Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1674762 | Recognition of human 60 kD heat shock protein by mononuclear cells from patients with juve | 1991 Jun 8 | A postulated mechanism for autoimmune disorders is that the immunoreactivity develops against bacterial antigens which show a high degree of sequence homology with mammalian proteins. The mycobacterial 65 kD heat shock protein (hsp) has been implicated in several forms of arthritis. Substantial amounts of the human 60 kD homologue (hsp60) were produced by insertion of the gene into Escherichia coli. To investigate the hypothesis that T-cell reactivity is directed against the endogenous hsp, T-cell proliferation of synovial-fluid and peripheral-blood mononuclear cells in response to hsp60 was studied in samples from six patients with juvenile chronic arthritis (JCA) and nine adult patients with rheumatoid arthritis (RA). There was no T-lymphocyte proliferative response to purified fractions of hsp60 in mononuclear cells from RA patients or healthy children and young adults. However, both synovial-fluid and peripheral-blood mononuclear cells from JCA patients showed substantial proliferative responses. There was a significant correlation between the stimulation indices for human hsp60 and for mycobacterial hsp65 (r = 0.948, p less than 0.02). A similar correlation for hsp60 and mycobacterial hsp70 did not achieve significance. Immunohistochemistry showed that hsp65 and hsp70 homologues were expressed in the synovial membrane in these patients but not in controls. These findings suggest a sequence of events in which hsps become expressed during synovial inflammation and function as autoantigens. In JCA this may be manifested by specific T-cell reactivity which apparently is lost in the more bone-eroding and non-remitting adult disease. | |
| 2229914 | Arthrodesis of the first metatarsophalangeal joint: a review of the literature and long-te | 1990 Jul | A retrospective analysis of arthrodesis of the first metatarsophalangeal joint was done to determine the procedure's long-term subjective and objective results. The authors reviewed the long-term results of arthrodesis in 25 patients with 32 operated feet. The average age was 54.8 years (range 22 to 72 years), and the average length of follow-up was 31.9 months (range 12 to 84 months). The patients were questioned regarding pain, activity, cosmesis, and willingness to have the operation performed again. The subjective results were good or excellent in 26 feet (81% success rate). The primary postoperative complaints were pain in the interphalangeal joint (four feet), and a callosity or pain under the first metatarsal head (four feet). Radiographic examination revealed that the procedure provided a good reduction of the hallux valgus angle (preoperative average 33.7 degrees; postoperative average 17.4 degrees) and intermetatarsal angle (preoperative average 16.2 degrees; postoperative average 12.0 degrees). The authors believe that this procedure is a reliable, effective treatment whenever stability is required at the first metatarsophalangeal joint. | |
| 3259355 | [Synovial level of interleukin 1 and C3a in chronic polyarthritis, psoriatic arthritis and | 1988 Jan | Concentrations of interleukin-1 (IL-1), C3a des Arg and immune complexes (IC) were investigated in knee effusions of patients with rheumatoid arthritis (RA; n = 36), psoriatic arthritis (Ps.A., n = 19) and osteoarthritis (n = 7). Maximal concentrations of IC and C3a des Arg were found in RA patients, high IL-1-activities could be demonstrated in patients with Ps.A. and seropositive RA. We found significant correlations between IL-1 and C3a des Arg, IL-1 and IC and C3a des Arg, and IC in Ps.A. patients, but not in RA or osteoarthritis patients. The role of IL-1 in the chronic inflammatory response and joint destruction in inflammatory joint diseases is discussed. | |
| 3741502 | Treatment of Felty's syndrome with low-dose oral methotrexate. | 1986 Jul | Recent studies of methotrexate in the treatment of patients with rheumatoid arthritis have precluded patients with neutropenia. We present a patient with rheumatoid arthritis complicated by severe neutropenia and recurrent infections, who was treated with low-dose methotrexate, orally, for 30 months. The patient experienced symptomatic improvement and a significant increase in granulocyte count, and the dosage of steroids was reduced. Low-dose oral methotrexate may be a therapeutic option in select patients with Felty's syndrome. | |
