Browse

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

ID PMID Title PublicationDate abstract
11055826 Clinical and serological aspects of patients with anti-Jo-1 antibodies--an evolving spectr 2000 The aim of this study was to compare ELISA, immunodiffusion and immunoblot for the detection of anti-Jo-1 antibodies, and to investigate the association of the results with clinical manifestations. In two medical centres for rheumatology and one for pulmonology, all patients with suspected connective tissue disease were screened over a 5-year period for anti-Jo-1 antibodies by ELISA. Positive sera were controlled in another laboratory by immunodiffusion. If immunodiffusion was negative, sera were controlled again by ELISA. ELISA-positive immunodiffusion-negative sera were tested by immunoblotting. The patients were characterised clinically, and their clinical signs and symptoms were compared with those of 257 patients with anti-Jo-1 antibodies published in 15 case series and 30 case reports. Twenty-five patients had a positive ELISA test. Fifteen sera were positive by ELISA and immunodiffusion (group 1). Three sera showed high titres in both ELISA tests with negative immunodiffusion and immunoblot (group 2). Seven sera showed low titres in both ELISA tests. The results were negative in the other tests (group 3). Patients in groups 1 and 2 could be classified as Jo-1 syndrome patients. Of these 18 patients, 15 had arthritis, 14 had myositis and 14 had interstitial lung disease. Only four patients had myositis at disease onset. We describe four unusual patients with Jo-1 syndrome in detail: 1. Long history of seronegative rheumatoid arthritis; 2. Sjögren's syndrome with Ro- and La-antibodies; 3. Scleroderma and bronchial carcinoma with centromere antibodies; 4. Corticoid-sensitive psychosis. Patients with suspected connective tissue disease may be screened for anti-Jo-1 antibodies by ELISA. It detects some patients that are missed by immunodiffusion. Especially lower ELISA titres should be controlled by another method because of the low specificity of the test. The clinical picture is variable. Most patients have features other than myositis at disease onset.
10088761 Provision of primary care by office-based rheumatologists: results from the National Ambul 1999 Mar OBJECTIVE: To determine the extent to which office-based rheumatologists provide primary care to patients without rheumatic diseases or provide principal care to patients with rheumatoid arthritis (RA). METHODS: The National Ambulatory Medical Care Survey was used to determine national probability estimates of the nature and types of conditions treated by office-based rheumatologists in 1991-1995. At each of 1,074 patient visits, the rheumatologists recorded up to 3 diagnoses and 3 patient-reported reasons for the visit, as well as information on the treatments provided at the visit. RESULTS: In only 9.8% of new consultations and 11.9% of return visits was neither a rheumatic disease diagnosis nor a musculoskeletal complaint recorded, indicating that the rheumatologist was likely acting as a primary care provider at a minority of patient visits. Among continuing patients with RA, the patient's primary reason for the visit was something other than a musculoskeletal complaint in only 9.9% of visits, and any nonrheumatic complaint was recorded in 30.4% of visits, indicating that at only some visits was the rheumatologist acting as the principal caregiver. In addition, only 31.1% of visits included the provision of medication for a nonrheumatic condition. CONCLUSION: In 1991-1995, most visits to rheumatologists involved the provision of specialized or consultative care to patients with rheumatic diseases or musculoskeletal complaints, and few visits were made by patients without either indication. Provision of principal care by rheumatologists to patients with RA is not currently widespread.
9214253 Costs, outcomes, and patient satisfaction by provider type for patients with rheumatic and 1997 Jul 1 PURPOSE: To compare the outcomes of care provided by generalists with that provided by specialists for patients with musculoskeletal and rheumatic conditions. DATA SOURCES: English-language studies published between 1986 and April 1996 were identified through a MEDLINE search. STUDY SELECTION: Studies that compared generalists' and specialists' treatment preferences, appropriateness of care, or outcomes with regard to musculoskeletal and rheumatic conditions were examined. DATA EXTRACTION: Studies were reviewed for methodologic rigor and outcomes. DATA SYNTHESIS: Low back pain is treated by many types of providers, without consistent differences in outcomes across provider types. In one study, however, patients were more satisfied with chiropractic care than with care provided by primary care physicians, although the former cost twice as much as the latter. For osteoarthritis of the hip, rheumatologists and primary care providers reported using different therapeutic regimens. For acute mono- and oligoarthritis, rheumatologists performed arthrocentesis more appropriately than nonrheumatologists and produced shorter durations of hospitalization. In the management of gout, rheumatologists used colchicine during the introduction of urate-lowering therapy more appropriately than other providers. In two population-based cohorts of patients with rheumatoid arthritis, patients cared for by rheumatologists were prescribed significantly more disease-modifying agents and had less disability than patients cared for by generalists. CONCLUSIONS: Although empirical data are scant, there seem to be differences between generalists and specialists for a range of outcomes in various musculoskeletal and rheumatic conditions. Studies to data have important methodologic limitations that need to be addressed in future research.
