Browse

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

ID PMID Title PublicationDate abstract
8620620 The mechanism of autoantibody formation to cartilage in rheumatoid arthritis: possible cro 1996 May In order to study the mechanism of autoantibody formation to type II collagen in rheumatoid arthritis (RA), IgG and IgA antibodies in sera from 259 RA patients and 285 non-RA controls were evaluated for their specificity as to collagen type (I and II) and species (chick, bovine, and porcine) using an improved enzyme-linked immunosorbent assay. IgG and IgA anti-type II collagen antibodies were commonly found in both RA (IgG, 41%; and IgA, 45%) and non-RA (IgG, 36%; and IgA, 31%) sera. Both IgG and IgA collagen antibodies were highly reactive with one or more heterologous type II or type I collagen; however, approximately 35% of IgG and 50% of IgA antibody-positive sera from both RA patients and non-RA controls cross-reacted with human type II collagen (HII) to some degree. However, no antibodies specific to HII were observed in either RA or control sera. In individual patient sera, IgG and IgA antibodies had identical collagen-type and species specificities. Importantly, IgG anti-HII antibodies purified from RA sera by affinity chromatography reacted equally with human, chick and bovine type II collagens, suggesting reactivity with conserved epitopes shared by all three species. In contrast, purified IgG anti-HII antibodies from non-RA control sera commonly lacked reactivity with one or the other of the heterologous type II collagens, suggesting reactivity limited to epitopes shared by HII and only one of the heterologous type II collagens. These data suggest that dietary collagens could elicit circulating IgG and IgA anti-collagen antibodies that cross-react with autologous type II collagen. Also the epitope specificity of IgG autoantibodies may be relevant to the pathogenesis of RA.
7637324 Differential expression of collagen types I, II, III, and X in human osteophytes. 1995 Aug BACKGROUND: Osteophytes are neoplastic cartilaginous and osseous protrusions growing at the margins of osteoarthritic joints. Their formation involves complex patterns of cellular proliferation, differentiation, as well as matrix synthesis and turnover that are poorly understood. EXPERIMENTAL DESIGN: Here we report on an experimental approach using in situ hybridization and immunohistology to elucidate pathways of chrondrocyte differentiation in human osteophytes. Ab and cDNA probes for collagen types were used as specific parameters for chondrocyte phenotypes. RESULTS: In early precartilaginous mesenchymal tissue, cytoplasmic mRNA for alpha 1(I) and alpha 1(III) collagen genes (Col1A1 and Col3A1) were found by in situ hybridization, correlating with the distribution of type I and III collagen as revealed by Ab staining. Strong expression of type II collagen both at mRNA and protein levels was the hallmark of chondrogenic differentiation in the cartilaginous zone of osteophytes. Type II collagen expression increased in all cartilaginous and fibrocartilaginous areas with growth and maturation of osteophytes. The signal intensity obtained after in situ hybridization with a COL2A1 probe was high and corresponded to that obtained in fetal cartilage, whereas normal adult articular cartilage usually did not show measurable type II collagen expression. In fibrocartilaginous areas, the most abundant, but heterogeneous tissue type seen in osteophytes, type II and III collagen mRNA expression overlapped considerably. Type III collagen was scattered, both pericellularly and interterritorially, over the whole osteophyte, excluding bone and chondrocytic cells of the deep zone. The strongest type I collagen expression was seen in bone and in the superficial fibrous layer. In areas of endochondral ossification, large chondrocytes were found expressing type X collagen, a specific marker for hypertrophic chondrocytes. CONCLUSIONS: These results show that discrete stages of cartilage differentiation can be precisely followed in osteophytes using collagen type-specific cDNA probes and Ab as markers. In addition, a fibrocartilaginous chondrocyte phenotype was identified that expresses type II and III, but not type I collagen.
