27 positive man with steroid dependent Crohn's disease presented with abdominal lymphadenopathy and multiple abscess-like masses in the spleen and liver 2 years after the initial diagnosis. A biopsy of one of the liver lesions showed epitheloid cell granuloma, no microorganisms were detected despite intensive investigations. The liver lesions and the lymphadenopathy repeatedly disappeared completely in response to prednisolone pulse therapy while the lesions in the spleen remained practically unchanged. One year later, on immunosuppressive therapy with azathioprine and low-dose prednisolone, the patient's condition exacerbated with development of fever, disseminated arthritides and enlargement of the splenic lesions. Following ineffective antimicrobial treatment, a splenectomy was carried out. Histology showed that the splenic parenchyma was filled with abacterial, rheumatoid granulomas. After a renewed flare-up of severe extraintestinal symptoms, the patient is now asymptomatic on immunosuppressive therapy with azathioprine and prednisolone. Abdominal lymphadenopathy is no longer present and the liver lesions are regressing. The intermittent course and the positive response to immunosuppressive therapy point to a further extraintestinal manifestation of Crohn's disease.
17937465 Anticentromere antibodies identify patients with Sjögren's syndrome and autoimmune overla 2007 Nov OBJECTIVE: To assess the prevalence and clinical and immunological significance of anticentromere antibodies (ACA) in patients with primary Sjögren's syndrome (pSS). METHODS: We retrospectively investigated the prevalence of ACA in patients with SS. We compared ACA-positive SS patients with ACA-negative pSS patients. RESULTS: The prevalence of ACA among patients with pSS was 4.7% (10/212). Among the patients with SS and an associated autoimmune disease, 10 patients had ACA and limited cutaneous sclerosis (SSc). Clinical and immunological patterns did not differ between the 10 pSS patients with ACA alone and the 10 SS patients with ACA and SSc, except for presence of limited cutaneous SSc (lcSSc). Moreover, all ACA-positive sera recognized centromere protein-B on ELISA, regardless of the presence of SSc. The entire SS-ACA group (n = 20) showed greater frequency of Raynaud's phenomenon, objective xerophthalmia, peripheral neuropathy, and additional autoimmune disorders, especially primary biliary cirrhosis, compared to pSS patients without ACA (p = 0.005, p = 0.04, p = 0.001, p = 0.05, p < 0.0001, respectively). SS patients with ACA less frequently showed anti-SSA or anti-SSB antibodies than those without ACA (p = 0.0002, p = 0.01, respectively) but greater prevalence of autoantibodies other than anti-SSA/SSB or ACA (p = 0.001). CONCLUSION: Clinical and immunological features of SS were largely similar among SS patients with ACA with and without SSc. However, the presence of ACA among patients with SS allows identification of a subset of patients with "SS overlap syndrome," who show a wide diversity of autoimmunity, encompassing but not limited to SSc.
17265991 57-year-old Asian-American man with Kikuchi's disease. 2006 Nov Kikuchi's Disease (KD) is a subacute necrotizing lymphadenitis more commonly reported from Asia. The classic presentation includes low-grade fever and cervical lymphadenopathy in a previously healthy woman. The ratio of affected women to men is 4:1 with the average age of onset less than 30 years. We report a case of KD in a 57-year-old Asian-American man whose presentation is associated with Adult Still's Disease.
17149766 Salivary gland mucosa-associated lymphoid tissue lymphoma in 2 patients with Sjögren's sy 2007 Feb We report 2 cases of mucosa-associated lymphoid tissue lymphoma of the salivary glands, complicating Sjögren's syndrome. The sonographic and histological features are described in depth. The use of sonography as a diagnostic aid in such patients is discussed.
17062438 The prevalence of Sjögren's syndrome in adult women. 2006 Sep OBJECTIVES: The aim of this study was to determine the prevalence of primary Sjögren's syndrome (pSS) according to European criteria (1993) and to the US-European Consensus Group (US-EU) criteria (2002) in adult women in Bornova, Izmir, Turkey. MATERIALS AND METHOD: The study was designed as a two-phase cross-sectional survey consisting of a baseline questionnaire and collection of blood samples and clinical examination. In the initial phase, positivity for autoantibodies Ro(SS-A), La(SS-B), rheumatoid factor (RF), and anti-nuclear antibodies (ANA) was determined, and in the clinical phase, clinical examination, salivary and ocular tests were performed. Minor salivary gland biopsy was performed for those who had at least three of these five criteria positive. RESULTS: In our sample the prevalence of SS was 1.56% [95% confidence interval (CI) 0.92-2.66] according to the European criteria and 0.72% (95% CI 0.33-1.57) according to the US-EU criteria. CONCLUSION: To prevent the loss in diagnosis of pSS, the addition of ANA, RF, and tear break-up time (BUT) tests to US-EU criteria would be appropriate.