9195528 Work and disability status of persons with fibromyalgia. 1997 Jun OBJECTIVE: To determine the prevalence and determinants of self-reported work disability in persons with fibromyalgia (FM). METHODS: A longitudinal, multicenter survey of 1604 patients with FM from 6 centers with diverse socioeconomic characteristics was begun in 1988. Assessments were by self-report questionnaire and telephone contact, and included work and disability events that occurred before and after 1988. Comparative analyses were performed on the entire data set and, separately, on the Wichita data set. RESULTS: More than 16% of patients reported receiving US Social Security disability (SSD) payments (highest center rate 35.7%; lowest center rate 6.3%) compared to 2.2% of the US population (US Social Security Administration data) and 28.9% of patients with rheumatoid arthritis seen at the Wichita outpatient rheumatology clinic. Overall, 26.5% reported receiving at least one form of disability payment when SSD and other sources of disability payments were considered. In Wichita, less than 25% of SSD awards were made specifically for FM, but after 1988 that figure increased to 46.4%. Work disability was greatest at the San Antonio and Los Angeles centers. Multivariate predictors (correlates) included pain, Health Assessment Questionnaire disability, and unmarried status. In addition, more than 70% of patients reporting being disabled did receive disability payments. On the other hand, 64% reported being able to work all or most days, and more than 70% were employed or were homemakers. CONCLUSION: Although most patients (64%) report being able to work, we found high rates of self-reported work disability awards among persons with FM followed in 6 rheumatology centers. But we also found great variability among centers as to awards and as to self-reported work ability. Center differences in work disability might reflect clinic referral patterns, physician beliefs, or socioeconomic status.
9415630 Variability in cytokine and cell adhesion molecule staining in arthroscopic synovial biops 1997 Dec OBJECTIVE: To investigate the variability in immunostaining for cytokines and cell adhesion molecules using multiple arthroscopically directed synovial biopsies from within a rheumatoid knee joint, quantitated by color video image analysis. METHODS: Needle arthroscopic biopsies were taken from multiple sites (4-7 sites) around a knee joint in 8 patients with rheumatoid arthritis (RA). In 5 patients, immunoperoxidase staining for the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and IL-1beta as well as the IL-1 receptor antagonist protein (IL-1ra) was performed. In 3 patients, immunoperoxidase staining for the cell adhesion molecules E-selectin (CD62E), P-selectin (CD62P), intercellular adhesion molecule 1 (ICAM-1, CD54), and platelet endothelial cell adhesion molecule (PECAM, CD31) was performed. Immunostaining was quantified using color video image analysis. RESULTS: The overall probability of paired biopsies from the same RA knee joint being significantly different from each other due to sampling variation was at most 22% for cytokine staining (usually less than 10%). There were no significant differences between intrabiopsy and interbiopsy variability for cell adhesion molecule staining of the sublining and vessels. CONCLUSION: The variability in cytokine and cell adhesion molecule staining within any single biopsy usually reflects the variability between biopsies taken from different sites in the same rheumatoid joint when the immunostaining is quantified using color video image analysis. Therefore, only a small number of synovial biopsies are required to accurately determine the cytokine and cell adhesion molecule expression in a single joint.
10627722 Surgery in patients with systemic sclerosis of the hand. 1999 Sep Systemic sclerosis of the hand is an uncommon form of arthritis that can cause significant functional loss in the hand. It poses serious problems for the surgeon because of the diminished circulation of the digits. The tightness of the skin and joint stiffness that are characteristic of this condition make restoration of function difficult. Calcinosis, which is common in patients with systemic sclerosis of the hand, can be treated by excision or curettage. Patients with severe deformities of the digits and thumb often require fusions to improve grasp. Joint replacements with implants are not as successful in patients with systemic sclerosis as they are in patients with rheumatoid or degenerative arthritis. There have been recent attempts to improve the circulation to the fingers by sympathectomy or by vein grafts. These techniques, however, provide only temporary improvement and do not prevent or correct the severe digital and thumb deformities associated with this disease.