8814068 Local disruption of the insulin-like growth factor system in the arthritic joint. 1996 Sep OBJECTIVE: To identify differences in levels of insulin-like growth factor (IGF) and IGF binding proteins (IG-FBPs) between 30 patients with arthritis (14 with rheumatoid arthritis [RA], 16 with osteoarthritis [OA]) and 11 normal control subjects. IGF and IGFBP levels were correlated to the disease activity marker C-reactive protein (CRP) to determine whether they were disease related. We also examined the degree of proteolytic modification of the IGFBPs. METHODS: Radioimmunoassays were used for measuring IGF and IGFBP-3 levels; CRP was measured by enzyme-linked immunosorbent assay. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting, chemiluminescence, and autoradiography were used for visualizing binding proteins. RESULTS: There was a significant increase in synovial fluid levels of both IGF-1 and IGFBP-3 in both RA and OA. This resulted in an elevated IGFBP-3 to IGF molar ratio of 1.49 in the OA group and 1.47 in the RA group, compared with 0.86 in the normal control group (P = 0.0002 for both). A significantly lower degree of IGFBP-3 proteolysis was also seen in the synovial fluids from the patients compared with the controls. There were significant correlations between the CRP level and levels of IGF-1, IGF-2, and IGFBP-3 in the RA patients (r = 0.62-0.898, P = 0.04-0.0007). CONCLUSION: There was significant local disruption of the IGF system in patients with arthritis. This may result in a lower amount of IGF that is able to bind to IGF receptors in the arthritic joint. Levels of IGF-1 IGF-2, and IGFBP-3 all correlated with the CRP level in patients with RA, which indicates the possibility that the IGF system is involved in the disease process.
1387596 T lymphocyte adhesion to fibronectin (FN): a possible mechanism for T cell accumulation in 1992 Sep The accumulation of T cells within the joint is responsible for the perpetuation of synovitis. This process is partly regulated by selective binding to endothelium. However, adhesion to extra-cellular matrix proteins, like FN, may also be important. FN binding is mediated by certain members of the VLA (beta 1 integrin) family of proteins. To investigate the role of Tc-FN interactions in synovitis the binding of synovial fluid (SF) and peripheral blood (PB) T cells to FN-coated wells, and the expression of cell surface VLA molecules on these cells by double label immunofluorescence, were studied. SF T cells bound better to FN than PB T cells. VLA alpha 4 and VLA beta 1 but not VLA alpha 5 were up-regulated on SF compared with PB T cells. Anti-VLA alpha 4, VLA beta 1 and VLA alpha 5 MoAbs inhibited the binding of SF T cells to FN. The increased binding of SF T cells to FN could have been related to activation and/or to their predominantly memory phenotype. Purified resting memory or naive T cells bound poorly to FN. In contrast, compared with SF T cells, concanavalin A-activated T cells showed a very similar level of binding to FN, comparable expression of VLA molecules and the same pattern of inhibition of binding to FN by MoAbs. Thus, VLA molecules may play an important role in the retention of T cells in the joint and since T cells can be activated via VLA-FN interactions, this mechanism may perpetuate chronic inflammation.
9374445 Demonstration of interleukin-1beta and interleukin-6 in cells of synovial fluids by flow c 1996 Feb 22 Cytokine levels are increased in the synovial fluid of affected joints from patients with inflammatory joint diseases. The aim of our study was therefore to determine if and to what extent immmunologically defined subpopulations of mononuclear cells (MNC) in the synovial fluid are responsible for the increased levels of interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in affected joints. Lipopolysaccharide (LPS) stimulated peripheral MNC were used as positive controls. While soluble IL-1beta (median 167 pg/ml) and IL-6 (median 508 pg/ml) levels were significantly elevated in the synovial fluids tested, IL-1beta and IL-6 were demonstrated by flow cytometry in only a small subpopulation (<=11%) of mononuclear synovial fluid cells in 7/13 patients. Our results suggest that elevated IL-1beta and IL-6 levels in the synovial fluid of inflammatory joints are derived mainly from cells in the synovial membrane and only to a minor extent from cells in the synovial fluid itself.