17149056 Response to application of ice may help differentiate between gouty arthritis and other in 2006 Dec AIM: The aim is to determine whether response to topical ice versus heat differentiates between patients with gout versus other arthritides. METHODS: The first 150 patients seen in our clinic with joint pain from February 2004 onward were asked to fill out questionnaires regarding their response to heat and ice. Patients who responded that topical ice eased their pain and who did not have a diagnosis of crystal-induced arthritis were asked to have a joint aspiration if they had active synovitis on presentation to the clinic. RESULTS: Of 150 completed questionnaires, 26 patients never tried heat or cold as adjuvant treatment for their arthritis. The remaining 124 patients were divided into 6 groups: patients with crystal-proven gout (n = 20), rheumatoid arthritis (RA; n = 32), osteoarthritis (OA; n = 32), other forms of inflammatory arthritis (n = 18), and soft tissue conditions (n = 22). None of the patients with gout benefited from topical heating of their affected joints and all preferred topical ice (P < 0.001). Most patients with RA preferred heat (n = 24). Of 4 patients with RA who preferred topical ice, 3 had effusions and arthrocentesis was performed. Intracellular monosodium urate (MSU) crystals were seen in 2 and intracellular calcium pyrophosphate dihydrate (CPPD) crystals were seen in one patient raising questions about coexistence of 2 diseases or previous misdiagnoses. Most patients with OA preferred heat (n = 28). A significantly higher percentage of the patients with gouty arthritis found that topical ice helped relieve their joint pain as compared with patients with RA (P = 8 x 10(-11)) and other inflammatory arthritides (P = 3 x 10(-8)). DISCUSSION: Heat and cold are adjuvant treatments for arthritis. In gouty arthritis, cold applications are a useful adjunct to treatment and may help discriminate patients with gout from other forms of inflammatory arthritis.
19043267 Sjögren's syndrome with multiple cystic lesions and pulmonary arteriovenous fistulae. 2008 A patient presented with Sjögren's syndrome associated with pulmonary multiple cystic lesions and a pulmonary arteriovenous fistulae. A histological examination of the lungs during the autopsy revealed the stenosis of the bronchiole lumens with hyperplasia of goblet cells, proliferation of smooth muscles in the inner wall of the bronchioli and retention of mucus in the airway lumens. These small airway changes were accompanied with chronic inflammatory changes of the airways in Sjögren's syndrome and led to the formation of cystic lesions via a ball-valve mechanism. Arteriovenous fistulae were situated around the cystic lesions. There may have been a correlation between the formation of the fistulae and cysts, but no mechanism was indicated in the histological findings. This report reveals that chronic inflammatory changes of the airways in Sjögren's syndrome are sufficient to cause the formation of cystic lesions.
18689326 [Fever with skin rash and polyarthralgia in a genetically black-skinned woman]. 2008 Jun Adult onset Still's disease (AOSD) is a systemic disorder characterized by intermittent fever, evanescent rash, polyarthralgia or arthritis, and neutrophilic leucocytoclasis. Appearance of skin rash during fever episodes is the characteristic feature. An atypical form of AOSD with a fixed pigmented skin rash was described in 1994. Prognosis of the atypical form is thought to be more severe than that of the classic form. The purpose of this report is to describe the first case of atypical AOSD in a genetically black-skinned woman. Treatment required administration of high-dose systemic corticosteroids.
17992588 Animal models of Sjögren's syndrome. 2007 Jun Sjögren's syndrome is an autoimmune, chronic inflammatory disease characterized by focal mononuclear cell infiltration of exocrine tissues, accompanied by loss of secretory function. The pathogenesis of autoimmune diseases is complex and, therefore, difficult to study in vitro. As of today, the role of initiating factors remains obscure, clinical symptoms develop late, and there are no tests for early diagnosis of SS. Hence, the disease is difficult to detect and treat. Animal models may provide insights into the identification of target antigens, narrowing the relevant pathological immune mechanisms, and to study the evolution of tissue pathology. This review summarizes current knowledge on murine strains, both spontaneous and induced models, used to study Sjögren's syndrome. Special attention is paid to the characteristics of different strains regarding their properties to mimic specific aspects or stages of the disease.