11431697 Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis an 2001 Jul The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families. We localized the disease gene to 16q12-21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion.
10201651 Are randomized control trial outcomes influenced by the inclusion of a placebo group?: a s 1999 Feb Placebo groups are often included in randomized control trials evaluating drug therapy, yet we know little about the placebo effect. The purpose of our study was to evaluate how the presence of a placebo group in a randomized control trial (RCT) influences the patients' ratings of the efficacy of an active drug therapy and their reporting of its adverse effects. We identified studies published between 1966 and 1994 using MEDLINE. Randomized control trials evaluating acetylsalicylic acid, diclofenac, or indomethacin for the treatment of osteo or rheumatoid arthritis were included in our sample. Two investigators independently extracted data. Fifty-eight treatment arms met our inclusion criteria and were available for analysis. Twenty-five treatment arms evaluated a nonsteroidal antiinflammatory drug (NSAID) in placebo control trials and 33 in comparative trials. Using a logistic regression model to adjust for the differences between the evaluated drugs and between the types of arthritis, we found that patients receiving an NSAID in a placebo control trial were more likely to withdraw due to inefficacy (OR=1.3; 95% CI, 1.0 to 1.6; P=0.04). Using a similar model, withdrawals due to adverse effects were found to be more common when the NSAID was given in trials that did not include a placebo group (OR=1.5; 95% CI, 1.1 to 1.9; P=0.002) as were reports of cutaneous (OR=4.2; 95% CI, 1.7 to 9.9), gastrointestinal (OR=1.6; 95% CI, 1.3 to 2.0), and other types (OR=5.3; 95% CI, 3.8 to 7.4) of adverse effects. Although reports of central nervous system adverse effects were more frequent in the comparative trials, this difference was not significant. Including a placebo group in a RCT changes how patients rate the efficacy and adverse effects of their therapy. Our results highlight the need to consider the placebo effect in the design and analyses of clinical trials.
9920980 Peripheral blood mononuclear cell proliferative response against staphylococcal superantig 1999 Jan It has been recently hypothesized that superantigens play a precipitating or aggravating role in psoriasis. Aside from streptococcal infection, Staphylococcus aureus can be sometimes detected in the tonsils of patients with psoriasis arthropathy (PA), although its significance in the pathogenesis of PA is still unknown. These focal infections are thought to be a possible triggering factor of the arthralgia, as well as the cutaneous manifestations, in PA. In this study, we have investigated the response of peripheral blood mononuclear cells (PBMC) from patients with PA to staphylococcal superantigens and analyzed its association with clinical and laboratory findings. 3H-TdR uptake by PBMC was examined after 7 days' culture with concanavalin A (Con A), staphylococcal enterotoxin A (SEA), SEB and SEC1. Results showed that there was no significant difference in either the unstimulated or Con A-stimulated PBMC response between psoriasis vulgaris patients (PASI score < 10) (n = 15), PA patients (n = 11) and normal controls (n = 19). Among 11 PA patients, 8 patients responded most intensely to SEB, while 2 patients showed the strongest response to SEA, and another responded mainly to SEC1. The PBMC response against SEB in patients with PA (38,715 719 dpm, stimulation index (SI); 50.2 41.4) (mean SD) was significantly higher than that in normal controls (23,708 466 dpm, SI; 30.9 23.8) (p < 0.05), however, the difference between that of patients with PA and psoriasis vulgaris (33,428 467 dpm, SI; 42.8 30.6) did not reach significance. In addition, PBMC from psoriatic patients with a short episode of severe, disabling lumbago, which occured following sudden onset throat soreness, showed a stronger response against SEB (SI; 73.7 39.7), as compared with that of PA patients without such an episode (SI; 42.6 18.1). However this difference did not reach significance. Several immune abnormalities, including positive antinuclear antibodies or rheumatoid factor were observed mainly in the group experiencing such an episode of severe lumbago. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that predominant expression of the T cell receptor (TCR) Vbeta 17 was commonly detected in both synovial tissues and paired peripheral bloods in two cases examined. In one case, Vbeta 12 was preferentially expressed, and in another case, Vbeta 10, 15 and 19 were also strongly expressed in the infiltrating lymphocytes in the synovial tissues. Our data raised the possibility that staphylococcal superantigens may also play an exacerbating role in PA.
