Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2787670 | The microheterogeneity of desialylated alpha 1-antichymotrypsin: the occurrence of two ami | 1989 Jul 27 | ACT (alpha 1-antichymotrypsin), a serine antiproteinase with specificity against neutrophil cathepsin G, is homologous with alpha 1-antitrypsin, plasminogen activator inhibitor and angiotensinogen, all with known amino-terminal microheterogeneity. Here we report that the two predominant isoforms of desialylated ACT obtained on isoelectric focusing correspond to a microheterogeneity at the amino terminus of ACT: one isoform (His-Pro-Asn-Ser-Pro-) and a two residues shorter isoform (Asn-Ser-Pro-). The relative occurrence of the two isoforms was comparable both in normal plasma, acute-phase plasma and plasma from subjects with heterozygous familial ACT deficiency. When desialylated ACT, isolated by affinity chromatography from ACT-deficient, normal or acute-phase plasma, was compared with regard to mass and charge microheterogeneity, we found no significant differences in either respect. Nor was the isoform pattern of desialylated plasma from patients with rheumatoid arthritis different. Although the occurrence of heterozygous familial ACT deficiency implies genotypic variation, isolated ACT from patients with the trait was not found to exhibit any phenotypic variation detectable by standard electrophoretic methods. | |
| 2787714 | A transient rise in agalactosyl IgG correlating with free interleukin 2 receptors, during | 1989 Jun | The proportion of oligosaccharide chains on the Fc fragment of IgG which terminate with N-acetylglucosamine and not galactose (%GO) has previously been shown to be raised in rheumatoid arthritis (RA), Crohn's disease (CD) and tuberculosis (Tb), but to be normal in sarcoidosis (SA), and in both lepromatous and tuberculoid leprosy. However we have now studied %GO in sequential serum samples collected from lepromatous leprosy patients undergoing episodes of erythema nodosum leprosum (ENL). During ENL %GO is transiently raised, and this rise parallels an increase in circulating interleukin 2 receptors (IL-2R). These findings confirm that changes in T cell function occur during ENL. Moreover it appears that %GO rises when there is, simultaneously, T-cell-mediated tissue damage and an acute phase response (RA, CD, Tb, ENL), but not when there is an acute phase response without major T cell involvement, or chronic T cell activity alone (SA, and tuberculoid leprosy). We suggest therefore that %GO is an indicator of a type of T cell activity with broad immunopathological implications. | |
| 2787402 | Interleukin 2 and interleukin 2 inhibitors in human serum and synovial fluid. I. Character | 1989 Feb | An inhibitor of the murine interleukin 2 (IL-2) dependent cell line (CTLL-2) has been demonstrated in sera from healthy subjects as well as in sera and synovial fluid from patients with inflammatory arthritides. This inhibitor inhibits the mitogenic response of normal peripheral blood mononuclear cells and seems to be primarily due to impaired IL-2 production. The inhibitor does not appear to bind to IL-2 or the IL-2 receptor. This inhibition can be reversed with IL-2 but not interleukin 1. These observations may apply to the defects in IL-2 production and response demonstrable in rheumatoid arthritis and other autoimmune disorders. | |
| 2905552 | [Molecular genetic analysis of autoantibody production in systemic lupus erythematosus]. | 1988 Dec 2 | This review summarizes studies from our and other laboratories attempting to define the molecular and clonotypic origin of autoantibodies that typify systemic autoimmune diseases such as lupus and rheumatoid arthritis. Comparative restriction fragment length polymorphism (RFLP) studies investigating the immunoglobulin (Ig) germline gene organization in lupus-prone strains of mice suggested that the disease can develop in different Ig heavy (H) and light (L) chain haplotypes, and that the Ig germline genes in lupus mice are probably normal. Analysis of the Ig gene segments expressed in monoclonal autoantibodies from autoimmune mice revealed that similar, and in some instances even identical, gene segments are expressed in autoantibodies and in antibodies to exogenous antigens, and that anti-self and anti-non-self responses are encoded by the same, or at least an overlapping germline gene repertoire. A large variety of Ig variable (V), diversity (D), and joining (J) gene segments can encode autoantibodies with different specificities, and both germline genes and somatically-mutated genes can be expressed in such antibodies. | |