17628907 [Pulmonary arterial hypertension revealing pseudolymphoma associated with Sjogren's syndro 2006 INTRODUCTION: The authors related a right heart failure related to a primitive pulmonary arterial hypertension without past medical. METHODS AND RESULTS: This diagnosis has been noticed on the cardiac catheterism as well as the cardiac echography (no shunt). Two years later systemic anomalies such as polyarthritis and salivary glands disease were noticed. The Biopsy revelated a primitive Gougerot-Sjorgen pseudolymphomas syndrom. CONCLUSION: Three years under conventional treatment were a failure as the evolution of the disease resulted to death.
17188404 [Painful thoracic neuropathy disclosing Sjögren's syndrome: first report]. 2007 Mar INTRODUCTION: Thoracic neuropathy is rare, and is usually associated with diabetes mellitus. We report a first case of isolated multi-metameric thoracic neuropathy revealing Sjögren's disease. EXEGESIS: A 64-year old man consulted for symptoms suggesting a progressive and extensive (from T7 to T10) bilateral thoracic neuropathy. Diabetes mellitus and other causes of neuropathy were excluded. Spinal MRI, electromyography and CSF analysis were normal. Though the patient had no sicca syndrome symptoms, the diagnosis of Sjögren's syndrome was made on hypergammaglobulinemia, elevated ACAN (1/5000) with anti-SSA specificity and a grade III minor salivary gland biopsy. He improved spectacularly on corticosteroids (prednisone, 1 mg/kg/d). Sicca syndrome became clinically evident in April 2006. CONCLUSION: Pure sensitive thoracic neuropathy can reveal Sjögren's syndrome.
16614610 [Anti-TNF alpha in the treatment of psoriatic arthritis]. 2006 Apr Psoriatic arthritis is an inflammatory and possibly destructive form of arthritis. As in rheumatoid arthritis and ankylosing spondylitis, the use of biological therapy in psoriatic arthritis is a therapeutic revolution: both articular and cutaneous efficacy have been shown, and some improvement is visible on radiography. The benefit-risk ratio will improve when we learn to identify more accurately the patients likely to benefit from these treatments.
17056149 Current status of gene delivery and gene therapy in lacrimal gland using viral vectors. 2006 Nov 15 Gene delivery is one of the biggest challenges in the field of gene therapy. It involves the efficient transfer of transgenes into somatic cells for therapeutic purposes. A few major drawbacks in gene delivery include inefficient gene transfer and lack of sustained transgene expression. However, the classical method of using viral vectors for gene transfer has circumvented some of these issues. Several kinds of viruses, including retrovirus, adenovirus, adeno-associated virus, and herpes simplex virus, have been manipulated for use in gene transfer and gene therapy applications. The transfer of genetic material into lacrimal epithelial cells and tissues, both in vitro and in vivo, has been critical for the study of tear secretory mechanisms and autoimmunity of the lacrimal gland. These studies will help in the development of therapeutic interventions for autoimmune disorders such as Sjögren's syndrome and dry eye syndromes which are associated with lacrimal dysfunction. These studies are also critical for future endeavors which utilize the lacrimal gland as a reservoir for the production of therapeutic factors which can be released in tears, providing treatment for diseases of the cornea and posterior segment. This review will discuss the developments related to gene delivery and gene therapy in the lacrimal gland using several viral vector systems.
18836930 Periocular pseudo-rheumatoid nodules commonly affect the orbital rim. 2008 PURPOSE: To describe the typical presenting clinical characteristics and histopathology for periocular pseudo-rheumatoid nodules. METHODS: Clinical case-note and histopathological review for patients presenting to the Orbital Clinic at Moorfields Eye Hospital between 1994 and 2002. RESULTS: Four females with biopsy-proven periocular pseudo-rheumatoid nodules presented between the ages of 22 and 33 years (mean 26.8 years), having a 4-month to 3-year history of newly formed (or recurrent) subcutaneous nodules-these overlying the superotemporal orbital rim and rarely tender. One patient had insulin-dependent diabetes for 22 years and one patient had bilateral disease. The masses were excised in all patients, with a minor recurrence in one, not requiring further treatment; one patient defaulted from follow-up. CONCLUSIONS: Periocular pseudo-rheumatoid nodules appear to typically present in young females, possibly more commonly with type I diabetes mellitus, and form a rather characteristic slowly growing, firm, occasionally slightly tender, subdermal nodule overlying the superolateral rim of the orbit. Surgical excision improves the condition in many cases, although spontaneous regression might also occur.