11208502 Immunological investigation in children with juvenile chronic arthritis. 2001 Jan BACKGROUND: Immunological investigation is a part of the complex view on a child with juvenile chronic arthritis (JCA). We analyzed the data of a cohort of children with JCA in order to determine the real contribution of this investigation to their diagnosis and therapy. MATERIAL AND METHODS: We included the investigation of humoral immunity and autoantibodies of 78 children with JCA. 18 children completed investigation of both humoral and cellular immunity of paired peripheral blood (PB) and synovial fluid (SF). Humoral immunity consisted from immunoglobulins, complement, circulating immune complexes, rheumatoid factors, soluble HLA I. molecules and antinuclear and antineutrophil cytoplasmic antibodies. Cellular immunity included cytometric studies of CD3, CD4, CD8, CD16/CD56, CD19, CD20, 23, CD3 HLA DR+, CD45 RA, CD45 RO, alpha/beta and gamma/delta T cells. To observe the status of Th1/Th2 balance in children with JCA, the cytokines IL-4, IFN gamma, TNF alpha and IL-6 were measured in the tissue culture of the synovial cells. RESULTS: The parameters of humoral immunity in serum showed wide variability. We could not confirm particular changes specific for the forms or stage of the disease. ANCA were positive in 21 out of 78 children with JCA, 3 times both in PB and SF. More typical pattern could be followed in the comparison of PB and SF, with immunoglobulins and complement always found lower in SF than in PB. The cellular immunity was represented by the activation of lymphocytes mainly in SF, reverse ratio of CD45 RA and RO cells in PB and SF with marked predominance of memory T cells in the joint. High levels of sHLA in SF are the nonspecific marker of activation, the same is true for high levels of TNF alpha and IL 6 in SF cell culture supernatant. CONCLUSION: The described changes in immunological parameters of humoral and cellular immunity are not specific for JCA. In the individual cases they can contribute to the diagnosis and monitoring of the disease. The investigation of sHLA molecules and cytokine profile should be restricted only for research.
9153705 MR imaging of the infrapatellar fat pad of Hoffa. 1997 May The infrapatellar fat pad of Hoffa is an intracapsular structure that is routinely visualized on magnetic resonance images of the knee. Because disease in this region is not uncommon, it is important to be familiar with the various pathologic entities that may occur here. Abnormalities that are intrinsic to this fat pad include Hoffa disease, intracapsular chondroma, localized nodular synovitis, postarthroscopy and postsurgery fibrosis, and shear injury. In addition, the infrapatellar fat pad may be involved secondarily from extrinsic processes, including articular disorders (eg, joint effusion, intraarticular bodies, meniscal cyst, ganglion cyst, cyclops lesion), synovial abnormalities (eg, pigmented villonodular synovitis; hemophilia; synovial hemangioma; primary synovial chondromatosis; chondrosarcoma; lipoma arborescens; rheumatoid, seronegative, and septic arthritis; arthritis associated with inflammatory intestinal disorders; synovitis associated with primary osteoarthritis), and anterior extracapsular abnormalities. The approach to pathologic processes involving the infrapatellar fat pad of Hoffa is simplified when one is familiar with regional anatomy and possible differential diagnostic considerations.
11500467 Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the ra 2001 Sep Peptidoglycan polysaccharide (PG-PS) is a primary structural component of bacterial cell walls and causes rheumatoid-like arthritis in rats. Recently, glycine has been shown to be a potential immunomodulator; therefore, the purpose of this study was to determine if glycine would be protective in a PG-PS model of arthritis in vivo. In rats injected with PG-PS intra-articularly, ankle swelling increased 21% in 24 to 48 h and recovered in about 2 weeks. Three days prior to reactivation with PG-PS given intravenously (i.v.), rats were divided into two groups and fed a glycine-containing or nitrogen-balanced control diet. After i.v. PG-PS treatment joint swelling increased 2.1 +/- 0.3 mm in controls but only 1.0 +/- 0.2 mm in rats fed glycine. Infiltration of inflammatory cells, edema, and synovial hyperplasia in the joint were significantly attenuated by dietary glycine. Tumor necrosis factor alpha (TNF-alpha) mRNA was detected in ankle homogenates from rats fed the control diet but not in ankles from rats fed glycine. Moreover, intracellular calcium was increased significantly in splenic macrophages treated with PG-PS; however, glycine blunted the increase about 50%. The inhibitory effect of glycine was reversed by low concentrations of strychnine or chloride-free buffer, and it increased radiolabeled chloride influx nearly fourfold, an effect also inhibited by strychnine. In isolated splenic macrophages, glycine blunted translocation of the p65 subunit of NF-kappaB into the nucleus, superoxide generation, and TNF-alpha production caused by PG-PS. Further, mRNA for the beta subunit of the glycine receptor was detected in splenic macrophages. This work supports the hypothesis that glycine prevents reactive arthritis by blunting cytokine release from macrophages by increasing chloride influx via a glycine-gated chloride channel.