| 3170987 | Urine-histamine levels in patients with hereditary angioedema (HAE). | 1988 Sep | Hereditary angioedema (HAE) is defined clinically by recurrent, self-limited episodes of angioedema. The disease is defined biochemically by a deficiency in the functional activity of C1 esterase inhibitor. To date, the actual serum or tissue mediator(s) responsible for the angioedematous lesion remains controversial. Although antihistaminics have been clearly demonstrated to have no efficacy in the long-term treatment of this disorder, instances of elevated urine-histamine levels in patients with HAE raises the possibility of a role for histamine in the pathophysiology of this disease. Urine samples were collected from 28 asymptomatic and from 11 symptomatic patients with HAE. The urine-histamine levels were compared with levels of 41 normal control subjects. With the exception of one asymptomatic patient with HAE whose diagnoses also included rheumatoid arthritis and secondary Sjögren's syndrome, the urine-histamine levels from asymptomatic patients with HAE were similar to values obtained from normal control subjects. Except for data from two patients with HAE, urine-histamine levels from symptomatic patients with HAE were also indistinguishable from levels of normal volunteers. These data suggest that the vast majority of patients with HAE have normal urine-histamine levels both during and between attacks. Consequently, histamine is unlikely to play a pathophysiologic role in HAE. | |
| 3388313 | Fibrin configuration on glass led to decrease of neutrophil adherence in systemic lupus er | 1988 Mar 15 | Using a previously developed in vitro assay of glass adherence of neutrophils following blood clotting, we compared the results of new patients with systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA) and those of normal controls. In acute phase of the disease, all 33 patients (100%) of SLE, 2 of 35 patients (5.7%) with JRA had a significantly low neutrophil adherence to glass surface (less than 25% of the normal values). During 2 years follow-up in 18 patients with SLE from the onset of the disease, we consistently observed the low cell adherence during the relapses of the disease in all the patients. When remains of glass surfaces were examined under scanning electron microscope (SEM), we found a notable morphologic difference of fibrin configuration between the specimens of active SLE and normal controls. We conclude that the varied results of neutrophil adherence on glass may reflect the forming of different fibrin configuration induced by the in vitro contact system of coagulation. The findings may explain the increased thrombotic complications reported in patients with active SLE. | |
| 3174922 | Psychiatric and neurological manifestations in systemic lupus erythematosus. | 1988 Jan | The frequency and type of psychiatric disease were investigated in 40 patients suffering from systemic lupus erythematosus (SLE) and 27 control subjects with rheumatoid arthritis or inflammatory bowel disease. The psychiatric morbidity at the time of interview was the same in the two groups, but the patients with SLE had experienced more episodes of psychiatric illness in the past, and psychotic symptoms occurred only in this group. Half of the patients with SLE had previous or current evidence of neurological involvement; an association was found between neurological disease and psychotic symptoms in SLE, while anxiety and affective disturbances appeared to be closely related to environmental factors in both patients with SLE and controls. There was no correlation between psychiatric and neurological disease and clinical or laboratory indices of disease activity. Magnetic resonance imaging of the brain was performed in 15 patients with SLE. Abnormalities were more often present in those with neurological disease; no such correlation was found with psychiatric illness. | |
| 3072662 | Factors which influence the incidence and course of peptic ulcer. | 1988 | The present review concentrates on environmental factors which influence the outcome of peptic ulcer disease by acting from the outside. Endogenous risk factors, such as acid output, pepsin secretion and serum pepsinogen, gastritis and mucosal defense, blood group, and secretor status, are only dealt with when they help to explain the mechanism by which exogenous risk factors affect the upper gastrointestinal mucosa. After outlining the wax and wane of peptic ulcer, it is concluded that these changes resulted from similar temporal patterns of occupational workload in the general population. Cross sectional studies also support the contention of occupational workload being a risk factor in peptic ulcer, explaining several characteristic features of peptic ulcer, such as its sex, race, and social class distribution, increased incidence in immigrant workers, seasonal variation, healing by bed rest, and urban versus rural distribution. Susceptible subjects may react to a rise in occupational workload and acute exposure to stressful life events by increased gastric secretion which, in turn, leads to ulceration and symptoms. Cigarette smoking, intake of aspirin and related drugs, dietary salt, and alcohol abuse represent additional environmental risk factors, which form the etiologic link of the association of peptic ulcer with chronic lung disease, rheumatoid arthritis, hypertensive disease, and liver cirrhosis, respectively. | |