17135704 Preliminary dielectric studies of knee swelling fluid in the case of arthritis, which is h 2006 Dec This study addresses the problems connected with knee joint inflammatory swelling diagnosis, especially cases which have difficulty meeting rheumatic and laboratory criteria. A percentage of patients were considered who met the clinical criteria of the Association of Rheumatoid Arthritis (ARA), proceeded without any deviations within the range of rheumatoid factor (RF) laboratory results, and where only serum non-specific immuno-complexes (CIC) increased. The decision to execute a more effective treatment variant (salazopirin, for example, instead of NSAID), required criterial reliability in practice. The purpose of the study was to attempt to find physiochemical distinguishing features in the exudative liquid taken from the knee joints of two groups of patients: group A meeting the clinical criteria of immunological inflammation and a negative rheumatoid factor, and group B with other inflammation concerned with degenerative changes and with negative rheumatoid factor tests. The main area of interest was the question of whether dielectric scanning enables the distinction between immunology and degenerative inflammatory liquid. Analyses of dielectric joint liquid parameters in the domains of frequency and temperature made it possible to observe recurring changes in the shapes of diagrams in the event of the existence of immunological complexes in the studied environment. We found that (1) dielectric scanning diagrams after joint liquid analyses showed similar negative dielectric parameters in group A (inflammatory), B (degenerative) and C (post-accident) with scanning frequencies of about 10,000,000-3501,300 Hz and similar positive parameters of about 3501,300-1593,700 Hz, but qualitative difference dielectric parameters in group A with a frequency of 1593,700-1225,900 Hz, probably dependent on the inflammatory gamma-globulin concentration; (2) higher dielectric parameters (groups B, C) at a scanning frequency of 94,300-57,600 Hz probably dependent on ion concentration; (3) parametric changes of frequency scanning differentiating the diagrams between groups A and B, C, defining the outline pilot study recommended ranges of frequency and temperature testing for further investigations.
17847114 IgM, IgG, and IgA rheumatoid factors in pigeon hypersensitivity pneumonitis. 2007 The association of rheumatoid factor (RF) and lung disease in several immunologically mediated conditions has suggested that it may be physiopathologically relevant. Since previous reports in hypersensitivity pneumonitis (HP) have dealt mainly with the immunoglobulin M (IgM) RF measurement, we studied such antibody activity in other immunoglobulins, to determine the IgG and IgA RF levels in pigeon-HP, and in asymptomatic breeders (AB) and rheumatoid arthritis (RA) as controls. RFs were measured in 35 HP patients, 41 AB, 31 RA controls, and 55 healthy donors by enzyme-linked immunosorbent assay (ELISA) using human or rabbit immunoglobulin G (IgG), anti-IgM, F(ab')2 of IgG, and IgA F(ab')2 conjugates. An affinity chromatography, fragment crystallizable (Fc) preparations of IgG, pepsin digestion, and Western blots were used to confirm RF specificity. We also evaluated anti-avian antibodies (AA) and cross-reacting antibodies. The HP group revealed positive IgM (51.4%), IgG (31.4%), and immunoglobulin A (IgA) (34.2%) RF tests, and these antibody values exceeded the AB reference levels (P<0.02). HP and RA showed a similar frequency and distribution of RFs. Possible immunoassay interferences were excluded. As in other immunologically mediated diseases, IgG and IgA RFs may play a pathogenic role in HP, amplifying the inflammatory reaction, immune-complex formation, and complement activation. IgM-RF producing cells that have been implicated in the presentation of self and foreign antigens, and T-cell activation might induce the isotype switching of RFs.
16697230 Matrix metalloproteinase-9 (gelatinase B) deficiency leads to increased severity of Staphy 2006 May Matrix metalloproteinases constitute a family of structurally related endopeptidases that are crucial for the normal turnover of the extracellular matrix. Elevated levels of MMP-9 have been demonstrated in synovial fluids of rheumatoid arthritis patients, and a correlation with the severity of the disease has been described. The aim of this study was to explore the impact of MMP-9 expression on joint inflammation and destruction in a model of bacterially induced septic arthritis. MMP-9 knock-out mice and C57Bl6 congenic controls were inoculated intravenously or intra-articularly with Staphylococcus aureus. Arthritis was evaluated clinically and by means of histology. Zymographic analyses were performed to study ex vivo induction of MMP-9 following exposure to S. aureus. The MMP-9 knock-out mice displayed a significantly higher frequency and severity, but not destructivity, of arthritis than did the wild-type mice. The knock-out mice also proved to harbour an increased number of bacteria locally in joints and systemically in kidneys, possibly by impaired extravasation and recruitment of leukocytes and a deficient early defence against infection. Our findings indicate that deficiency in MMP-9 increases the degree of joint inflammation due to decreased bacterial clearance.
