Browse

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

ID PMID Title PublicationDate abstract
10929443 [Guideline for the joint swelling symptom--primary physician problem management and referr 2000 Jun The guideline "Joint Swelling" is addressed to primary care physicians--general practitioners, internists or orthopedists without special experience in rheumatology. It provides a framework for interviewing patients, as well as for physical, laboratory and imaging examinations and for selection of treatment appropriate to the level of primary care. Situations which call for urgent evaluation and criteria for referral to rheumatologists are described. The appendix contains comments on signs and symptoms to differentiate arthralgia from joint swelling and on the diagnostic value of a history of joint swelling without confirmation by the physician. Further recommendations for the evaluation of patient history and physical and technical examinations are given in a tabular form. The significance of laboratory and imaging procedures is discussed.
9724775 New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study 1998 Sep 1 Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). Its genetic component has been suggested by familial aggregation (lambdas = 5), twin studies, and segregation analysis. HLA, which is the only susceptibility locus known, has been estimated to account for one-third of this component. The aim of this paper was to identify new RA loci. A genome scan was performed with 114 European Caucasian RA sib pairs from 97 nuclear families. Linkage was significant only for HLA (P < 2.5.10(-5)) and nominal for 19 markers in 14 other regions (P < 0.05). Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci. The first two of these candidate regions, defined in the RA genome scan by the markers D18S68-D18S61-D18S469 (18q22-23) and D3S1267 (3q13), respectively, were studied in 194 additional RA sib pairs from 164 nuclear families. Support for linkage to chromosome 3 only was extended significantly (P = 0.002). The analysis of all 261 families provided a linkage evidence of P = 0. 001 and suggested an interaction between this putative RA locus and HLA. This locus could account for 16% of the genetic component of RA. Candidate genes include those coding for CD80 and CD86, molecules involved in antigen-specific T cell recognition. In conclusion, this first genome scan in RA Caucasian families revealed 14 candidate regions, one of which was supported further by the study of a second set of families.
11562285 Vitamin D analogs: mechanism of action and therapeutic applications. 2001 Nov The physiological VDR ligand, 1 alpha,25-dihydroxyvitamin D3, acts upon a wide variety of tissues and cells, both related to and unrelated to calcium and phosphate homeostasis. The noncalcemic actions of natural and synthetic VDR ligands are exemplified by their potent anti-proliferative, prodifferentiative and immunomodulatory activities. As a result, a VDR ligand is an approved drug for the topical treatment of psoriasis. A plethora of actions of 1 alpha,25-dihydroxyvitamin D3 in various systems have suggested wide clinical applications of VDR ligands in such diverse disease states as inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, photoaging and skin rejuvenation), osteoporosis, cancers (breast, prostate, colon, leukemia and myelodysplastic syndrome) and autoimmune diseases (multiple sclerosis, type I diabetes and systemic lupus erythematosus). VDR ligands have shown therapeutic potential in limited human clinical trials as well as in animal models of these diseases. Some of the VDR ligands have shown not only potent preventive but also therapeutic anabolic activities in animal models of osteoporosis. However, the use of VDR in above mentioned indications as well as in oral therapy for psoriasis and even topical therapy for severe psoriasis is hampered by its associated toxicity, namely hypercalcemia. New VDR ligands have been synthesized which exhibit greater specificity by retaining desirable properties, but with reduced calcemic potential. The discovery of novel vitamin D3 analogs along with an increased understanding of the biological functions and mechanisms of action of VDR are likely to result in improved treatments for responsive indications.
9418636 Acute attenuation of the extensor pollicis longus tendon. A case report. 1997 Dec The current understanding of tendon biomechanics indicates that indirect injury to the tendon midsubstance requires the presence of preexisting disease during mechanical overload. This belief has been substantiated by the association of extensor pollicis longus rupture with chronic tenosynovitis caused by repetitive activity, inflammatory conditions such as rheumatoid arthritis, and minimally displaced distal radius fractures. This case of acute, traumatic, intratendinous attenuation of the extensor pollicis longus tendon offers a contradiction to the view that midsubstance tendon failure requires preexisting disease.
