Browse

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

ID PMID Title PublicationDate abstract
8817167 Epitope mapping of the Ro/SSA60KD autoantigen reveals disease-specific antibody-binding pr 1996 Jun Anti-Ro60KD autoantibodies are commonly found in sera from patients with primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). In order to identify the epitopes of this autoantigen, 22-mer, synthetic peptides overlapping by eight residues, and covering the entire sequence of the Ro60KD autoantigen were prepared. Three groups of sera were evaluated according to their autoantibody specificites. The first group consisted of monospecific anti Ro60KD sera from four patients with SLE and one with SS, the second one was composed of anti-Ro60KD+anti-La(SSB)-positive sera from four patients with SS and the third group included three normal sera and one anti Ro52KD serum. It was found that sera from SLE patients interact with a common antigenic site spanning the sequence TKYKQRNGWSHKDLLRSHLKP (169-190) of the Ro60KD protein. On the other hand, sera from SS patients recognise the ELYKEKALSVETEKLLKYLEAV (211-232) region of this autoantigen. Determination of the minimal required peptide length for optimal antibody recognition showed that the defined epitopes can be shortened to the NGWSHKDLLR (175-184) and KALSVETEKLLKYLEAV (216-232) sequences respectively. Inhibition experiments using the Ro60KD antigen and soluble peptides corresponding to the 175-184 and 216-232 segments further confirmed the specific antibody binding. These results, although only a small number of sera were used, indicate that the Ro60KD autoantigen, which is not characterized by disease specificity, contains two discrete epitopes specifically recognized from SLE and SS patient sera. Finally, the sequence similarity of the NGWSHKDLLR (175-184) epitope with some of the HLA haplotypes, associated with anti-Ro response, deserves to be noted.
8624627 A case of primary Sjögren's syndrome, complicated by cryoglobulinaemic glomerulonephritis 1996 Jan Primary Sjögren's syndrome (SS1) complicated by glomerulonephritis is rare and is usually associated with the presence of cryoglobulins. Cryoglobulinaemic glomerulonephritis as described in type II essential mixed cryoglobulinaemia, characterized by the presence of deposits of cryoglobgulins within the glomerular capillary lumen, occurring in SS1 has previously been reported only once in the literature. Our case was also complicated by pleural and pericardial effusions. We discuss the treatment options available for the renal lesion.
8587757 Value of quantitative salivary gland scintigraphy in the early stage of Sjögren's syndrom 1995 Nov The aim of this study was to test the impact of quantitative salivary gland scintigraphy in patients with suspected Sjögren's syndrome. Thirteen patients with suspected Sjögren's syndrome were investigated. During clinical work-up, three had severe and four had mild Sjögren's syndrome, while six were normal. Quantitative salivary gland scintigraphy was performed using a standardized method. The normal data-base consisted of 172 patients without any evidence of salivary gland malfunction. Visual and quantitative comparisons of the patients' scintigrams were made. In the patients with severe Sjögren's syndrome, uptake was 0.10 +/- 0.04% and 0.09 +/- 0.03% in the parotid and submandibular glands respectively, confirming the visual diagnosis. In the patients without Sjögren's syndrome, concordance between the visual and quantitative evaluations could also be shown. In contrast, among the patients with mild Sjögren's syndrome, uptake was diminished (P < 0.05), amounting to 0.21 +/- 0.05% and 0.16 +/- 0.02% in the parotid and submandibular glands respectively, while visual analysis indicated normal parenchymatous function. In conclusion, quantitative salivary gland scintigraphy is essential for the reliable detection of parenchymatous malfunction at an early stage of Sjögren's syndrome, which may be missed by visual analysis alone.
