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

PMID	Title	PublicationDate	abstract
3456197	Genetic interrelationship between insulin-dependent diabetes mellitus, the autoimmune thyr	1986 Feb	To investigate the possible coinheritance of autoimmune diseases that are associated with the same HLA antigen, we studied 70 families in which at least two siblings had either type I diabetes mellitus (IDDM), autoimmune thyroid disease (ATD), rheumatoid arthritis (RA), or a combination of these diseases. HLA-A, B, and C typing was performed on all affected sibs in one generation or more. First, we estimated by sib-pair analysis the disease allele frequency (pD) and the mode of inheritance for each disease. According to the method of ascertainment entered into the analysis, the pD for ATD ranged from .120 to .180, for an additive (dominant) mode of inheritance. For RA, the pD ranged from .254 to .341, also for additive inheritance, although recessive inheritance could not be excluded. For IDDM, the pD ranged from .336 to .337 for recessive inheritance; additive inheritance was rejected. Second, we examined the distribution of shared parental haplotypes in pairs of siblings that were discordant for their autoimmune diseases. The results suggested that the same haplotype may predispose to both IDDM and ATD, or IDDM and RA, but not to both RA and ATD. Analysis of pedigrees supported this hypothesis. In 16 families typed for HLA-DR also, the haplotype predisposing to both IDDM and ATD was assigned from pedigree information to DR3 (44%), DR4 (39%), or DR5, DR6, or DR7 (5.5% each). In some families, these haplotypes segregated over several generations with ATD only (either clinical or subclinical), suggesting that in such families, ATD was a marker for a susceptibility to IDDM. In several families, an IDDM haplotype segregated with RA but not with ATD. This suggests that ATD- and RA-associated susceptibilities to IDDM may be biologically different and thus independently increase the risk of IDDM.
1954640	Treatment of arthritis with topical capsaicin: a double-blind trial.	1991 May	The neuropeptide substance P has been implicated in the pathogenesis of inflammation and pain in arthritis. In this double-blind randomized study, 70 patients with osteoarthritis (OA) and 31 with rheumatoid arthritis (RA) received capsaicin (a substance P depletor) or placebo for four weeks. The patients were instructed to apply 0.025% capsaicin cream or its vehicle (placebo) to painful knees four times daily. Pain relief was assessed using visual analog scales for pain and relief, a categorical pain scale, and physicians' global evaluations. Most of the patients continued to receive concomitant arthritis medications. Significantly more relief of pain was reported by the capsaicin-treated patients than the placebo patients throughout the study; after four weeks of capsaicin treatment, RA and OA patients demonstrated mean reductions in pain of 57% and 33%, respectively. These reductions in pain were statistically significant compared with those reported with placebo (P = 0.003 and P = 0.033, respectively). According to the global evaluations, 80% of the capsaicin-treated patients experienced a reduction in pain after two weeks of treatment. Transient burning was felt at the sites of drug application by 23 of the 52 capsaicin-treated patients; two patients withdrew from treatment because of this side effect. It is concluded that capsaicin cream is a safe and effective treatment for arthritis.
2254887	Adherent synovial cells from nonrheumatoid arthritis do not release interleukin 1 beta and	1990 Oct	Adherent synovial cells from both 13 patients without rheumatoid arthritis (RA) (gout, osteoarthritis and meniscal lesion) and 8 patients with RA consisted of dendritic cells, macrophage-like cells and fibroblast-like cells after cloning in a similar fashion as reported in our previous paper. All the adherent synovial cells from patients without RA did not release interleukin 1 (IL-1) beta and prostaglandin E2 (PGE2) spontaneously, while those cells released comparable amounts of IL-1 beta, but not PGE2 to RA cells after type II collagen stimulation. Only the synovial cells from RA, irrespective of morphology and cloning, released IL-1 beta and PGE2 without stimulation. Nonrheumatoid synovial cells may differ functionally from RA cells.
2634367	Quantitative determination of rheumatoid factors in serum and synovial liquid of patients	1989 Apr	The rheumatoid factors constitute one of the major autoantibodies in rheumatoid arthritis (RA). In this study, for the quantitative determination of the RF IgM class, in serum and synovial liquid of patients with RA and JRA, we used the hemagglutination principle and both liquid and lyophilized reagents. The results we obtained demonstrated the superiority regarding the stability, the reproducibility and the possibility of micromethod standardization with lyophilized reagent.