9506576 Possible correction of abnormal rheumatoid arthritis synovial cell function by jun D trans 1998 Mar OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints, and excessive proliferation of and proinflammatory cytokine and collagenase production by synovial cells are a principal cause of joint destruction. Recent studies have revealed that c-jun and jun B promote growth of fibroblasts, whereas jun D suppresses fibroblast proliferation and even antagonizes Ras-mediated transformation of the fibroblasts. We analyzed effects of gene transfer-mediated jun D overexpression of synovial fibroblast-like cells in patients with RA. METHODS: RA synovial fibroblast-like cells were transiently transfected with jun D expression vector. The transfectants were stimulated with tumor necrosis factor alpha, and their subsequent proliferative responses and proinflammatory cytokine and matrix metalloproteinase (MMP) production at the messenger RNA and protein levels were measured. RESULTS: Transfection with jun D inhibited the proliferation of, and proinflammatory cytokine and MMP production by, RA synovial cells, mainly due to inhibiting their transcription via down-modulation of AP-1 transcription factor. CONCLUSION: Localized jun D transfection into the synovial cells of affected joints may inhibit aberrant synovial cell function in patients with RA by down-regulating gene transcription. This function suggests a possible clinical application of this gene therapy.
10225814 Anti-heat shock protein 70 kDa and 90 kDa antibodies in serum of patients with rheumatoid 1999 May OBJECTIVES: Stress proteins (HSPs) are highly conserved immunodominant antigens found in various species. The purpose of this study was to assess the prevalence and prognostic significance of antibodies to HSC 70 kDa and HSP 90 kDa in three groups of patients with longstanding rheumatoid arthritis (RA) defined based on the severity of articular erosions. METHODS: 73 patients with longstanding (> 6 years) RA whose HLA-DR genotype was known were divided in three groups according to Larsen's score and compared with 47 recent onset (<1 year) RA patients and with control groups composed of patients with other inflammatory diseases (n=137) or of normal controls (n=48). IgGs and IgMs to HSC 70 kDa and HSP 90 kDa were determined using an ELISA with purified bovine HSC 70kDa or HSP 90 kDa. RESULTS: Concentrations of IgGs and IgMs to HSC 70 were significantly increased in 41.1% and 42.5% of longstanding RA patients, respectively. Corresponding figures for IgGs and IgMs to HSP 90 were 39.7% and 56%. IgMs to HSC 70 and HSP 90 were less frequent in recent onset RA (19% and 13% respectively). Among the groups with other inflammatory diseases, only the MCTD group exhibited high frequencies of IgGs to HSC 70 (80%) and HSP 90 (85%). DRB1*0401 positive RA patients (n=23) were not more likely to have increased concentrations of antibodies to HSC 70 kDa or HSP 90 kDa than other RA patients (DR4 positive but DRB1*0401 negative, or DR1 positive, n=31; or negative for both DR4 and DR1, n=14). IgGs to HSP 90 kDa were significantly more frequent (p<0.05) in longstanding RA patients whose Larsen's score was 4 or more (57%) than in those whose Larsen's score was 2 or 3 (39.4%) or less than 2 (16%). No associations were found between Larsen's score and IgGs or IgMs to HSC 70 kDa or IgMs to HSP 90 kDa. A significant correlation was demonstrated between IgGs to HSP 90 kDa and two other serological markers for RA, rheumatoid factor, and anti-Sa antibody; there were no correlations with antikeratin antibody, antiperinuclear factor, or anti-RA 33. CONCLUSION: IgGs to HSP 90 kDa are most common in longstanding RA patients with articular erosions, suggesting that they may be related to the articular prognosis in RA
11333343 Anti-tumor necrosis factor therapies. 2001 May Recently published studies confirm that the long-term use of biologicals targeting tumor necrosis factor-alpha (TNF-alpha) in therapy for rheumatoid arthritis (RA) gives rise to sustained improvement in symptoms and signs of disease provided the anti-TNF agent is efficacious and of low immunogenicity. The current regimens for infliximab 3 or 10 mg/kg infusion in combination with weekly oral methotrexate, or of etanercept 25 mg subcutaneously twice per week, appear to fulfill these criteria. D2E7, a "human" antibody produced by phage display, has also been used for over a year. It has recently emerged that anti-TNF therapy protects joints from structural damage. The 1-year data for infliximab and methotrexate combination therapy suggest that this regimen reduces disability. In early RA, etanercept acts more rapidly than methotrexate to decrease symptoms and retard the progression of erosions. In conclusion, for patients with established and early RA, anti-TNF therapies set a new standard for symptom control and joint protection.