8531358 [Expression of sequences homologous to HTLV-I pXIV gene in the labial salivary glands of J 1995 Oct To address the question of whether the human T cell leukemia virus type I (HTLV-I) gene is associated with the etiology of Sjögren's syndrome (SS), RNA expression of HTLV-I gag, pol, env, and tax genes in labial salivary glands (LSGs) from SS patients who were seronegative for antibodies to HTLV-I was examined using RT-PCR method. The HTLV-I tax gene, but not the HTLV-I gag, pol, or env genes, was detected in LSG samples from 4 of 14 patients (29%). The nucleotide sequences of the HTLV-I pXIV region in these 4 patients' LSGs showed 100% homology to the HTLV-I pXIV gene from the MT-2 cell line. In conclusion, these findings suggest that products encoding sequences homologous to the HTLV-I pXIV gene in SS patients' LSGs might be candidates for self-antigen and/or lead to activation of autoreactive T lymphocytes through trans-acting transcriptional activation.
7586784 Primary Sjögren's syndrome and primary biliary cirrhosis: differences and similarities in 1995 Jul Sera from 61 patients with primary biliary cirrhosis (PBC) and 23 patients with primary Sjögren's syndrome (pSS) were tested for the presence of autoantibodies to 15 different antigens (PDH, RNP, SS-A, SS-B, Sm, Scl-70, H2AH2B, Jo-1, collagen-type I, GBM, GM <--> 1, Sulf, GD1b, MPO, PR3). Patients with pSS had significantly (p < 0.01) higher frequencies of antibodies to SS-A, SS-B and RNP (78%, 52%, 22% vs 29%, 20%, 5%, respectively) when compared to patients with PBC. On the other hand, patients with PBC had significantly (p < 0.01) higher frequencies of antibodies to PDH, Sm, Jo-1, collagen and MPO (80%, 34%, 26%, 52%, 67% vs 13%, 9%, 13%, 13%, 9%, respectively) as compared with patients with pSS. For all the other autoantibodies, no significant differences were found between PBS and pSS patients. These data on the similarities in autoimmunity between two diseases with different clinical presentations shed more light on the mosaic of autoimmunity.
7955565 IgG subclasses of anti-SS-A/Ro in patients with primary Sjögren's syndrome. 1994 Dec Patients with primary Sjögren's syndrome mostly have high levels of polyclonal IgG, and subclass analysis frequently shows selective IgG1 increase with low IgG2. In this study IgG subclass profiles of anti-SS-A/Ro were examined using ELISA technique. Results show marked IgG subclass restriction of anti-SS-A/Ro autoantibodies (high IgG1/low IgG2). Comparison of the levels of specific IgG subclass autoantibodies with total levels of the corresponding subclass disclosed divergence regarding IgG2, IgG3, and IgG4, but not IgG1. Thus, total levels of IgG1 paralleled the levels of IgG1 anti-SS-A antibodies. Specific autoantibodies of IgG2 subclass could not be detected despite low or normal levels of total IgG2. Elevated levels of specific IgG3 and IgG4 antibodies were seen, although total levels of the corresponding subclasses were within normal limits. These findings may possibly be of relevance with regard to antigen-driven activation of autoantibody-producing plasma cell clones.
8057125 Peripheral neuropathy associated with primary Sjögren's syndrome. 1994 Aug Clinical and electrophysiological signs of peripheral neuropathy were found in 10 of 46 patients (21.7%) with primary Sjögren's syndrome, symmetric polyneuropathy in seven (mainly sensory in five, mainly autonomic in two), sensory neuronopathy in two patients, and mononeuropathy multiplex in one patient. Peripheral neuropathy was the presenting manifestation in five patients (10.9%). Onset of the disease after 50 years was significantly more common in the polyneuropathy group (six of seven) than in non-neuropathic patients with primary Sjögren's syndrome (14 of 36; p = 0.034). No other difference in clinical or laboratory variables between neuropathic and non-neuropathic patients with primary Sjogren's syndrome was found. Neurophysiological study showed variable findings predominantly suggesting an axonopathy. Nerve biopsy showed moderate remyelination and regeneration in four patients, and fibre loss, mainly of large size, in three. Necrotising vasculitis was not seen but alterations of the endoneurial microvessels were prominent.