10332212 [A case of seronegative spondylarthropathy with iritis and retroperitoneal fibrosis]. 1999 Feb In 1985 a 41-year old male visited a local hospital because of congestion in the bulbar conjunctiva, which was diagnosed as iritis. In August 1990, right coxalgia and arthralgia of metatarsophalangeal joints appeared, with recurrence of iritis. In October, stiffness in the hands and arthralgia of proximal interphalangeal joints also started. In July 1991, the right coxalgia worsened, resulting in walking difficulty. He was admitted to the Kitasato University Hospital. He presented with bilateral iritis, polyarthritis with limited ranges of motion and sacroilitis. The Schober's test was positive at 3 cm. Serological tests for rheumatoid factor and HLA-B 27 were negative. Abdominal computer tomographic scan revealed low density lesion around the aorta. PSL 10 mg was initiated, and iritis and arthritis remitted. Progression of the periaortic lesion was not observed during the subsequent 5 years. In this case, iritis preceded limited ranges of motion in the vertebrae and sacroilitis. From these findings, seronegative spondylarthropathy with peripheral arthritis was diagnosed. The periaortic lesion seen in this case probably corresponds to chronic periaortitis recently reported as a subset of idiopathic retroperitoneal fibrosis. The two lesions observed in the present case may be interpreted as caused by inflammation of the connective tissue initially either at the vertebrae or around the aorta, which had advanced to involve the other lesion.
9575496 Matrix metalloproteinases and TIMPs: properties and implications for the rheumatic disease 1998 Mar The matrix metalloproteinases (MMPs) are a unique family of metalloenzymes, which, once activated, can destroy all the components of cartilage. MMPs are found in resorbing cartilage, bone, rheumatoid and osteoarthritic synovial fluid, and adjacent soft tissues. The active enzymes are all inhibited by tissue inhibitors of metalloproteinases (TIMPs). The relative amounts of active MMPs and TIMPs are important in determining whether cartilage is broken down in joint diseases. Conventional treatments for arthritis do little to affect the underlying joint destruction, but new drugs are now available that can specifically block active MMPs. These potent inhibitors prevent the destruction of cartilage both in vitro and in animal models of arthritis. Future trials in patients will test their effectiveness in the prevention of cartilage destruction.
9580179 [Whipple's disease: early diagnosis through articular disease and hyperpigmentation]. 1998 Jan We present a new case of Whipple's disease. The patient have a clinical history of steatorrhea and diarrhea of various years of evolution with hyperpigmentation of skin and mucosae and migratory polyarthralgias with inflammatory sings. The biochemicals analysis for rheumatoid and endocrinological diseases were negatives. A endoscopically yeyunal biopsy was performed and the diagnosis of Whipple's disease was made. We comment this clinical presentation of Whipple's disease with a seronegative inflammatory rheumatological disease. The differential diagnosis with seronegative arthritis was emphasized.
9269151 Radiolunate fusion. The forgotten partial arthrodesis. 1997 Aug Radiolunate fusion has been used successfully in the treatment of rheumatoid ulnar translation of the carpus and degenerative radiolunate arthritis. Fusing the lunate to the radius places the keystone of the carpus in an aligned and stable position. The use of radiolunate fusion has been introduced here for other treatment challenges including traumatic ulnar translation of the carpus, dynamic midcarpal instability, volar and static intercalated segment instability. Pain relief was excellent and preoperative range of motion was maintained with radiolunate fusion.