10914848 The importance of gastrointestinal (GI) symptom severity in rheumatoid and osteoarthritis: 2000 Jul OBJECTIVE: To determine the prevalence and stability of gastrointestinal (GI) symptoms in outpatients with rheumatoid arthritis (RA) and osteoarthritis (OA); to determine the specific symptoms that contribute to severity; and to determine the predictive value of GI symptoms and GI severity on the risk of future GI hospitalization. METHODS: A questionnaire survey was mailed to 1221 patients with RA and OA on a continuing 6 month schedule. Patients completed an average of 4.4 questionnaires (n = 5,047). Questionnaires included a visual analog scale GI severity scale, and questions regarding GI hospitalizations and specific GI symptoms. Hospitalizations that were reported as relating to the GI system were audited by checking hospital records. RESULTS: We found 57.5%, 40.2%, and 25.5% of patients had at least one assessment in which they had a GI symptom severity of 0.25-0.99, 1.00-1.99, and 2.00 or greater, respectively. Overall 74.9% had at least one score of 0.25 or greater, and 73.6% had one score of < 0.25, the cutoff for GI symptoms. By contrast, 6.45% had a GI hospitalization, and in only 0.75% of the questionnaire assessments were hospitalizations noted. Pyrosis and peptic ulcer symptoms were common, and were found in 62.5% and 42.4% of patients and 28.2% and 12.9% of observations, respectively. Among patients reporting GI severity scores between 2 and 3, roughly 60% and 45% reported the presence of pyrosis and peptic ulcer symptoms, respectively. The presence of a GI severity score > or = 0.25 was associated with 2.8-3.0-fold increase in the risk of hospitalization over the following 6 months. CONCLUSION: These data suggest that symptoms have an importance of their own that relates to quality of life, regardless of the risk of serious GI events like hospitalization, and that more attention should be placed on symptoms and symptom severity in future research. In spite of the statistical predictive value of GI symptom severity on future hospitalizations, it is important to recognize that rate of GI hospitalization increases from 0.92 per 100 patient-years to only 2.90 per 100 patient-years when the GI symptom scale goes from approximately zero to positive values. Thus, in spite of its statistical predictive ability, GI symptom severity is a poor clinical predictor of the hospitalizations that occur in patients with rheumatic diseases. Instead, GI symptom severity and specific GI symptoms have a separate importance to patients.
11248661 Messenger-RNA expression of matrix metalloproteinases, tissue inhibitors of metalloprotein 2001 Mar In an effort to elucidate the role of mechanical stimuli in rheumatoid arthritis, we determined mRNA levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, and three transcription factors (c-fos, ets-1, and ets-2) under two mechanical shearing conditions as well as simulated unloading. Human synovial cell cultures (MH7A and RA99-01), derived from rheumatoid arthritis patients, were grown for 1 h under mechanical stimuli and the transcript level was assayed by the reverse transcription-polymerase-chain reaction procedure. First, gentle shearing, estimated at approximately 1 dyn/cm(2), induced a consistent decrease in mRNA level of MMP-1, MMP-3, MMP-13, and ets-1 and an increase in the transcript level of TIMP-1, TIMP-2, c-fos, and ets-2. Second, intermediate shearing, estimated at approximately 6 dyn/cm(2), elevated the mRNA level of all MMPs, TIMPs, and the three transcription factors. Third, minimum mRNA level of c-fos, ets-1, and ets-2 was achieved under control conditions at rest, gentle shearing, and simulated unloading, respectively. These in vitro results support a stimulus-dependent transcriptional regulation of MMPs, TIMPs, and transcription factors in cell cultures, suggesting a potential role of shear stress in tissue degradation and prevention in rheumatic joints.