8056476 Prevalence of eyelid dermatitis in primary Sjögren's syndrome. 1994 Jun BACKGROUND: The eyelid dermatitis seen in elderly patients is a relatively heterogenous and troublesome disease. Most cases seem to be idiopathic and show resistance to standard dermatologic therapy. METHODS: Fifty-two patients with primary definite Sjögren's syndrome (4 men, 48 women, mean age 54 years) were enrolled in this study, and the prevalence of eyelid dermatitis was investigated. Diagnostic criteria for Sjögren's syndrome were based on the criteria proposed by the Japanese Ministry of Health and Welfare. Patch test was performed using ICDRG-European standard allergens and/or eye drops, hair dye, and cosmetics. RESULTS: Of the 52 patients, 22 showed eyelid dermatitis. These changes were much more frequent in elderly patients and showed a good correlation with the presence of ocular dry sensation. No significant difference was observed in clinical and other laboratory findings between patients with or without eyelid dermatitis. Although 8 of the 13 patients showed positive patch test reaction to various allergens, no close relationship existed between the use of a suspected substance and the onset or severity of eyelid dermatitis. CONCLUSIONS: These results suggest that the presence of rubbing dermatitis of the eyelid may be one of the cutaneous manifestations of Sjögren's syndrome.
8165437 Magnetic resonance imaging of the parotid glands and lip biopsy in the evaluation of xeros 1994 Magnetic Resonance Imaging (MRI) of the parotid glands was performed in 23 patients with dry mouth. Each patient underwent lip salivary gland (LSG) biopsy and complete clinical and immunological assessment. MRI showed a quite specific nodular pattern in the parotid glands of patients with Sjögren's syndrome (SS), especially those with severe histologic abnormalities in LSG. However no significant correlation could be detected between MRI score and both LSG biopsy class and immunological abnormalities. MRI of the parotid glands can be regarded as a useful noninvasive procedure with high positive predictive value for the evaluation of the salivary component in SS.
8030545 Murine models of Sjögren's syndrome. 1994 Autoimmune MRL/lpr, MRL/+, and NZB/W mice all develop lacrimal gland inflammatory lesions, which consist of focal mononuclear inflammatory cell infiltrates. Each strain has a different immunocytochemical profile, which appears to be related to the underlying immunologic defects present in that mouse. The appearance of these lesions parallels the evolution of the systemic autoimmune disease. The lesions are dynamic over time with the early appearance of CD4+ T cells (helper T cells) for each strain. Subsequently, there is an accumulation of B cells over time in MRL/+ and NZB/W mice. In the two more rapidly evolving mouse models, MRL/lpr and NZB/W, there is a progressive decline in the percentage of CD8+ cells. Conversely, in the slowly evolving MRL/+ lacrimal gland lesions, there is a persistent and unchanging percentage of CD8+ T cells (suppressor/cytotoxic T cells). Autoimmune mice provide models for the human disorder Sjögren's syndrome and a mechanism for better understanding the immunopathogenesis of autoimmune lacrimal gland disease.
8464611 Mucin-containing lozenges in the treatment of intraoral problems associated with Sjögren' 1993 Apr Irreversible hyposalivation is a common sequela of Sjögren's syndrome and may lead to a decreased quality of the patient's life. The aim of this study was to evaluate the efficacy and therapeutic value of mucin-containing lozenges in reducing patients' complaints of hyposalivation. In a double-blind crossover trial in 42 patients with Sjögren's syndrome, the efficacy and therapeutic value of both a mucin-containing and placebo lozenge were assessed by means of self-administered questionnaires, which had to be completed before and after the use of each type of lozenge for a period of 2 weeks. Seventy-six percent of the patients preferred the mucin lozenge, 10% preferred the placebo, and 14% had no preference. In reducing patients' complaints, sucking the mucin lozenge resulted in a larger improvement of the total pattern of complaints and the sensation of oral dryness, and in a longer moistening of the oral cavity than the placebo. Oral functioning was improved after the use of the placebo, and the patients reported the taste of the placebo to be better than the mucin lozenge. From the responses it was concluded that the use of the mucin lozenges can be recommended in the treatment of oral symptoms of xerostomia.