| 2086016 | [The clinical significance of antibodies to SM, RNP and SSR polypeptides detected by immun | 1990 Aug | Using immunoblotting technique (IBT) antibodies to Sm, RNP and SSB polypeptides we detected in 173 patients with different rheumatic diseases. It was found that antibodies to Sm polypeptides with molecular weights of 28K(B) and 13.5K(D) could be detected almost only in SLE (34.0% and 30.0% respectively). The positive rates of anti-28K and anti-13.5K polypeptides in SLE detected by IBT were significantly higher than those of anti-Sm by counterimmunoelectrophoresis (12.0%) (P less than 0.05). The antibodies to SSB polypeptides with molecular weights of 48K and 43.41K could be detected mainly in Sjogren's syndrome (70.0% and 65.0% respectively) and the antibodies to RNP polypeptides with molecular weights of 68K, 32K(A) and 29K (B') mainly in MCTD (82.6% 100% and 34.8% respectively) (P less than 0.001). It was reported by Pettersson that anti-68K polypeptide had high specificity for the diagnosis of MCTD. But our data showed that the anti-68K polypeptide could also be detected in SLE(26.0%) and PSS(15.0%) and was not so specific for MCTD. | |
| 3180585 | The effect of postoperative collateral ligament laxity in total knee arthroplasty. | 1988 Nov | Forty-seven patients who had been treated by 63 total knee arthroplasties were assessed at 12-84 months after the operation. The data were analyzed to determine if collateral ligament laxity had a detrimental effect on the clinical outcome. The Hospital for Special Surgery (HSS) score was used to make the clinical assessment and a modified HSS score, which excluded points awarded for laxity, was also used. Unidirectional (varus or valgus) and total (varus and valgus) laxity were used as a basis of analysis. None of the examined parameters produced results suggesting that lax knees were worse than stable knees. Indeed, knees with increasing laxity through the categories of mild and moderate showed better statistically significant results in HSS score and pain than those with lesser degrees of laxity. Seventy-five percent of the knees with unidirectional laxity were classified as excellent; only 38.5% of the stable knees were graded as excellent (p less than 0.01). Only 9% of the lax knees had complaints of pain; 38% of the stable knees were painful (p less than 0.05). No significant difference in functional score and walking ability was noted between the lax and the stable knees. Seventy-eight percent of the lax knees had a range of motion over 100 degrees; 62.5% of the stable knees achieved this range. | |
| 2390123 | Low levels of interleukin-4 and high levels of transforming growth factor beta in rheumato | 1990 Aug | Since interleukin-4 (IL-4) displays agonistic effects on both T and B cells, we studied whether this lymphokine is involved in rheumatoid synovitis, a disease characterized by intense T cell infiltration and B cell stimulation. Rheumatoid arthritis synovial fluids (RA SF) contained no (less than 15 pg/ml) or very low amounts (less than 25 pg/ml) of IL-4, as measured by a sensitive and specific enzyme-linked immunosorbent assay. No IL-4 was produced by unstimulated rheumatoid synovial membrane. RA SF were found to inhibit phorbol myristate acetate (PMA)-dependent proliferation of normal peripheral blood lymphocytes (PBL). An inhibitory fraction with an apparent molecular weight of 150 kd was isolated by gel filtration. The inhibitory fraction strongly blocked the proliferation of PBL induced by PMA, PMA + IL-2, or PMA + IL-4. However, this fraction was less effective in blocking the proliferation of PBL induced by PMA + IL-2 + IL-4. High levels of transforming growth factor beta (TGF beta) were found in these RA SF, and an anti-TGF beta antibody was able to partially reduce the inhibitory activity. RA SF were found to inhibit phytohemagglutinin-induced IL-4 production by PBL. These data indicate that IL-4, similar to other T cell lymphokines, cannot be detected in RA SF and that RA SF contains an inhibitory activity, related in part to TGF beta, which blocks mitogen-induced proliferation of PBL, at least in part through an inhibition of T cell-derived lymphokine release. | |