9150068 Prospectively measured red cell folate levels in methotrexate treated patients with rheuma 1997 May OBJECTIVE: To investigate whether red cell folate (RCF) levels relate to side effects, withdrawals, or disease activity during treatment with the folic acid antagonist methotrexate (MTX) for rheumatoid arthritis (RA). METHODS: Side effects were recorded monthly, RCF levels were measured by lactoglobulin binding radioassays, and 8 variables for disease activity were measured in a placebo controlled double blind trial of 28 weeks' duration comparing efficacy of MTX (n = 23) and D-penicillamine (n = 23). RESULTS: From Week 20 RCF levels decreased only in the MTX group (p < 0.02), and 5 MTX treated patients withdrew due to side effects. Withdrawals had lower RCF values at Weeks 0 and 9 compared to the remaining patients (p < 0.05). Folate deficiency evolved in 5 patients; 2 of these developed cytopenia. Aberrations in the scheduled dosage increase were related to lower pretreatment values of RCF (p = 0.007). Side effect scores were inversely correlated to RCF values at Weeks 0, 9, and 28 (p < 0.05). RCF levels measured concomitantly with liver enzyme elevation were lower than the remaining values (p < 0.001). When side effects were reported, 96% of concomitantly measured RCF values were below 800 nmol/l. RCF values at entry did not correlate to improvement in any variable for disease activity, or a graded overall improvement. CONCLUSION: RCF levels decrease during MTX treatment and relate to side effects, withdrawals, liver enzyme elevations and aberrant MTX dosage increase, but not to the therapeutic effect. RCF above 800 nmol/l protects against side effects.
9733447 The development of rheumatoid arthritis after recombinant hepatitis B vaccination. 1998 Sep OBJECTIVE: Hepatitis B vaccination has been associated with reactive arthritis and rarely rheumatoid arthritis (RA). We defined the clinical, serologic, and immunogenetic background of patients developing RA, soon after recombinant hepatitis B vaccination. METHODS: The clinical, serologic, and HLA antigens of a cluster of firefighters who developed arthritis after prophylactic recombinant hepatitis B vaccination (5 subjects), as well as a second group of sporadic cases of arthritis (6 patients) after hepatitis B vaccination are described. RESULTS: Ten of 11 patients fulfilled revised American College of Rheumatology criteria for RA. All cases had persistent arthritis for more than 6 months; at 48 months followup 2 cases no longer had inflammatory arthritis. Nine patients required disease modifying antirheumatic drugs. Five subjects were HLA-DR4 positive. HLA class II genes expressing the RA shared motif were identified in 9/11 patients genotyped for HLA-DRbeta1 and DQbeta1 alleles (0401, 0101, or 0404). All the firefighters shared the HLA-DRbeta1 allele 0301 and the DQbeta1 allele 0201, with which it is in linkage disequilibrium. CONCLUSION: These polymorphic residues in the binding site of the MHC class II molecules of the affected patients appear capable of binding some peptide sequences of the recombinant vaccine peptides they received and may be responsible for hepatitis B vaccine triggering development of RA in these cases. Recombinant hepatitis B vaccine may trigger the development of RA in MHC class II genetically susceptible individuals.