7569597 [Rheumatic involvement in Hansen's disease]. 1995 Mar The classical articular manifestations of Hansen's disease are the neurogenic or Charcot's arthropathy, osteitis and specific or non specific osteoarthritis. However, inflammatory mechanisms have been associated to arthritic episodes in leprosy patients, leading to rheumatoid-like picture as suggested by clinical, biopsy and laboratorial data. The extra-articular manifestations also mimicry those of some connective tissue diseases. The differencial diagnosis between rheumatic syndromes and hanseniasis is important for as early indentification of hanseniasis and prevention of severe sequelae and transmission.
8835245 Subjective and clinical oral symptoms in patients with primary Sjögren's syndrome. 1995 Nov OBJECTIVE: To study subjective and clinical oral symptoms and their possible correlations in patients with primary Sjögren's syndrome (1 degree SS). METHODS: In 40 cases fulfilling the Copenhagen as well as the San Diego criteria for 1 degree SS, different subjective symptoms were registered during an interview and by using a questionnaire and visual analogue scales (VAS). A clinical examination was performed to record the salivary parameters, dental status, candidosis, other mucosal lesions, and oral dysfunction. RESULTS: Subjectively, dryness was reported by 98%, soreness by 63%, angular lesions by 70%, and mucosal ulcerations by 40% of the patients. Frequent carious lesions were a major subjective complaint. Clinically, the dental status did not differ from that of the Swedish general population except for a somewhat increased number of filled and decayed surfaces, here 3.5 per tooth on the average. Candidosis was present in a total of 30 patients (75%), and angular cheilitis in 14 (35%). Intraoral cultivation of Candida did not correlate with the clinical findings. Very high counts of lactobacilli and mutans streptococci were found in 77% and 47% of the patients, respectively. Decreased unstimulated saliva was significantly correlated to the subjective degree of dryness, while decreased stimulated saliva could be correlated to increased focus scores in labial salivary gland biopsies and to the presence of mucosal candidosis. Statistically significant correlations were also noted between focus scores and the grades of subjective and clinical dryness. Lichenoid lesions were seen in 18% and oral dysfunction in 55% of the 1 degree SS patients. CONCLUSION: The impaired salivary function in 1 degree SS can be related to several subjective complaints and clinical disorders. Increased attention to and treatment of the symptoms noted is a necessity for the early diagnosis and relief of oral distress.
8213004 Autoimmune haemolytic anaemia, Sjögren's syndrome and idiopathic thrombocytopenic purpura 1993 A unique occurrence of sarcoidosis autoimmune haemolytic anaemia (AIHA), Sjögren's syndrome and idiopathic thrombocytopenic purpura (ITP) in the same patient is reported. Although the occurrence of autoimmune disease with sarcoidosis is well known, a case in which several of these diseases coexist with sarcoidosis is rare. We present a man with longstanding sarcoidosis who developed AIHA. Sjögren's syndrome and ITP. This case report seems to be the first case in which three autoimmune diseases were accompanied by sarcoidosis in 1 patient.