10792392 Fine specificity of autoantibodies to calreticulin: epitope mapping and characterization. 2000 May Extracellular calreticulin (CRT) as well as anti-CRT antibodies have been reported in patients with various autoimmune disorders and CRT has been implicated in 'epitope spreading' to other autoantigens such as the Ro/SS-A complex. In addition, antibodies against parasite forms of the endoplasmic reticulum chaperone, CRT, have been found in patients suffering from onchocerciasis and schistosomiasis. In this study, we screened sera for anti-CRT antibodies from patients with active and inactive systemic lupus ertythematosus (SLE) and primary or secondary Sjögren's syndrome. Approximately 40% of all SLE patients were positive for anti-CRT antibodies. The antigenic regions of CRT were determined using full length CRT and fragments of CRT prepared in yeast and Escherichia coli, respectively. Synthetic 15mer peptides corresponding to the major autoantigenic region of CRT (amino acids 1-289), each one overlapping by 12 amino acids, were used to map the B cell epitopes on the CRT protein recognized by autoimmune sera. Major antigenic epitopes were found to be associated with the N-terminal half of the protein in 69% of the SLE sera from active disease patients, while the C-domain was not antigenic. Major epitopes were found to be reactive with antibodies in sera from SLE patients with both active and inactive disease, spanning different regions of the N and P-domains. Sera from both healthy and disease controls and primary Sjögren's syndrome patients were non-reactive to these sequences. Limited proteolysis of CRT with two major leucocyte serine proteases, elastase and cathepsin G, demonstrated that an N-terminal region of CRT is resistant to digestion. Interestingly, some of the epitopes with the highest reactivity belong to the fragments of the protein which bind to C1q and inhibit complement activation. Whether C1q association with CRT is a pathological or protective interaction between these two proteins is currently under investigation.
10736101 Enhanced sialyltransferase activity in B lymphocytes from patients with primary Sjögren's 2000 Mar Despite the indisputable role of immunoglobulin (Ig)A in the pathogenesis of primary Sjögren syndrome (pSS), the causative abnormality remains largely unknown. As an extension of our report that IgA is oversialylated in this disease, the thrust of the present study was to measure the sialyltransferase (ST) activity in B lymphocytes. ST containing lysates of B cells from 17 pSS patients and 10 controls, were obtained using a combination of detergents, and incubated with affinity purified IgA that had been previously desialylated. The deposition of cytidine 5' monophosphate sialic acid (SA) by ST from B cells onto IgA was detected by two ELISA based upon the use of biotinylated lectins (Sambucus nigra agglutinin which is specific for alpha2-6 SA and Maackia amurensis which is specific for alpha2-3 SA). In parallel, the amount of SA on IgA from ten of the 17 patients and eight of the 10 controls was assayed using the same method. An excess of alpha2-3 and alpha2-6 SA on IgA was found in those patients with excessive activity of alpha2-3 and alpha2-6 ST. Thus, IgA hypersialylation in pSS patients may result from undue activity of ST.
9888423 Regulation of human leukocyte antigen expression in human conjunctival epithelium. 1999 Jan PURPOSE: To demonstrate that interferon-gamma (IFN-gamma) is the key cytokine responsible for the upregulation of HLA-DR antigen in conjunctival epithelial cells of Sjogren syndrome (SS) patients. METHODS: Flow cytometry of conjunctival epithelial cells from SS and non-SS dry eye patients was performed for the quantification of HLA-DR surface expression. With a conjunctival epithelial cell line (ChWK), HLA-DR regulation by various cytokines was evaluated, and confocal immunocytochemical and western blot analyses were performed to evaluate the activation of nuclear factorkappa B (NF-kappaB) and signal transducers and activators of transcription 1 and 3 (STAT1 and STAT3, respectively). RESULTS: HLA-DR expression was upregulated in conjunctival epithelial cells of SS patients but not in non-SS dry eye patient or healthy control subject. IFN-gamma was the only cytokine that effectively upregulated HLA-DR expression in ChWK, which was synergistically enhanced by tumor necrosis factor-alpha (TNF-alpha). IFN-gamma induced the nuclear translocation of NF-kappaB, but did not activate STAT1 or STAT3 in ChWK. CONCLUSIONS: Upregulation of HLA-DR antigen in the conjunctival epithelium of SS patients may be regulated by IFN-gamma through the activation of NF-kappaB.
9796339 [Association of extrahepatic autoimmune diseases in primary biliary cirrhosis--clinical st 1998 Oct Abnormality of humoral and cellular immune functions and the association of autoimmune diseases are frequently observed in primary biliary cirrhosis (PBC). The prevalence of autoimmune diseases was studied in 97 Japanese patients with PBC. Sjögren's syndrome was diagnosed in 33 percent of these patients, arthritis in 22 percent, scleroderma in 11 percent, CREST syndrome in 4 percent, Raynaud's phenomenon in 8 percent, autoimmune thyroiditis in 3 percent, respectively. Fifty-five percent of the patients had at least one autoimmune disease and 19 percent had two or more such disorders. In this study, the prevalence of associated autoimmune diseases was somewhat low compared to that of European and American studies. Geographical variations, however, might exist in the prevalence of autoimmune associations, and the frequent occurrence of coexisting autoimmune diseases suggests an autoimmune pathogenesis in PBC.