9734677 Comparison of the MOS short form-12 (SF12) health status questionnaire with the SF36 in pa 1998 Aug OBJECTIVE: To compare the performance of the MOS SF12 health survey (SF12) with the SF36 in a sample of 233 patients with rheumatoid arthritis (RA) stratified by functional class. METHODS: The SF12 and SF36 physical and mental component summary scales (PCS and MCS) were compared for test retest reliability [intra-class correlation coefficient (RC) and repeatability], construct validity and responsiveness [standardized response mean (SRM)] to self-reported change in health. RESULTS: Overall, despite its brevity, the SF12 is comparable to the SF36 with only some loss of performance. The SF12-PCS is slightly less reliable (RC = 0.75) and responsive to improvements in health (SRM = 0.52) than the SF36-PCS (RC = 0.81; SRM = 0.61). The SF12-PCS correlates strongly with the SF36-PCS (R = 0.94), SF36 physical function subscale (R = 0.77) and modified Stanford Health Assessment Questionnaire (MHAQ) (R = 0.71), but only weakly with the SF36 mental health subscale (R = 0.22). SF12-PCS discriminated well between Steinbrocker functional classes; patients in functional classes 1-4, respectively, have SF12-PCS scores 1sigma, 2sigma, 2.4sigma and 2.7sigma below the population norm (ANOVA, F = 35.8, P < 0.000). The SF12-MCS is relatively unresponsive to reported improvement in RA (SRM = 0.31), but is reliable (RC = 0.71) and correlates well with the SF36-MCS (R = 0.71). SF12-MCS correlates more closely than the SF36-MCS with the SF36 mental health subscale (R = 0.86) and Hospital Anxiety and Depression (HAD) scale (R = 0.76). In ANOVA models, only the HAD (R2 = 57%) score contributes significantly to variance in SF12-MCS (F = 254.8; P < 0.000), but both the HAD (R2 = 24%) and MHAQ (R2 = 10%) scores contribute to variance in the SF36-MCS (F = 50.9; P < 0.000). Thus, the SF12-MCS has better construct validity for mental health than SF36-MCS in RA subjects. Missing responses to items were high amongst patients in functional class 4 (34%). CONCLUSION: The SF12 is a reliable, valid and responsive measure of health status in the majority of RA patients, and meets standards required for comparing groups of patients. Its application in the most severely disabled subjects is uncertain.
11028841 In vitro migration of mononuclear cells towards synovial fluid and plasma from rheumatoid 2000 OBJECTIVE: To evaluate in vitro migration of mononuclear cells towards synovial fluid (SF) and plasma in relation to RANTES synovial fluid levels and clinical disease activity. METHODS: 31 RA patients with synovitis in one knee were included. Modified Boyden chamber technique was used to determine a migratory index defined as: 'In vitro migrating cells towards SF' divided by 'In vitro migrating cells towards plasma'. RANTES was quantified by ELISA. Disease activity was assessed by the swollen joint count, the Ritchie articular index (RAI), global assessment, pain on VAS, HAQ, ESR and CRP. RESULTS: A positive significant correlation was found between the migratory index and the RANTES levels in SF (r=0.48, p=0.006), the RAI (r=0.56, p=0.0001) and pain on VAS (r=0.43, p=0.04). The in vitro migration could be inhibited in 3 of 4 SF samples by neutralising antibodies towards RANTES (12-18%). CONCLUSION: The migratory index correlate to SF levels of RANTES and parameters for joint pain.
9032817 Correlation between anti-Proteus antibodies and isolation rates of P. mirabilis in rheumat 1997 In a survey of 89 RA patients, carried out under code, Proteus mirabilis was isolated from the urine of 63% (47/75) of female (P < 0.001) and 50% (7/14) of male patients (P < 0.001), compared to a frequency of isolation in healthy women of 32% (38/119) and 11% (13/115) in healthy men. There was no significant difference in isolation rates between 37 non-RA patients and healthy controls. Sera from 20 patients with RA and 20 healthy controls were tested against P. mirabilis and Escherichia coli by an enzyme-linked immunosorbent assay. Antibodies against P. mirabilis but not to E. coli were significantly higher in the RA patients than in healthy controls (P < 0.001). Furthermore, a positive correlation was found between high anti-Proteus antibody levels in serum samples and the number of Proteus colony-forming units obtained from urine specimens of the 20 RA patients (r = +0.714, P < 0.001). These results support the suggestion of an aetiopathogenic role for P. mirabilis in RA.