| 2170067 | Degradation of human myelin in vitro by leucocytes from patients with multiple sclerosis. | 1990 Oct | In order to study the possible autoimmune basis of multiple sclerosis (MS) a quantitative method has been used to investigate breakdown of human myelin in vitro. We found that serum from MS patients and controls was generally devoid of any myelin degradative activity. However, isolated peripheral blood mononuclear cells from 43% of MS patients showed significant myelin degradative activity as did those from 61.5% of patients with rheumatoid arthritis (RA). Myelin degradation by cells was found in only 13% of patients with other neurological diseases and in no healthy controls. It is proposed that this non-specific peripheral cellular immune degradative activity originates from cells activated within the central nervous system of MS patients or the joints of individuals with RA. As a result, activity in the blood only indirectly reflects the ongoing inflammatory response at the primary site, accounting for the lack of correlation between changes in the blood and the clinical status of the MS patient. We further propose that the lack of in vitro myelin degradative activity in cells recovered from the cerebrospinal fluid is due to autoaggressive cells being sequestered to the brain. | |
| 1697427 | Comparative study of assays detecting complement activation. Complement-split product C3d | 1990 Jun | The aim of the study was to investigate the correlation between two types of assay measuring specific products of complement C3 activation and their clinical application. Complement C3d split product was estimated using double-decker rocket immunoelectrophoresis (DD-RIE) and measurements of C3d neodeterminants exposed after C3 activation was carried out with an enzyme-linked immunosorbent assay (ELISA). A total of 595 blood samples were measured in parallel in the DD-RIE and the ELISA test systems. The samples originated from blood donors (44), uraemic patients undergoing dialysis (135), serial samples from rheumatoid arthritis (RA) patients during steroid treatment (88) and 328 randomly collected patient samples. The mean values for DD-RIE and ELISA (+/- 1 SD) for the 595 samples were 48 (+/- 20) mU/l and 48 (+/- 28) mU/l respectively. The interassay coefficient of variation (CV) in the ELISA was 18%. The Spearman rho-correlation coefficient between the two assays was 0.63 for all 595 samples. The mean values using ELISA and DD-RIE were practically identical for the 328 successively incoming samples, the samples from the 135 dialysis patients and the 44 donors. In RA patients a higher mean value was found for the 88 samples using DD-RIE than ELISA. In the majority of patient samples there was a good correlation between the two assays. However, the ELISA appears to be more sensitive in detecting acute complement activation and to give lower levels in RA patients with chronic complement activation. | |
| 2241286 | Significance of low molecular weight C1q in systemic lupus erythematosus. | 1990 Sep | The significance of high serum concentrations of low molecular weight C1q (LMW-C1q) in patients with systemic lupus erythematosus (SLE) was studied. Concentrations of LMW-C1q were increased in SLE, but not in rheumatoid arthritis or acute poststreptococcal glomerulonephritis. Concentrations of LMW-C1q in SLE serum samples correlated with titres of anti-dsDNA and were inversely related to concentrations of normal C1q and C3. Serial studies in six patients, who had rising anti-dsDNA titres and who developed a major exacerbation requiring admission to hospital, showed that LMW-C1q increased in parallel with anti-dsDNA, reaching peak values of more than 2000% of normal just before or at the time of clinical relapse and decreasing during convalescence. Most marked increases in LMW-C1q were noted in the three patients in whom C1q concentrations remained normal, whereas increases were less in the three patients who had strongly depressed concentrations of normal C1q. A study of C1q biosynthesis by macrophages cultured from patients with SLE and high serum concentrations of LMW-C1q did not show impaired secretion of normal C1q in favour of LMW-C1q, but indicated that serum concentrations of LMW-C1q may reflect the synthetic rate of C1q in vivo. The results show that increased serum concentrations of LMW-C1q may be helpful in diagnosing SLE and suggest that serial determination of LMW-C1q in serum may have predictive value in monitoring patients with SLE. | |