2514058	Susceptibility to rheumatoid arthritis--the conformational equivalence hypothesis.	1989 Sep	The occurrence of the inappropriate immune response of rheumatoid arthritis is likely controlled by several alleles of class II DR beta chain genes of the major histocompatibility complex (MHC). These include certain of those that encode the serologically distinct DR1 and DR4 specificities. In a manner analogous to a segregation analysis, advantage was taken of ethnic differences in susceptibility associated with different alleles and parallel differences in the organization of the class II haplotypes that specify either similar or divergent serologic specificities. This permitted mapping of this disease susceptibility into a single equivalent polymorphic alpha helical conformation shared by each DR beta allelic product. This suggests that rheumatoid arthritis originates from a unitary immune recognition event initiated by particular class II MHC molecules.
1890495	Psychiatric illness in patients with chronic fatigue and those with rheumatoid arthritis.	1991 Jul	OBJECTIVES: To identify psychiatric differences between patients with chronic fatigue and those with rheumatoid arthritis and to investigate whether patients meeting Centers for Disease Control (CDC) criteria for chronic fatigue syndrome (CFS) can be differentiated from patients with chronic fatigue on measures of disability and psychosocial distress. DESIGN: Cross-sectional study comparing 98 patients with chronic fatigue with 31 patients with rheumatoid arthritis on structured psychiatric interviews and patient questionnaires. Nineteen patients meeting CDC criteria for CFS were compared with 79 patients with chronic fatigue not meeting CDC criteria on questionnaires measuring disability and psychosocial distress. SETTING: Consecutive patients with chronic fatigue were selected from a chronic fatigue clinic at the University of Washington, and 31 consecutive patients with rheumatoid arthritis were sampled from a private rheumatology practice. MAIN RESULTS: Patients with chronic fatigue had a significantly higher prevalence of lifetime major depression and somatization disorder than did patients with rheumatoid arthritis. Patients with chronic fatigue also had a significantly higher prevalence of current and lifetime psychiatric diagnoses. Only 19 of 98 patients with chronic fatigue met CDC criteria for CFS. Patients meeting CDC criteria for CFS could not be differentiated from the larger group of patients with chronic fatigue on any study variable. CONCLUSIONS: Patients with chronic fatigue have a significantly higher burden of psychiatric illness than do patients with rheumatoid arthritis. The psychiatric illness preceded the development of chronic fatigue in over half the patients. Centers for Disease Control criteria for CFS did not select a subset of chronic fatigue patients who could be differentiated on disability or psychosocial parameters from patients with chronic fatigue who did not meet CDC criteria.
3776692	C-reactive protein in population samples.	1986	The significance of C-reactive protein (CRP) was studied in three different sets of specimens. Raised levels (greater than 10 mg/l) were detected in 2.0% of 380 healthy blood donors from whom two blood specimens, taken at an interval of half a year, were tested. Except for two cases, only one of the two specimens was positive. Raised levels were found three times as frequently (in 6.6%) in a random middle-aged population sample consisting of 531 subjects. More than 40% of the raised levels could be connected to acute respiratory infections, and about 20% to smoking. Five of the 35 subjects (14%) in the population sample with elevated CRP had rheumatoid arthritis. The third set of sera comprised pre-illness specimens from 22 subjects who developed rheumatoid arthritis a few months to five years later. Although it had previously been proved that the majority of these sera contained rheumatoid factors, the CRP concentration was increased in one specimen only.
2467350	Analysis of rheumatoid factor autoantibodies in patients with essential mixed cryoglobulin	1988	Approximately 60% of human monoclonal rheumatoid factors from unrelated patients with cryoglobulinaemia share a common idiotype (Wa). Analysis of Ig V regions revealed that these rheumatoid factors utilize highly homologous light chains from the VKIIIb sub-subgroup. More recent studies showed a similar restriction in the use of VHI and JH4 and a restriction in the size of the D segment. In the present experiments the structural features of RFs from patients with cryoglobulinaemia were studied using a panel of murine monoclonal antibodies. The pattern of expression of these idiotypes were investigated among diverse patients with rheumatoid arthritis and normal individuals. Though in general higher levels of crossreactive idiotypes from the Wa group are detected in rheumatoid arthritis patients compared to normals, their levels in polyclonal rheumatoid factors is low. Therefore the major proportion of polyclonal rheumatoid factors in rheumatoid arthritis represent the products of somatic variants of monoclonal rheumatoid factor V genes or a larger gene pool.
3545900	[Dynamics of the joint pains at night in rheumatoid arthritis and arthroses treated with R	1986 Nov	The effect of a novel nonsteroidal antiinflammatory drug Rengasil on pain at rest in rheumatoid arthritis and arthroses was studied in comparison with piroxicam and placebo. Intensity of nocturnal pains was estimated according to the "visual analogous scale". The relationship between the time of occurrence of a complete analgesic effect and severity of the pain syndrome before the beginning of monotherapy was established.