9710991 [Benign rheumatoid nodules. Report of 4 cases]. 1998 Jul Benign rheumatoid nodules are subcutaneous nodules morphologically and histologically identical to the ones appearing in patients with rheumatoid arthritis. They usually happen in healthy people without neither clinical nor serologic manifestations of any rheumatic illness. These nodules are more usual in children and they are considered exceptional beyond the age of eighteen. In the literature, only two hundred cases in children and twenty five cases in adults have been properly documented, with histological confirmation. We report four new cases of benign rheumatoid nodules histologically proved, two children and two adults, and we confirm the optimistic prognosis of these patients.
10088945 Circulating P- and L-selectin and T-lymphocyte activation and patients with autoimmune rhe 1999 Circulating levels of P- and L-selectins and the degree of T-lymphocyte activation were assessed by enzyme-linked immunosorbent assays in 75 selected patients with rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) at various clinical stages, and in 40 healthy blood donors matched for age and gender. Mean levels of P-selectin were significantly higher than normal in RA (lower in patients with clinical remission) and SSc (higher in patients with early-onset diffuse disease), but not in SLE. In contrast, mean L-selectin levels were significantly higher than normal in SLE (no correlation to the degree of disease activity), but not in RA or SSc. Mean levels of soluble interleukin-2 receptors (sIL-2R), reflecting mainly T-lymphocyte activation, in patients with active RA, SSc and SLE were almost double the normal level; however, correlations between individual levels of circulating P- or L-selectins and sIL-2R within groups revealed a strong positive correlation only between L-selectin and sIL-2R (r = 0.66, p<0.001), and only in patients with SLE. Given the different expression of P- and L-selectins, these findings indicate a distinct pattern of immune cell activation in chronic diseases that share an overactivation of T-lymphocytes. The possible clinical value of quantitation of circulating P-selectin in patients with RA and SSc on the one hand, and L-selectin in patients with SLE on the other, should be investigated by prospective studies.
11247638 Toxic shock syndrome toxin-1 accelerated collagen-induced arthritis in mice. 2001 Mar The aim of this study was to explore the roles of toxic shock syndrome toxin-1 (TSST-1) in collagen-induced arthritis (CIA). DBA/1 mice were immunized with type II collagen (CII) and treated with TSST-1. Intraperitoneal and intravenous injections of TSST-1 aggravated CIA, enhancing its incidence and severity. CIA was accompanied by an increase in anti-CII IgG Ab levels. Intraperitoneal administration with TSST-1 enhanced IFN-gamma, TNF-alpha, and IL-4 production in DBA/1 mice. We discovered the mRNA expressions of IFN-gamma, IL-2, TNF-alpha, IL-1beta, and iNOS in spleen cells stimulated with TSST-1 in vitro. However, IL-12 and IL-4 mRNA expression were seen constitutively without stimulation. Only a little increase of IL-12 and IL-4 mRNA expression was seen at 2-3 h after treatment with TSST-1. Our experiments demonstrated that CIA was aggravated by the treatment with TSST-1, which may have induced various proinflammatory cytokines and the production of both Th1 and Th2 cytokines.