| 1660794 | Functional characterization of SV40-transformed adherent synovial cells from rheumatoid ar | 1991 Dec | A total of 14 transformed cell clones were obtained by micro-injecting origin-defective SV40 DNA into three types of cloned adherent synovial cells (ASC) (dendritic cells (DCs), macrophage-like cells (MCs), and fibroblast-like cells (FCs)) from two rheumatoid arthritis patients (five DC clones (SV40-DCs), five MC clones (SV40-MCs) and four FC clones (SV40-FCs)). All the transformed cell nuclei expressed SV40-specific T antigen. The cells which formed a colony had a few times shorter doubling time than the original cells. IL-1 alpha, IL-1 beta and prostaglandin E2 were detected in the culture supernatant from the unstimulated transformed cells like untransformed cells. The SV40-DCs showed the most potent accessory cell function in oxidative mitogenesis assay among the three types of SV40-ASCs. Granulocyte macrophage colony stimulatory factor (GM-CSF) was detected only in the culture supernatant from the SV40-MCs without stimulation. Extensive phenotypic analysis revealed relatively cell-specific markers. SV40-DCs were HLA-DP+ and glial fibrillary acidic protein positive. SV40-MCs stained positive for 5'-nucleotidase and nonspecific esterase. These transformed ASCs retained much of the original cellular physiology of rheumatoid arthritis (RA) ASCs and may be a useful tool for characterizing the role of ASCs in the pathogenesis of RA. | |
| 1683150 | Nonsteroidal peptic damage in rheumatoid patients receiving second-line drugs. | 1991 Nov | Using endoscopy, we assessed the prevalence of peptic ulceration in 281 rheumatoid patients receiving nonsteroidal antiinflammatory drugs alone, or in combination with second-line agents. Ulcers were found in 33 of 96 patients who took nonsteroidals only (33/96, 34%), compared with 8/33 (24%) on hydroxychloroquine, 10/30 (33%) on penicillamine, 13/46 (28%) on sulphasalazine, but only 11/76 (14%) on intramuscular gold plus nonsteroidals (chi 2 = 7.95, 0.001 less than p less than 0.01, p less than 0.05 using Bonferroni correction). Second-line drugs do not seem to increase the prevalence of ulcers related to nonsteroidal antiinflammatory drugs; on the contrary, fewer ulcers were found in patients receiving gold therapy, and this might have therapeutic implications. | |
| 3620277 | Double-blind multicentre UK hospital studies of isoxicam vs naproxen. | 1986 | 1 Two multicentre, parallel group, randomised, double-blind, double-dummy comparison studies were conducted between isoxicam in the usual dose of 200 mg once daily and naproxen 500 mg twice daily. 2 The drugs were administered for 4 weeks to 230 patients suffering from osteoarthritis of the hip and/or knee in the first trial and to 249 patients suffering from rheumatoid arthritis in the second. 3 The studies compared treatments for both safety and overall effectiveness in the relief of pain. 4 In the osteoarthritis trial, overall pain was reduced by both drugs after 2 weeks of therapy but only isoxicam produced further improvement after 4 weeks. 5 Isoxicam produced reductions comparable to those produced by naproxen in pain on standing from the sitting position, pain on walking, and pain on movement of the affected joint, after 2 and 4 weeks. 6 After 4 weeks, isoxicam given once daily in the morning was significantly more effective than naproxen given in the morning and the evening in relieving not only total pain as assessed by a visual analogue scale but, as importantly, night pain. 7 Compared to naproxen therapy, isoxicam therapy was associated with significantly more patients whose disease state was improved at 2 weeks, as assessed by physicians. 8 In the rheumatoid arthritis trial, isoxicam was equally as effective as naproxen in reducing joint tenderness, joint swelling, and pain; at 4 weeks there was a trend in favour of isoxicam in reduction of joint swelling and pain. 9 Isoxicam reduced morning stiffness significantly more than naproxen after 4 weeks; this trend was apparent at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3394096 | [Respiratory disorders in Sjögren's syndrome: its comparison with scleroderma and normal | 1988 | The respiratory system was evaluated in 40 patients with primary Sjogren's syndrome (pSS) and its involvement was compared with that of 26 patients with secondary Sjogren's syndrome (sSS), 40 with rheumatoid