9010051 Synovial fluid interleukin-8 and neutrophil function in rheumatoid arthritis and seronegat 1996 Dec The relationships between synovial fluid (SF) interleukin-8 (IL-8) and neutrophil turnover as measured by cytidine deaminase (CD), and SF metabolites were studied in 28 patients, 16 with rheumatoid arthritis (RA; median age and disease duration 62 and 14 yr, respectively) and 12 with seronegative polyarthritis (SNP; median age and disease duration 32 and 5 yr, respectively). Knee SF samples were aspirated using indwelling cannulae following a period of rest for 1 h. SF IL-8 levels (measured by an ELISA) were significantly elevated in RA compared to SNP (median 2.35 vs 0.22 ng/ml, P < 0.001), as were median levels of CD (55.8 vs 8.11 U/ml, P < 0.01), lactic acid (29.6 vs 16.6 mg/dl, P < 0.001), glucose (57.9 vs 84.5 mg/dl, P < 0.05) and the lactate to glucose ratio (0.85 vs 0.19, P < 0.001). Measures of disease activity, C-reactive protein, plasma viscosity and articular index were also elevated in RA compared to SNP (P < 0.05). SF IL-8 levels correlated strongly with CD, lactate, glucose and the lactate to glucose ratio when both disease groups were considered together (P < 0.001). These parameters also showed some association with the measures of disease activity (P < 0.05). All these associations were less marked when the individual disease groups were analysed separately. These results suggest that factors responsible for neutrophil accumulation and priming (probably IL-8) are present in SF, and these coincide with products of their activation (CD). The degree of neutrophil turnover is linked to the anaerobic metabolism of the synovial cavity.
1376892 [Interactions between peptides and major histocompatibility complex molecules]. 1992 Mar T-cell receptors recognize foreign proteins as peptide fragments associated with major histocompatibility complex (MHC) molecules. Properties of antigenic peptides, methods for detecting peptide-MHC molecule combinations, and the characteristics of the interaction are reviewed. Possible explanations for graft rejection and autoimmune disease are suggested in the light of these data.
8112199 A placebo-controlled study of the efficacy and tolerability of a nonsteroidal anti-inflamm 1993 A double-blind, randomized, placebo-controlled study has been carried out in order to assess the effects of the new topical cutaneous formulation, diclofenac hydroxyethylpyrrolidine (DHEP) plaster. Sixty patients (10 M + 50 F, mean age 56.6 yrs) suffering from local inflammatory processes in peri-articular/tendinous and/or extra-articular sites were involved in this study and randomly given either DHEP plaster or placebo plaster. Plasters were applied and left on the site of inflammation b.i.d. (at 8 a.m. and 8 p.m.) for 14 days. Patients under stabilized systemic treatment with NSAIDs, glucocorticoids and/or basic therapy for over 2 months, maintained this treatment unchanged during the course of the study. Patients were examined on days 3, 5, 7 and 14. The effects of the treatments were assessed using subjective, semi-quantitative (provoked pain, peri-articular swelling, doctor-patient judgement, telethermographic index) and quantitative variables (spontaneous pain measured using a visual analogical scale). In the peri-articular pathologies, spontaneous and provoked pain decreased faster and in a clinically relevant manner in the group treated with DHEP plaster compared to the control group (p < 0.01). Local inflammation, objectively evaluated using the telethermographic index, showed consistent reduction during the study which was statistically significant from day 3 onwards and significantly different compared to the control group. Global assessment of efficacy, expressed by the investigator and the patients, was significantly better (good to excellent after only 7 days in 70% of the cases) in the DHEP group compared to the placebo group. In the extra-articular pathologies, results similar to those reported earlier were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)
1394437 Estrogen accelerates immune complex glomerulonephritis but ameliorates T cell-mediated vas 1992 Oct 1 Estrogen is known to influence immune responses in healthy subjects in a dichotomous fashion. Thus, in number of previous studies we and others have demonstrated that B cell activities are augmented after exposure to estrogen whereas T cell reactivity is suppressed. Furthermore, it has been shown that this hormone has significant impact on the course of certain human and experimental autoimmune diseases. In this study we report that treatment with physiological doses of estradiol exerts dichotomous effects on different manifestations of the lupus disease in MRL/l mice. On one hand immune complex-mediated glomerulonephritis was significantly accelerated. This outcome was due to polyclonal B cell activation with increased production of antibodies to double-stranded DNA and formation of circulating immune complexes. In contrast, T cell-mediated lesions such as focal sialadenitis, renal vasculitis, and periarticular inflammation were all significantly ameliorated in MRL/l mice exposed to estrogen. Thus, we were able to demonstrate that, within one subject and even within one organ, administration of estrogen leads to differential outcome of SLE morbidity. We propose that the differential effect of estrogen on the manifestations of the autoimmune disease of MRL/l mice is due to its dichotomous effects on B and T cell-mediated immune responses.