11441118 Lymphoid neogenesis in rheumatoid synovitis. 2001 Jul 15 In rheumatoid arthritis (RA), tissue-infiltrating lymphocytes can be arranged in sophisticated organizations that resemble microstructures usually formed in secondary lymphoid organs. Molecular pathways and host risk factors involved in this process of lymphoid neogenesis remain to be defined. In a series of 64 synovial tissue biopsies, lymphoid follicles with germinal centers (GCs) were found in 23.4% of the patients. Follicular dendritic cells (FDCs) were exclusively present in tissues with GCs, suggesting that the recruitment or in situ maturation of FDCs is a critical factor for GC formation in the synovial membrane. Primary follicles were absent, emphasizing the role of Ag recognition in the generation of inflammation-associated lymphoid organogenesis. Multivariate logistic regression analysis of tissue cytokines and chemokines identified two parameters, in situ transcription of lymphotoxin (LT)-beta and of B lymphocyte chemoattractant (BLC; BLC/CXCL13), that were predictors for FDC recruitment and synovial GC formation. LT-beta and BLC/CXCL13 were found to be independent variables that could, in part, compensate for each other to facilitate GC formation. Prediction models incorporating in situ transcription of LT-beta and BLC/CXCL13 had high negative yet moderate positive predictive values, suggesting that LT-beta and BLC/CXCL13 are necessary but not sufficient. LT-beta protein was detected on a subset of mantle zone and GC B cells, but also on T cells in follicular structures. BLC/CXCL13 was produced by FDCs in follicular centers, but was predominantly found in endothelial cells and synovial fibroblasts, suggesting heterotypic signaling between cells of the synovial membrane and infiltrating lymphocytes in regulating extranodal lymphoid neogenesis.
9846895 Advanced glycation endproducts (AGE) on IgG, a target for circulating antibodies in North 1998 Nov Several tribes of North American Indians are known to have poor glucose control and are at a high risk of developing type 2 diabetes. Similarly some tribes also exhibit RA at a high frequency. We have recently determined that a subset of Caucasian patients with RA mount an immune response to IgG modified with advanced glycation endproducts (AGE). The AGE modifications on IgG in vivo include N(epsilon)-(carboxymethyl) lysine, imidazolone and pentosidine. The presence of IgG-AGE and the antibody response to the IgG-AGE in the Ojibwe tribe of First Nations native Indians where both NIDDM and RA are prevalent was investigated. AGE modified IgG and albumin were determined using a modified nitroblue tetrazolium assay. Rheumatoid factors (RFs) and IgM and IgA anti-IgG-AGE were detected by ELISA. Of the 108 individuals tested, 21 had RA only, 3 had both RA and type 2 diabetes, 30 had type 2 diabetes only and 51 had no diagnosed disease. AGE modified IgG was significantly elevated in the RA group compared to the diabetic group. IgM and IgA RFs were detected in 83% and 50% of the RA patients, compared to 31-37% and 7-10% of the diabetics or normal individuals. IgM anti-IgG-AGE was detected in 54% of the RA patients, in contrast to 7-14% in the diabetics or normal individuals. IgA anti-IgG-AGE was detected in 42% of the RA patients and only 7 to 8% of the NIDDM or normal individuals. The IgM or IgA anti-IgG-AGE antibodies likely contribute to the accumulation of IgG-AGE, possibly through blocked clearance through AGE receptors. A trend towards more severe disease was seen in those Ojibwe RA patients with circulating anti-AGE antibodies. Non-enzymatic glycation may be an important pathogenic link in the RA seen in North American Indians.
10577961 Changes in the incidence and prevalence of rheumatoid arthritis in Kamitonda, Wakayama, Ja 1999 Dec OBJECTIVE: To evaluate secular trends in the incidence and prevalence of rheumatoid arthritis (RA) in Japan. METHODS: The incidence and prevalence of RA were determined in a longitudinal population based study in the Kamitonda district, Wakayama, Japan, from 1965 to 1996. RESULTS: In the study area consisting of about 3000 inhabitants, 16 incident cases, satisfying definite RA by the Rome criteria were detected during the study period. The age and sex adjusted incidence in both men and women combined and the age adjusted incidence in women significantly decreased (p<0.025 and p<0. 01, respectively). The age and sex adjusted prevalence in all inhabitants tended to decrease (p<0.1), and the age adjusted prevalence in women significantly declined (p<0.025). In men, however, neither incidence nor prevalence showed significant change. CONCLUSIONS: The decline of incidence and prevalence of female RA may be reducible to some environmental changes preferentially occurring more obviously in Japanese women than in men. Because the use of oral contraceptives has been extremely low in Japan, the decline should be explained by other factors.