| 3615575 | Measurement of hand bone mineral content using single-photon absorptiometry. | 1987 Jun | A single photon absorption imaging technique has been developed to assess the bone mass of the hand, especially in patients with rheumatoid arthritis or bronchial asthma. A modified rectilinear scanner images the hand by transmission scanning in a water bath with a 7.4 GBq 125I source. A microcomputer is used to calculate the bone mineral distribution, and the total bone mineral content (BMC) of the hand is determined from that distribution. The precision (coefficient of variation) of the measurement is 1.9%. A control population of 20 men and 58 women has been studied to determine normal variations in hand bone mineral content with age, sex, body size, hand volume and years since menopause. The normal men are found to have an average hand BMC of 25.1 g with a coefficient of variation (CV) of 22%, which is reduced to 12% by normalising for body size using span. The normal women had an average hand BMC of 18.0 g +/- 15%. The CV is reduced to 13% by normalising for span and years post-menopause. | |
| 3552598 | Polymyalgia rheumatica. Its correct diagnosis and treatment. | 1987 Mar | Giant cell (temporal) arteritis was first described by Horton and colleagues in 1932, and polymyalgia rheumatica in 1957 by Barber who suggested this title for an entity resembling, but distinct from, rheumatoid arthritis of unknown aetiology in the elderly. Arteritic features were sufficiently common in polymyalgia rheumatica to suggest an arteriopathy as a cause, further evidence of this being the change from the clinical picture picture of polymyalgia rheumatica to giant cell arteritis and vice versa in many patients such that the alternative title polymyalgia arteritica was suggested. The clinical picture of polymyalgia rheumatica is that of an elderly patient, more often female than male, usually over 60 years of age, with painful stiffness in the girdle joints and muscles of the shoulders and hips, but seldom with findings in peripheral or intermediate joints. The painful stiffness in the shoulders, hips and thighs is worse in the early morning. An erythrocyte sedimentation rate over 50mm in 1 hour is usual, and there is a rapid and dramatic response to small doses of corticosteroids (around 10mg prednisolone daily). Arteritic and axial arthritic features have been noted by different authors in different ratios, the disorder gradually abating naturally over periods varying from several months to 7 to 10 years. Deaths, when they occur in this elderly group of patients, have usually been unrelated to the disease or its treatment, but osteoporotic vertebral crush fractures are not uncommon. Partial or complete blindness may occur in patients with either giant cell arteritis or polymyalgia rheumatica, often appearing rapidly after cessation of corticosteroid therapy or rapid reduction of dosage.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3333283 | Some unexplored regions of psychosomatic medicine. | 1987 | The history of psychosomatic medicine in the 20th century is predominantly marked by a concern with studies of major diseases (e.g., angina pectoris, bronchial asthma, diabetes mellitus, essential hypertension, neurodermatitis, rheumatoid arthritis, etc.). Traditional physicians also narrowly focus on disease--a trend that began with Morgagni in the 18th century. But disease (defined by structural alterations) is not the only cause of illness and disability. In fact, most persons seeking health care are ill without having a disease. It is only recently that this distinction has been fully made. The various manifestations of ill-health go by a variety of descriptive names--the functional or irritable bowel and hyperventilation syndromes, fibromyositis, psychophysiological, functional and somatoform or somatization disorders. They lead to loss of productivity, cost the health care system excessively, produce negative reactions in physicians, and are fertile ground for iatrogenic disease. They do not constitute discrete syndromes but overlap, each also being closely associated with anxiety and depression, sleep disturbances or marital disruption. They are the manifestations of sick persons not only of disturbances of bodily systems. They may be precipitated by unemployment, marital discord, bereavement, and job dissatisfaction. Curiously, ill-health has not been the major area of investigative interest of psychosomatic medicine. This presentation will emphasize why it should be, and why proper interventions may radically reduce the cost of medical care, prevent iatrogenic disease, and reduce the use of ill-advised procedures.