8911074 [Clinical significance of anti-centromere antibody and anti-CENP-B antibody in sera of pat 1996 Sep Anti-centromere antibody (ACA) have been recognized in sera of patients with primary biliary cirrhosis (PBC) and CREST syndrome. The major reactive antigen of ACA have been identified as CENP-B (80kDa). Using an indirect immunofluorescence (IIF) method and ELISA method, we detected ACA and anti-CENP-B antibody in patients with PBC and various liver diseases and collagen diseases. We tested sera of 44 patients with PBC, 8 patients with autoimmune hepatitis (AIH), 51 patients with chronic hepatitis B (CH-B), 312 patients with chronic hepatitis C(CH-C), 12 patients with progressive systemic sclerosis (PSS), 10 patients with systemic lupus erythematosus (SLE), 10 patients with rheumatoid arthritis (RA), and 30 with healthy subjects (HS). ACA was detected by IIF technique, using HEp-2 cell and fluoro-CENTRO slides (MBL) as substrates. Anti-CENP-B antibody was detected by ELISA method using recombinant CENP-B (MBL) as the antigen. ACA was detected in sera of 12 (27%) patients with PBC, two (25%) patients with AIH, five (2%) patients with CH-C, nine (75%) patients with PSS, and one (10%) patients with RA. ACA was not detected in sera of patients with CH-B and SLE and in HS. The results of IIF test for ACA, using HEp -2 cells and fluoro-CENTRO slides, were completely agreed. Anti-CENP-B antibody was detected in 28(97%) out of 29 patients sera positive for ACA. The titers of ACA and anti-CENP-B antibody did not show a correlation (r = 0.24). Out of 12 sera, in which, the titers of anti-CENP-B antibody was over 400. Among them, eight were patients with PBC and four were PSS. Later, out of four patients with PSS, three (75%) were found to be positive for anti-mitochondrial antibody. Out of five patients, in which the titer of anti-CENP-B antibody showed over 800, all were patients with PBC. The titers of ACA have no relationship with PBC. However, the titers of anti-CENP-B antibody have closed relationship with PBC. The reason why the titers of ACA and anti-CENP-B antibody were not correlated is unknown. We consider anti-CENP-B antibody is a new marker of a subset of PBC, because almost all the patients were PBC when this antibody showed over 400.
7743657 Detection of anti-topoisomerase I antibodies using a full length human topoisomerase I rec 1995 May Topoisomerase I (topo I) is a major systemic sclerosis (SSc)-associated autoantigen. A cDNA construct encoding full length human topo I in a recombinant baculovirus transfer vector was used to infect insect cells in culture from which recombinant protein was purified. An ELISA using recombinant protein was evaluated in 340 sera including sera from 134 patients with SSc, of whom 33 had anti-topo I antibodies detected by immunodiffusion. A high yield of pure topo I of expected molecular mass and catalytic activity was obtained. The recombinant topo I ELISA was 92% sensitive and 98% specific in detecting anti-topo I antibodies which were present almost exclusively in patients with SSc. Therefore, the potential advantages of expressing human autoantigens in eukaryotic systems for diagnostic purposes were confirmed.