arthritis (RA), 30 with scleroderma and 100 matched healthy controls using questionnaire, physical examination and functional criteria (spirometry, flow/volume curve, total lung capacity, diffusion). The commonest clinical manifestation in pSS patients was dry cough either alone (xerotrachea) or in combination with dyspnea (indicative of diffuse interstitial lung disease). Functional analysis revealed that 38% of pSS patients had impaired diffusion and 25% impaired flow/volume curve (indicative of small airways disease). Interstitial lung involvement was more common in extraglandular pSS (52% versus 21% in glandular). However no pSS patient was incapacitated from pulmonary disease and when pulmonary function was compared with that of scleroderma and healthy controls it was shown that the dysfunction in primary Sjogren's syndrome was much less serious than in scleroderma and not much different from that of healthy controls. The respiratory involvement in sSS differed since it was more suggestive of obstructive lung disease (19%) in a way very similar to that of rheumatoid arthritis. The results indicate that pulmonary involvement in pSS although frequent is not clinically important. They also suggest that sSS does not add pulmonary manifestations to RA. The differences in pulmonary involvement between pSS and sSS further support the thesis that they are different disease entities. | |
| 1723358 | Antibodies to dietary antigens in rheumatoid arthritis--possible molecular mimicry mechani | 1991 Dec 16 | Antibodies in serum from some patients with rheumatoid arthritis, recognize bovine albumin present in the milk, as determined by immunoprecipitation analysis from 125I-milk extracts. This antigen was also immunoprecipitated from bovine sera. These and ELISA studies showed that BSA is preferentially recognized over other proteins present in the milk. Panel studies demonstrated that although the average reactivity for BSA was high, only one third of the sera tested displayed a reactivity above the mean. The possibility of a molecular mimicry mechanism in RA between this food antigen and other human antigens was investigated. A sequence alignment analysis showed that the residues 141-157 of bovine albumin significantly differed from the corresponding fragment of human albumin, but were highly homologous with human collagen type I, C1q and vitamin D binding protein. In support of the immunogenicity of this fragment, we found that representative RA sera displayed a specific reactivity for a synthetic peptide containing the BSA residues responsible for the homology. Furthermore, most of the epitopes recognized on BSA by the RA sera seem to be conformationally dependent as heat denaturation or reduction followed by alkylation lead to a diminished recognition. | |
| 2450134 | HLA-DR4 restricted lymphocyte proliferation to a Mycobacterium tuberculosis extract in rhe | 1988 Mar 15 | The ability of an antigenic extract of Mycobacterium tuberculosis to induce proliferation of PMBC from rheumatoid arthritis (RA) patients and normal controls was examined. The subjects were further classified as bearing or not bearing the HLA-DR4 phenotype, since this specificity is regarded as a genetic determinant commonly associated with RA. The mycobacterial extract induced significantly higher proliferative responses in lymphocytes from all HLA-DR4 positive as compared to HLA-DR4 negative subjects regardless of whether they had RA or not. This response was maximal at day 6 of incubation and could be abrogated by anti-DR/DQ mAb added to the culture. SDS-PAGE of this extract revealed three major protein bands located at Mr 14, 47, and 65 kDa. After fractionation, Western blotting, and resuspension of protein-laden nitrocellulose particles, only the 14- and 47-kDa proteins retained the original proliferative capacity of the mycobacterial extract. The band separating with a Mr of 47 kDa was found to be the most strongly associated with the HLA-DR4 restricted lymphocyte proliferation, and represents a newly identified M. tuberculosis Ag of relevance in T cell responses. These data provide insight into the pathogenic potential of certain bacterial Ag which could trigger or perpetuate inflammatory disorders when presented in the appropriate genetical background. | |