1484932 Haematological manifestations of primary Sjögren's syndrome: a clinicopathological study. 1992 Jul Clinically significant cytopenias are thought to be uncommon in primary Sjögren's syndrome: only a few cases have been reported in the literature. Over a 3-year period we identified haematological abnormalities in 11 of 27 patients with Sjögren's syndrome. Six patients had a positive direct antiglobulin test, including one patient with all the features of autoimmune haemolytic anaemia and two others with some features of this condition. Four patients had immune thrombocytopenia and two patients had myelodysplastic syndrome. Neutropenia was noted in two patients, one patient had aplastic anaemia and one had pure red cell aplasia. Haematological disorders were found to be common in patients with Sjögren's syndrome (40 per cent). Accordingly, we suggest that patients with immune cytopenia(s) should be screened for Sjögren's syndrome using sensitive assays for anti-SS.A and anti-SS.B antibodies, and that patients with Sjögren's syndrome should be periodically monitored, with a full blood count to rule out any haematological abnormality.
1603204 Autoantibodies and their target antigens in Sjögren's syndrome. 1992 Apr The subject of this review is the humoral autoimmune response in Sjögren's syndrome. Autoantibodies in this disease are primarily directed against the Ro/SS-A and La/SS-B autoantigens and against IgG (rheumatoid factor). The Ro/SS-A and La/SS-B autoantigens consist of a number of antigenic proteins coupled to small RNA molecules. These RNA-protein particles are present in all human cells and are strongly conserved throughout various species. Anti-Ro/SS-A and anti-La/SS-B autoantibodies can be detected using counter-immunoelectrophoresis, immunoblotting technique, ELISA or RNA precipitation assays. The preferred method of screening for anti-Ro/SS-A antibodies in human sera is counter-immunoelectrophoresis; anti-La/SS-B antibodies are best detected with the immunoblotting technique. Anti-Ro/SS-A antibodies are found in 60% of patients with Sjögren's syndrome, but are not specific markers for this disease. Anti-La/SS-B antibodies are present in approximately 40% of patients with Sjögren's syndrome; the only other disease where the antibody has been detected is systemic lupus erythematosus (15% positive). The origin and possible pathogenetic role of autoantibodies in Sjögren's syndrome is still unclear. Our view is that the current evidence supports a mechanism whereby autoantibodies are the product of an oligoclonal B-cell proliferation. The only instance where autoantibodies probably play a direct pathogenetic role is the occurrence of congenital heart block in the offspring of anti-Ro/SS-A and anti-La/SS-B positive mothers.
8882037 Reduced serum creatine kinase activity in inflammatory rheumatic diseases. 1996 Feb OBJECTIVE: To determine if serum CK activity is reduced in inflammatory rheumatic diseases and to evaluate whether this phenomenon is linked to disease activity or steroid therapy. METHODS: Serum CK activity was measured in patients with systemic lupus erythematosus (SLE, n = 52), rheumatoid arthritis (RA, n = 80), ankylosing spondylitis (AS, n = 82), spondyloarthropathies other than AS (SpA, n = 22), and a miscellaneous group (MI, n = 27), and in 103 control patients with noninflammatory arthropathies (NIA). Laboratory variables of inflammatory activity such as ESR, CRP, platelet count, and hemoglobin (and anti-DNA antibodies and complement levels in SLE) were measured at the same time. Daily dose of steroids was also evaluated. RESULTS: Serum CK activity was significantly reduced in SLE (mean +/- SD: 49 +/- 41 IU/l), RA (68 +/- 41 IU/l), SpA (88 +/- 53 IU/l), and MI (75 +/- 32 IU/l) compared to controls (111 +/- 38 IU/l) (p = 0.002 for SpA and p < 0.001 for the other groups). No differences in CK values were observed between AS and controls, although AS patients with peripheral arthritis had lower serum CK activity than those without (80 +/- 32 vs 121 +/- 62 IU/l, respectively, p < 0.05. ESR, CRP, and platelets correlated inversely with CK values in RA, AS, and MI. In the SpA group only ESR correlated inversely with CK. In SLE, a positive correlation was found between CK values and CH50 and a negative one with anti-DNA levels. Patients taking steroids had significantly lower CK activity than those without corticotherapy. However, multivariate analysis showed that only inflammatory activity and no steroids had an effect in reducing CK activity. CONCLUSION: Serum CK activity is significantly reduced in several inflammatory rheumatic diseases. Inflammatory activity seems to play the major role in this phenomenon.