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3559074 | Power staple fixation in hand and wrist surgery: new applications of an old fixation devic | 1987 Mar | After laboratory testing power driven staples were used in metaphyseal type bone 39 times from December 1983 through April 1985 in 33 patients with hand or wrist problems. Applications included arthrodeses, nonunions, and osteotomy fixation. Diagnoses included rheumatoid and degenerative arthritis, scaphoid, and interphalangeal nonunions. There were no infections, and only one staple has broken. There has been little evidence of loosening or inflammation. Shattering of bone has not occurred; osteoporotic bone appears to be ideal tissue in which to use this fixation. | |
| 3693417 | Basal joint implant arthroplasty in osteoarthritis. Indications, techniques, pitfalls, and | 1987 Nov | Implant arthroplasty is a valuable surgical procedure for some patients with basal joint arthritis of the thumb. Those patients for whom it seems to be the most useful are the low-demand osteoarthritic and the rheumatoid. Should this type of arthroplasty be selected, the associated soft tissue reconstruction is of paramount importance in determining the success of the surgical effort. | |
| 1970334 | Conservation of the central MHC genome: PFGE mapping and RFLP analysis of complement, HSP7 | 1990 | A degree of conservation of the genes located between class II and class I [central major histocompatibility complex (MHC) genes] is apparent among mammalian species including primates and the mouse. Few others have been analyzed. The caprine MHC is of particular interest, since it has recently been observed that susceptibility to a lentivirus-induced polyarthritis (caprine arthritis) segregates with serologically defined MHC class I antigens. This arthritis resembles, in a number of respects, rheumatoid arthritis in man. Human cDNA probes were used to examine the caprine central MHC and class I and II genes by restriction fragment length polymorphism (RFLP) and by pulsed field gel electrophoresis (PFGE) in order to define the polymorphism and linkage of central MHC genes to class I and class II genes. An outbred population of dairy goats (Saanen, British Alpine, Anglo Nubian, and Toggenberg) was examined for class I and class II RFLPs. Both regions were found to be highly polymorphic. The number of fragments hybridizing to an HLA-B7 probe after Eco RI, Bam HI, Bgl II, or Hind III digestion suggests there may be 10-13 class I genes. The degree of polymorphism was comparable to that reported in the mouse. Limited polymorphism was found in the central MHC genes. The caprine C4 and CYP21 genes were duplicated and demonstrated RFLP with Bam HI, Hind III, Eco RV, and Taq I. An infrequent Taq I C2 polymorphism was found. PFGE revealed substantial conservation of both the order and linkage of the central MHC genes when compared with mouse and man. C4, C2, CYP21, HSP70, and tumor necrosis factor (TNF) genes are all located within 800 kilobase (kb) of the class I loci. Distant from the class I region, the C4, C2, and CYP21 genes are linked on a short genomic segment (180 kb Not I and 190 kb Pvu I fragments). HSP70 cohybridizes with the complement genes on a 380 kb Mlu I fragment. Linkage of HSP70, TNF, and class I genes was found on a single Not I fragment (610 kb). TNF and class I cohybridize on Pvu I (730 kb) and Not I (610 kb) fragments. Conservation of a similar central MHC genomic structure across species argues for functional interaction between the central MHC genes. We postulate selection for these central MHC genes through their role as non antigen-specific regulators of immune response. | |