2774054	Immunohistochemical localization of HTLV-I p19- and p24-related antigens in synovial joint	1989 Jul	In formalin-fixed, paraffin-embedded synovial tissues from patients with early proliferative rheumatoid arthritis (RA), immunoreactivity could be demonstrated utilizing monoclonal IgG antibodies reactive with the p19 and p24 protein of human T cell leukemia virus (HTLV-I). Additionally, surgical specimens of fresh unfixed synovial tissues from patients with RA also demonstrated immunoreactivity. At the light microscopic level, both HTLV-I antigens were detected in approximately 45% of the rheumatoid synovial tissues by the immunocolloidal gold method with silver enhancement (IGSS) and the avidin-biotin-complex technique (ABC), whereas six of eight of the frozen RA specimens stained positive by immunofluorescence. Patients whose synovial tissues were immunoreactive by immunofluorescence were seronegative to HTLV-I antigens as determined by ELISA and immunoblotting. Conversely, cases with osteoarthritis, juvenile rheumatoid arthritis, psoriatic arthritis, Dupuytren's contracture, and gangrene were shown to be nonreactive by immunohistochemistry. The results indicate that expression of antigens is related to or crossreactive with HTLV-I in synovial tissues from patients with rheumatoid arthritis.
1771401	Rheumajecta and vasolastine in the treatment of rheumatoid arthritis--the results of a pla	1991	The so called "enzymatic preparations" Rheumajecta and Vasolastine (R & V) belong to the complementary treatments. The preparations have been used for many years in the treatment of patients with rheumatic conditions such as rheumatoid arthritis (RA) in the Netherlands and other countries of Europe, although a proper study showing efficacy was never performed. Therefore a double-blind, placebo-controlled, modified cross-over trial during two periods of 3 months was performed in 34 patients with RA. They were allocated at random to R & V or to placebo injections, all intramuscular. After 3 months of therapy each patient could opt for cross-over in the event of lack of subjective improvement. Clinical assessments including Ritchie's articular index, grip strength, the DUTCH-AIMS questionnaire, ESR and CRP were performed. R & V did not prove to be more effective than placebo. No serious side-effects were seen.
3293571	Network regulation in rheumatoid arthritis. Studies of DR+ T cells, anti-DR, antiidiotypic	1988 Jul	We prospectively studied rheumatoid arthritis patients with various degrees of clinical disease activity, for the presence of DR+ T cells by flow cytometry, for anti-DR using immunoblot analysis, and for antiidiotypic (anti-id) antibodies by enzyme-linked immunosorbent assay using F(ab')2 monoclonal antibody anti-DR L243 as idiotype. DR+ T cells correlated positively with anti-DR, and anti-id correlated negatively with both DR+ T cells and anti-DR. Active clinical disease correlated positively with both DR+ T cells and anti-DR, and correlated negatively with anti-id. This DR antigen/anti-DR/anti-id network may control disease activity in rheumatoid arthritis patients.
1698773	Discoordinate expression of stromelysin, collagenase, and tissue inhibitor of metalloprote	1990 Oct 5	Primary and passaged human synovial fibroblasts isolated from rheumatoid pannus were treated with recombinant interleukin-1 (IL-1) alpha or beta, tumor necrosis factor-alpha (TNF), or phorbol myristate acetate (PMA) to determine the effects of these stimuli on the relative expression of stromelysin, collagenase, and tissue inhibitor of metalloproteinases (TIMP). The steady-state mRNA levels for these genes and glyceraldehyde-3-phosphate dehydrogenase were determined on Northern blots. Immunoblot analyses of the conditioned media using monoclonal antibodies generated against recombinant human stromelysin, collagenase, or TIMP showed that protein levels reflected the corresponding steady-state mRNA levels. The results revealed that 1) stromelysin and collagenase were not always coordinately expressed; 2) IL-1 was more potent than TNF or PMA in the induction of stromelysin expression; 3) neither IL-1 nor TNF significantly affected TIMP expression; 4) PMA induced both metalloproteinase and TIMP expression; and 5) the combination of IL-1 plus TNF had a synergistic effect on stromelysin expression. Dose response and time course experiments demonstrated that the synergistic effect of IL-1 plus TNF occurred at saturating concentrations of each cytokine and lasted for 7 days. In summary, the ability of IL-1 and TNF to preferentially induce stromelysin and collagenase expression, versus TIMP, may define a pivotal role for these cytokines in the pathogenesis of rheumatoid arthritis.
3230571	Gynecomastia as a complication of auranofin therapy.	1988 Dec	Gynecomastia was found in a patient taking 12 mg of auranofin (AF) daily. The gynecomastia was noticed after AF was increased to this dose and resolved after the drug was discontinued. The patient refused rechallenge.