17590600 Evaluation of anti-ds DNA antibody measurement by using commercial kits for use in a clini 1995 Jul Three hundred and seventy-six consecutive antinuclear antibody-positive sera were tested for anti-ds DNA antibody by using three commercial kits which use 125 I recombinant DNA (radioimmunoassay), highly purified calf thymus DNA (enzyme linked immunosorbent assay) and Crithidia lucilliae (immunofluorescence assay) as substrates. All patients' sera, after reviewing medical records, were classified into three broad groups: Group I (systemic lupus erythematosus), Group II (rheumatic diseases and rheumatoid arthritis), and Group III (nonspecific ANA antibody test positive). A sensitivity, specificity, positive predictive test value and negative predictive test value for Group I against Group II-III (generally these two groups of sera should not show any anti-ds DNA antibody) combined showed for Crithidia lucilliae (IF assay) 58.8%, 93.6%, 82% and 82%, for 125 I recombinant DNA (RIA) assay, 75.8%, 94%, 86.2% and 88.7% and calf thymus highly purified DNA (ELISA) assay using positive cut-off value >100 U/mL, 97.5%, 35%, 42.9% and 24%. The 125 I recombinant DNA (RIA) assay based on the principle of the Farr technique, which is still considered to be the gold standard for anti-ds DNA antibody detection, showed the best specificity and sensitivity among all three methods tested in this study.
8702439 Detection of autoantibodies to nucleolar transcription factor NOR 90/hUBF in sera of patie 1996 Aug OBJECTIVE: We attempted to clarify the clinical characteristics of Japanese patients with autoantibodies to nucleolar transcription factor NOR 90/hUBF (anti-NOR 90) and to analyze the autoantigenic epitopes recognized by anti-NOR 90. METHODS: Ninety-one patient sera containing anti-nucleolar antibodies (ANoA) by indirect immunofluorescence were collected. Immunoblottings were performed using recombinant fusion proteins expressed from several cloned complementary DNA (cDNA) encoding the NOR 90/hUBF autoantigen. RESULTS: Anti-NOR 90 were detected in sera from 9 (9.9%) of 91 patients with ANoA. Seven of these patients were diagnosed as having Sjögren's syndrome, 4 had concomitant rheumatoid arthritis, 1 had concomitant systemic sclerosis (SSc), and 2 had SSc alone. All 9 sera were reactive with more than 2 recombinant fusion proteins from cDNA encoding separate regions on the hUBF polypeptide. CONCLUSION: The results suggest that while anti-NOR 90 antibodies are rare, they are associated with Sjögren's syndrome in Japanese patients, and that autoimmunity is targeted toward at least 2 separate regions (amino acids 89-310 and 310-633) of the hUBF polypeptide.
8648493 Development of a musculoskeletal extremity health status instrument: the Musculoskeletal F 1996 Mar Despite an increasing reliance on the use of health status measures to assess and evaluate medical care, no single instrument is currently available for use with the broad range of patients with musculoskeletal disorders of the extremities that is commonly seen in clinical practice. In this paper, we report on the development of the Musculoskeletal Function Assessment instrument, a 100-item self reported health status instrument that is designed to meet this need. The instrument was developed in two phases. During the first phase, items were selected on the basis of interviews with 135 patients and 12 clinicians and from reviews of existing health status instruments. The items then were grouped into categories. During the second phase, the instrument was tested for reliability and content validity using a sample of 327 patients with one of five musculoskeletal disorders of the upper and lower extremities (fractures, soft-tissue injuries, repetitive motion disorders, osteoarthritis, and rheumatoid arthritis). The patients were selected from both community and academic sites. Content validity also was demonstrated, based on a review of item selection procedures, expert opinion, and the distribution of scores on the instrument.