7977023 Oxygen free radicals and antioxidants: a review. 1994 Sep In 1989, nearly 43% of deaths in the United States were due to some form of cardiovascular disease, and 23% were caused by cancer. Thus, two of every three people in this country die from either cardiovascular disease or cancer. Based on both experimental and epidemiological evidence, investigators believe that free radicals play a critical role in the development of both diseases. Low levels of antioxidants, which increases free radical activity, are clearly associated with an increased risk of these diseases. This link has led to the conclusion that use of antioxidant vitamin supplements to scavenge free radicals could potentially decrease the risks of cancer and cardiovascular disease. Results from numerous studies to date have been very promising, although a true protective or preventive causal relationship has not yet been established. Numerous primary and secondary intervention trials currently underway should more definitively assess the role of antioxidants in disease prevention. In the interim, many people feel the evidence is now strong enough to begin supplementation on their own. The pharmacist is in a position to advise patients on the safe and moderate use of antioxidants. The antioxidants discussed in this article are relatively non-toxic, with the exception of vitamin A. The possible benefits of vitamin A are better achieved with the use of beta-carotene. Megadose antioxidant supplementation does not appear to provide any additional benefit beyond what a more moderate supplement can provide and should therefore be discouraged. Taking a trace mineral with antioxidant potential is generally a waste of money, provided the patient is not initially deficient in the element.(ABSTRACT TRUNCATED AT 250 WORDS)
8242020 [Rheumatologic manifestations in heart transplant recipients. A cross-sectional study of 3 1993 Jan Rheumatological complications are sometimes disabling in heart transplant recipients and may negate the good results obtained with transplantation. The objective of this study was to evaluate the incidence of these complications. 365 consecutive heart transplant recipients (292 males and 73 females) were systematically interviewed and examined according to a standardized protocol. The mean age of the patients was 45.9 +/- 12.0 years (range: 11-68). The mean duration from transplantation to time of the study was 35.8 +/- 25.6 months (range: 1-115). The rheumatological disorders most frequently encountered were: gout, osteoporosis, osteonecrosis and myalgias. Early-onset polyarticular gout was diagnosed in 63/365 patients (17.3%). This diagnosis was significantly associated with patient's age, time since transplant, male sex, serum uric acid, serum creatinine, diuretics intake and inversely associated with the serum cyclosporin levels. Hyperuricemia was observed in 75.9% of transplant recipients with a mean of 507.5 +/- 132.5 mumol/l (range: 97-965). An osteoporotic fracture was present in 18/365 patients (4.9%) and was significantly associated with the patient's age, but not with the dose of corticosteroids. Osteonecrosis was detected in 10/365 patients (2.7%), always affected the hip, and was significantly associated with the patient's age, but not with the high doses of steroids. Myalgias were reported by 14/365 patients (3.8%). Laboratory, electromyographic and histological analysis were negative. Rheumatological complications are frequent in heart transplant recipients and justify preventive and therapeutic management.
7980675 Increased usage of V beta 2 and V beta 6 in rheumatoid synovial fluid T cells. 1994 Nov OBJECTIVE: To determine if the T cell antigen receptor V beta usage of unstimulated rheumatoid arthritis (RA) synovial fluid (SF) T cells is biased compared with those in peripheral blood (PB). METHODS: Freshly isolated, matched synovial fluid and peripheral blood T cells were analyzed for V beta gene expression using quantitative polymerase chain reaction (PCR) methods. Ten synovial fluid samples from the knees of 7 patients with RA were studied. The PCR assay used 26 V beta primers with a constant region C beta primer, and 2 C alpha primers that co-amplified a product that served as an internal standard. Cycle number and complementary DNA content were controlled to ensure the linear accumulation of PCR products. Labeled products were separated on 10% polyacrylamide gels and counted with a Betascope blot analyzer. RESULTS: There were consistent differences between the V beta gene usage of SF and PB T cells directly isolated from patients with RA, regardless of HLA-DR haplotype. In all synovial specimens, V beta 2 was increased relative to the peripheral blood, while V beta 13.1 and V beta 13.2 were decreased. V beta 6 and V beta 21 were increased in 9 of the 10 synovial samples. Analyses of bilateral SF specimens from 2 subjects and serial specimens from the same knee of 1 subject revealed virtually identical patterns in each patient. The SF V beta bias was not solely due to differences in the proportion of CD4+ and CD8+ cells, because the CD4:CD8 ratios in SF and PB were similar. However, V beta gene usage of separated CD4+ and CD8+ synovial T cells showed that V beta 2 and V beta 6 were more highly expressed on CD4 cells. CONCLUSION: Freshly isolated synovial T cells from inflamed (not end-stage) knees of patients with RA have a remarkably consistent biased V beta gene usage compared with PB T cells. V beta 2 and V beta 6 are uniformly increased, and this increase is primarily in CD4+ T cells. The same V beta bias in the SF T cells of several RA patients suggests that shared antigens may be stimulating the T cell response.