19132149 [Dynamic contrast-enhanced magnetic resonance imaging of the wrist in early arthritis]. 2008 Oct OBJECTIVES: MRI has been proposed as the imaging method of choice to evaluate the long-term outcome in patients with early arthritis. The role of dynamic MRI, performed at presentation, in predicting the outcome of patients with early arthritis has been addressed in the present study. METHODS: 39 patients with early arthritis, involving at least one wrist, were studied with clinical visits and laboratory investigations, every 3 months. Dynamic MRI was performed with a low-field (0.2T), extremity-dedicated machine (Artoscan, Esaote, Genova, Italy) equipped with a permanent magnet and with a dedicated hand and wrist coil. During the intravenous injection of Gd-DTPA, twenty consecutive fast images of 3 slices of the wrist were acquired. The synovial contrast enhancement ratio was calculated both as rate of early enhancement (REE) per second during the first 55" and as relative enhancement (RE) at t seconds. RESULTS: In our cohort of patients, REE and RE were significantly lower than those observed in a historical cohort of 36 patients with active rheumatoid arthritis. In univariate analysis, low RE predicted complete remission of arthritis. In multivariate analysis, fulfillment of RA criteria during follow-up was predicted by high RE. The need for immunosoppressive treatment at the end of follow-up was predicted by both low RE and high REE. CONCLUSIONS: Dynamic MRI may be used to predict several outcomes of early arthritis involving the wrist.
18926560 The potential of liposomal drug delivery for the treatment of inflammatory arthritis. 2009 Dec OBJECTIVE: To review the use of liposomes as a delivery agent in inflammatory arthritis. METHODS: The literature on liposomes and liposomal drug delivery for the treatment of inflammatory arthritis was reviewed. A PubMed search of articles in the English-language journals from 1965 to 2007 was performed. The index words used were as follows: "rheumatoid arthritis," "liposomes," and "targeted delivery." Papers identified were reviewed, abstracted, and summarized. RESULTS: Liposomes have the capacity to be used as delivery and targeting agents for the administration of antirheumatic drugs at lower doses with reduced toxicity. In other areas of medicine, the pace of progress has been rapid. In the case of infectious diseases and cancer, liposomal drug delivery has progressed and developed into commercially viable therapeutic options for the treatment of fungal infections (amphotericin B), or metastatic breast cancer and Kaposi sarcoma (doxorubicin, daunorubicin), respectively. In arthritis, the efficacy of prednisolone-loaded long-circulating liposomes is currently being evaluated in a phase II clinical trial. Liposome's application to arthritis is still in its infancy but appears promising as new patents are filed. With improvements in liposomal formulation and targeted synovial delivery, liposomes offer increased therapeutic activity and improvement in the risk-benefit ratio. CONCLUSION: Recent research into synovial targets and improved liposomal formulations continues to improve our capacity to use liposomes for targeted delivery. With time, this approach has the potential to improve drug delivery and reduce systemic complications.
16755040 F1 hybrid mice (BALB/c x DBA/1) are resistant to collagen-induced arthritis with beta-gluc 2006 Jun Collagen-induced arthritis (CIA) is an experimental model of rheumatoid arthritis (RA) used for studying the clinical, immunological and genetic factors of the disease. Many studies of genetic susceptibility to CIA have been performed, usually with two strains of mice, DBA/1 and B10.RIII, since they are highly susceptible to CIA. Furthermore, F1 hybrid mice of susceptible and resistant strains reportedly develop arthritis. Recently, we reported that particles of beta-glucan, OX-CA, prepared from Candida albicans by NaClO-oxidation, acted as an adjuvant for CIA. Although, there have been many studies about the relationship between antigen and the major histocompatibility complex (MHC) in F1 hybrid mice, little is known argument about susceptibility to adjuvants. Therefore, we checked the susceptibility of F1 hybrids to CIA using OX-CA as an adjuvant. BALB/c and DBA/1 were mated to generate F1 hybrids which were then immunized with type II collagen (CII) plus Freund's complete adjuvant (FCA) or OX-CA. The results showed that F1 hybrids injected with CII plus FCA developed severe arthritis at an incidence ratio 80%, versus only 20% in mice injected with CII plus OX-CA. Furthermore, levels of anti-CII antibody, especially of the IgG2a subclass, in sera from mice treated with CII plus OX-CA were significantly low. Susceptibility to CIA might depend on not only MHC but also the adjuvant used for immunoactivation.