2735962	Expression and regulation of the HLA-DR antigen on circulating monocytes isolated from pat	1989 Jun	Using a modified radioimmunoassay, surface labeling of HLA-DR antigens on monocytes revealed reduced densities in patients with active rheumatoid arthritis (RA) (P less than 0.001) and in gold-treated patients (P less than 0.01) versus normal controls. Significant enhancement of DR antigen expression (P = 0.01), with values similar to those of normal monocytes, occurred in patient monocytes preincubated at 37 degrees C overnight, but not in monocytes preincubated at 4 degrees C. This suggested that a temperature-dependent metabolic process is required to enhance antigen expression. The addition of cycloheximide totally inhibited the enhancement of DR antigen density. Incubation of monocytes with exogenous prostaglandin E2 (10(-5)M final concentration) caused a reduction of DR densities on control and on RA monocytes, although this decrease was more marked in the controls. Addition of indomethacin did not affect DR antigen levels on control monocytes, but greatly enhanced the expression of DR antigens on RA monocytes. When HLA-DR antigen levels were estimated in detergent-solubilized membrane preparations, monocytes from patients with active RA demonstrated normal-to-increased densities compared with control monocytes. Thus, although RA monocytes possess a normal ability to synthesize DR molecules, surface expression of these molecules is inhibited; this inhibition may be mediated by prostaglandin E2 acting as a negative suppressive signal.
2338453	Interleukin 2 (IL 2) inhibitor in rheumatoid synovial fluid: correlation with prognosis an	1990 Mar	A soluble activity inhibiting over 50% of the CTLL-2 cell line response to recombinant human interleukin 2 (IL 2) was found in 17 of 29 (59%) rheumatoid synovial fluids. To study the prognosis value of this activity, 16 rheumatoid synovial fluids were collected before a radiation synovectomy of the knee with 7 mCi of 90Yt. Patients with a good clinical result after the synovectomy had a lower IL 2 inhibitory activity than those with a bad or incomplete result (P less than 0.01). Levels of inhibitory activity and of soluble IL 2 receptors were correlated with each other and with the response of the synovitis to the radiation synovectomy. These results extend the clinical usefulness of soluble IL 2 receptor measurements and indicate a correlation between the immune activation of the rheumatoid synovitis and its clinical activity.
2926229	The pronator quadratus sign: its classification and diagnostic usefulness for injury and i	1989 Feb	The clinical value of the pronator quadratus radiological sign was investigated. Fresh undisplaced fractures of the distal radius and acute injuries of the distal radio-ulnar joint showed anterior displacement of the radiolucent shadow in 85% and 88% respectively, but normal subjects no displacement. In rheumatoid arthritis, the presence of synovitis of the wrist joint appeared to be correlated with a blurred shadow at the distal end.
1863825	Which patients see a rheumatologist? SWRACR (South Western Regional Advisory Committee on	1991 Aug	Rheumatology outpatient consultations were recorded throughout the South Western Regional Health Authority for one month. Of 2987 consultations (equivalent to 32,600 annually), 630 (21%) were new referrals who waited 60 days (mode) before their consultation. Rheumatoid arthritis and polyarthritis accounted for 43% of new referrals and 75% of follow-up patients. For these categories, 6.5 follow-up patients were seen for each new referral, but this ratio varied from 3.7 to 11.7. Other diagnoses also had variable patterns of follow-up but because they represented only a small proportion they were less relevant to overall service provision and resource consumption. These data not only outline current outpatient working patterns but also indicate areas of further investigation which might elucidate methods of providing good patient care and appropriate use of resources.
3070709	Immuno-electron microscopy of chondrocyte-derived cells in the rheumatoid cartilage-pannus	1988	Immuno-electron microscopy has been utilised to examine the cartilage-pannus junction in seven patients with rheumatoid arthritis. Using a monoclonal antibody, keratan sulphate was localised to cells with the ultra-structural appearance of fibroblasts within a transitional fibroblastic zone in the pannus in two cases. This confirms previous light microscopy evidence that this area (which is clearly separate from articular cartilage) contains cells which produce keratan sulphate, and strengthens the hypothesis that these cells are derived from cartilage rather than from the adjacent synovial membrane.
1671880	Night sedation and arthritic pain.	1991 Feb	This pilot study highlights the problems of benzodiazepine (BDP) usage in patients attending a rheumatology clinic. Of 127 consecutive patients attending the rheumatology clinic a total of 29% (37) had been taking night sedation for mean duration of 4.1 years. The majority of BDP users (92%) were women. In 78% night sedation was taken for insomnia associated with night pain. We recommend that if BDP is to be prescribed it should be only in selected cases for a short time.