1571092 Monoclonal antibodies defining shared human macrophage-endothelial antigens. 1992 We have selected several monoclonal antibodies (mAbs) producing using human rheumatoid arthritis (RA) synovial macrophages (m phi s) as immunogen. Of these, mAbs 8H2, 10G7 and 10G9 showed cross reactivity with endothelium, suggesting common antigens between these cell types. We have determined the spectrum of reactivity of these mAbs on hematopoietic cell lines, peripheral blood cells, and inflammatory and non-inflammatory tissues by immunohistochemistry. MAb 8H2 does not react with the myeloid cell lines HL60 (myelocytic), U937 (histiocytic lymphoma), and K562 (erythroleukemia), or with peripheral blood cells. In normal and inflamed tissue sections, mAb 8H2 reacts with m phi s and endothelial cells. In contrast, mAb 10G7 does not react with peripheral blood cells, but reacts with HL60, U937, and K562 cell lines, as well as with m phi s and endothelial cells in inflamed and noninflamed tissues. MAb 10G9 does not react with myeloid cell lines, but reacts with monocytes and platelets in peripheral blood. In both normal and inflamed tissues, mAb 10G9 reacts with m phi s and endothelial cells. The antigens identified by these three mAbs were characterized biochemically, by enzymatic digestion of RA synovial tissue m phi s followed by a cellular ELISA, as well as by reactivity of the mAbs with NIH-3T3 cells genetically engineered to express known myeloid antigens. These mAbs reacted with protein or glycoprotein antigens distinct from the known myeloid antigens CD13, CD14, CD33, CD34, CD36, and c-fms. These mAbs should prove to be a valuable tool for studying m phi s and endothelial cells and their shared antigenic determinants.
7514466 Circulating levels of insulin-like growth factor-I and -II, and IGF-binding protein-3 in i 1994 Jan In order to assess if the anabolic action of PTH is related to changes in circulating levels of insulin-like growth factor-I and -II (IGF-I and -II), and IGF binding protein 3 (IGFBP-3), 24 h of PTH infusion was performed in healthy women and in patients with rheumatoid arthritis (RA), a state where both bone metabolism and PTH secretion is influenced by the inflammatory activity. The patients with RA had lower basal levels of both IGF-I and -II than the healthy controls (P < 0.05). In neither group did the IGFs change after 24 h of PTH administration, while IGFBP-3 was significantly increased in the healthy controls (4600 +/- 1200 to 5750 +/- 2200 micrograms/l, P < 0.05). IGFBP-3 was not affected by PTH infusion in patients with RA when the disease had high activity, but when inflammation had subsided they responded with a similar increase in IGFBP-3 as the control group and basal IGF-I and -II levels were normalised. Since IGFBP-3 can enhance the anabolic action of IGF-I, increased IGFBP-3 levels after PTH infusion may reflect a mechanism by which PTH is anabolic for bone. Inflammation may inhibit bone formation via decreased serum levels of IGFs and blocked IGFBP-3 response to PTH.
7759034 [Therapy of rheumatic disease with a hydroxyethylsalicylate gel. Results of 2 clinical stu 1995 Mar 20 Two clinical studies were carried out to investigate the efficacy and safety as well as the local and systemic availability of a hydroxyethylsalicyclate gel. A double blind, multicenter trial, involving 113 patients with nonarticular rheumatic back pain, revealed statistically significant relief of pain as compared with placebo. Local and systemic tolerance was excellent. An open study of bioavailability after local application in 16 patients showed a mean salicylate concentration of 0.93 +/- 0.5 microgram/ml in the synovial fluid and 0.40 +/- 0.23 microgram/ml in the synovial membrane, compared with 0.14 +/- 0.04 microgram/ml in the serum. Genetisinic acid was not detected, while OH-hippuric acid was detected only in the serum and synovial fluid.