| 2950233 | Peripheral blood T lymphocyte subpopulations determined by monoclonal antibodies in active | 1986 Oct | The introduction of an automated flow cytofluorograph has facilitated the detection of T lymphocyte subsets because it enables a larger number of cells to be analyzed. Many authors have reported a decrease of cytotoxic/suppressor T lymphocytes in rheumatoid arthritis (RA), in contrast to the results of other workers. We believe that the discrepancy between the various studies is due to the fact that different methods and different criteria for patient selection were used. Our study comprised a larger number of patients which makes the results suitable for statistical inference. Disease activity is clearly defined and all drugs that could alter the results were excluded. The use of a flow cytometer enhances the reliability of T lymphocyte subset determination by monoclonal antibodies (OKT series). Our study confirms the reports, which suggested that the number of suppressor/cytotoxic T lymphocytes (OKT8+ cells/mm3) is decreased in patients with active RA, resulting in a high T helper/inducer lymphocyte/T suppressor/cytotoxic lymphocyte ratio (OKT4+:OKT8+). This immune balance represents an interesting feature of the disease, since several active antirheumatic drugs share a common immunomodulatory action, which normalizes the OKT4+:OKT8+ ratio. Finally, we found a good correlation between the OKT4+ cells and OKT8+ cells in the normal control population. This observation enabled us to isolate a subgroup of active patients with RA not responding to slow acting antirheumatic drugs and characterized by a low OKT4+:OKT8+ ratio. | |
| 1974162 | Association of osteoarthritis with homozygosity for a 5.8 kb Taq I fragment of the alpha 1 | 1990 Aug | The genes coding for the protease inhibitors alpha 1-antitrypsin (A1AT) and alpha 1-antichymotrypsin (A1ACT) were analysed by Southern blot in patients with rheumatoid arthritis, psoriatic arthritis, psoriasis without arthritis, polymyalgia rheumatica and generalized osteoarthritis. The probe/restriction enzyme combinations used were the 4.6 kb 5' fragment of the A1AT gene with the Sst I enzyme, the 6.5 kb 3' fragment of the same gene with Taq I and the 3.4 kb fragment of A1ACT with Taq I. The frequency of homozygous genotype for the 5.8 kb A1ACT band was increased in osteoarthritis (62.8% versus 36.8%, P = 0.01, relative risk = 2.9, aetiological fraction = 0.41). No other disease association was found with any marker. This suggests that the A1ACT gene may influence susceptibility to generalized osteoarthritis. | |
| 2828614 | Elastase and collagenase activities in synovial fluid of patients with arthritis. | 1987 Oct | The activity of elastase and collagenase was measured in the synovial fluid (SF) of 24 patients with inflammatory and 6 patients with traumatic joint effusions. The enzyme activity was compared with local and systemic variables of the disease. Elastase and collagenase activity could be detected in 79 and 83%, respectively, of the arthritic SF, whereas no enzyme activity was found in the traumatic joint effusions. The SF enzyme activity showed no correlation with clinical, laboratory or radiographic variables of arthritis in the joint from which the fluid was obtained. Our results show that proteolytic enzyme activity in SF may help to distinguish inflammatory from noninflammatory joint effusions but does not reflect the severity of the arthritic process. | |
| 2115831 | Neutrophil functional and arachidonic acid metabolic correlates and clinical disease activ | 1990 | Neutrophils from 20 medication-free rheumatoid arthritis patients were chemotactically hyporesponsive to 2 x 10(-8) M formyl-methionyl-leucyl-phenylalanine (f-MLP) as compared to 20 normal controls. They were relatively high producers of 5-hydroxyeicosatetraenoic acid (5-HETE) and low producers of leukotriene C4 (LTC4). Neutrophils from 10 patients treated with pirazolac (4-(4-chlorophenyl)-1-(4-fluorophenyl)-5-pyrazole acetic acid) showed increased chemotactic responsiveness concomitantly with normalization of 5-HETE and LTC4 production and a decrease in the clinical parameters of disease activity. Clinically attainable (30-60 micrograms/ml) in-vitro doses of pirazolac further depressed the chemotactic responsiveness of normal neutrophils treated with 10(-5)M f-MLP. Effects on endothelial gating of migrating neutrophil populations may explain this apparent contradiction between in-vivo and in-vitro actions of pirazolac on neutrophil chemotaxis. |