8996468 Tenidap in patients with rheumatoid arthritis. A 4-week, placebo-controlled study. 1996 The present double-blind, placebo-controlled study was conducted to compare the safety and efficacy of tenidap in patients with rheumatoid arthritis (RA). Patients with flare of active RA following NSAID withdrawal were randomized to receive either placebo (n = 67) or tenidap (n = 131; 40-200 mg/day). The mean changes from baseline in efficacy and biochemical variables were compared between treatment groups at endpoint (4 weeks). The improvements in four of the five primary efficacy variables were significantly greater in the tenidap group compared with the placebo group (p < 0.01). Tenidap was also associated with an 18% reduction in erythrocyte sedimentation rate (ESR) and a marked, 51%, reduction in serum C-reactive protein (CRP) level, both of which were significantly greater than the changes in the placebo group (p < 0.05). The percentage of patients who discontinued because of side effects was the same in both groups (3%). In conclusion, tenidap 40-200 mg/day was effective and well tolerated in the treatment of patients with RA for 4 weeks.
8608631 Increased numbers of CD5+ B cells and T cell receptor (TCR) gamma delta+ T cells are assoc 1996 Mar Patients presenting with RA before the age of 45 years (younger onset) are known to have more aggressive disease compared with patients presenting after the age of 65 years (older onset). Coordinated expansion of circulating CD5+ B cell and TCR gamma delta+ T cell levels has been reported in patients with RA. This study assesses the peripheral blood levels of these two cell types in RA patients with younger and older onset of disease. CD5+ B cell levels were significantly elevated in the younger onset RA group (26.6+/-4.5%) compared with the older onset RA group (14.2+/-1.2%; P<0.01). TCR gamma delta+ T cell levels were also significantly raised in the young patients (4.0+/-0.9%) compared with elderly patients (1.6+/-0.2%; P<0.01). T cell levels (CD3+) were similar in both groups (young 66.4+/-3.3%; old 74.3+/-3.4% (mean+/-s.e.m.); NS). Total B cell levels (CD19+) were also similar in these groups (7.7+/-0.7% versus 8.9+/-1.8%; NS). A significant positive correlation was observed between the CD5+ B and TCR gamma delta+ T cell types in the patients (r=0.72, P<0.05). Compared with age-matched normal controls, the younger onset patients had similar CD5+ B cell and TCR gamma delta+ T cell levels to the elderly controls (CD5+ B cells 30.2+/-3.0%; TCR gamma delta+ T cells 3.0+/-0.8%). Conversely, older onset RA patients had CD5+ B cell levels similar to the young controls (12.3+/-1.9%). Spontaneous in vitro synthesis of immunoglobulins (IgM, IgA and IgG) and rheumatoid factors (IgM and IgA isotypes) were not significantly different in both patient groups. The coordinate expansion of circulating CD5+ B cells and gamma delta+ T cells seen in patients with RA presenting before 45 years of age and not after 65 years of age may suggest a potential role for these cells in more aggressive disease states.
8040330 Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells 1994 Aug Experiments were designed to test the hypothesis that chronic exposure to tumor necrosis factor alpha (TNF) alters the function of activated T lymphocytes. Pretreatment of tetanus toxoid-specific T cell clones with TNF for up to 16 d impaired rechallenge proliferative responses to antigen in a dose- and time-dependent fashion. IL-2 and PHA responses were preserved. Prolonged treatment with TNF impaired production of IL-2, IL-10, IFN gamma, TNF, and lymphotoxin (LT) following stimulation with immobilized OKT3, and resulted in suboptimal expression of the IL-2R alpha chain (Tac) but not CD3, CD4, or HLA-DR antigens, when compared to untreated control cells. By contrast, pretreatment of T cells for prolonged periods in vitro with neutralizing anti-TNF monoclonal antibodies (mAb) enhanced proliferative responses, increased lymphokine production, and upregulated Tac expression following stimulation with OKT3. To determine whether TNF exerts immunosuppressive effects on T cells in vivo, we studied cell-mediated immunity in patients with active rheumatoid arthritis (RA), before and after treatment with a chimeric anti-TNF mAb. Treatment with anti-TNF restored the diminished proliferative responses of PBMC to mitogens and recall antigens towards normal in all patients tested. These data demonstrate that persistent expression of TNF in vitro and in vivo impairs cell-mediated immune responses.