| 1851718 | Monocytoid B-cell lymphoma in patients with Sjögren's syndrome: a clinicopathologic study | 1991 May | A recent clinicopathologic study of a series of patients with monocytoid B-cell lymphoma (MBCL) indicated that there is a frequent association between MBCL and Sjögren's syndrome (SS) and raised the possibility of a relationship between these two disease entities. To further investigate the possible relationship of MBCL and SS, we studied pathologic and clinical characteristics of 13 patients with MBCL who had clinically documented SS. In all patients, the lymphoma had the characteristic morphologic features of MBCL, and immunologic and molecular hybridization studies confirmed the B-cell nature of the lymphoma. Twelve of the 13 patients were female, with a median age of 66 years at diagnosis. Eleven had localized disease and presented with either salivary gland or cervical lymph node enlargement; one patient presented with a breast mass, and another with generalized lymphadenopathy and hepatosplenomegaly. In five of 13 patients, the MBCL was associated with or progressed to large cell lymphoma. In two patients, there was bilateral involvement of the parotid gland; one had a synchronous high-grade lymphoma in both parotid glands. In two patients, bone marrow biopsies showed involvement by MBCL. Eleven patients are alive 2 to 55 months after the diagnosis of MBCL. One patient died with the disease 8 months after the initial diagnosis. Another patient died of an unrelated cause without evidence of disease 16 months after the diagnosis of MBCL. We conclude that there is a more than fortuitous association between MBCL and SS. This concept is consistent with previously reported observations of reactive monocytoid B cells in patients with benign lymphoepithelial lesions of salivary glands, which may result from selective homing of reactive monocytoid B lymphocytes to the benign lymphoepithelial lesions and their subsequent neoplastic transformation. | |
| 2789658 | Autoantibody synthesis in salivary glands of Sjögren's syndrome patients. | 1989 Aug | We investigated the possibility that autoantibodies are locally synthesized and secreted within salivary glands of patients with Sjögren's syndrome by measuring specific autoantibody as a proportion of the total immunoglobulin present both in serum and saliva. Of 25 patients studied, 21 showed salivary enrichment of IgA anti-La, in three cases IgA anti-La being detected in saliva when IgG anti-La was negative (by ELISA) in serum. Twenty-four showed enrichment of salivary rheumatoid factors and IgA and/or IgM carrying the 17-109 idiotype, a marker of kappa IIIb light chains. These data suggest that autoantibodies, especially of the IgA class, are synthesized primarily in salivary gland and that they can be detected in saliva before they become apparent in the peripheral circulation. The subsequent deposition of these antibodies within salivary glands may be a contributory factor to the pathogenesis of Sjögren's syndrome. | |
| 2474646 | Epithelial HLA-DR expression in labial salivary glands in Sjögren's syndrome and non-spec | 1989 Mar | The expression of the Class II major histocompatibility antigen HLA-DR was quantified in the epithelial cells of labial salivary glands from patients with Sjögrens Syndrome (SS) and compared with similar expression in glands showing non-specific sialadenitis and normal controls. In all glands more duct cells were positive than acinar cells but only in sialadenitis and SS was strong epithelial staining seen. The proportions of duct and acinar cells expressing HLA-DR were increased between normals and sialadenitis (P less than 0.01) and between sialadenitis and SS (P less than 0.001). However, for all cases increased expression of HLA-DR correlated to the increased proportion of inflammatory cells in the gland (P less than 0.01). The results indicate that although HLA-DR is expressed on the epithelial cells in the glandular lesions of SS, this is not specific as it is also seen in sialadenitis. This supports the view that such expression is secondary to an inflammatory infiltrate and may not be of importance in initiating autoimmune tissue damage. | |
| 3497597 | [Acrosclerosis, Gougerot-Sjögren syndrome, myxedema and anti-centromere antibodies. 3 cas | 1987 | The authors report three identical cases of the association of acrosclerosis with telangiectasis without calcinosis, Sjögren-Gougerot syndrome, myxoedema with antithyroid antibodies and anti-centromere antibodies. The association of these conditions one with another has already been published, but, to the authors' best knowledge, this is the first report of all of them grouped together in the same patients. With reference to the literature, the authors discuss the problems of individualization of the CRST syndrome and its varieties and the clinical significance of the presence of anti-centromere antibodies. | |
| 1720958 | Autoimmunity to human thyroglobulin. Respective epitopic specificity patterns of anti-huma | 1991 Dec | We evaluated the epitopic specificity pattern of anti-human thyroglobulin (anti-hTg) autoantibodies from patients with primary Sjögren's syndrome (SS). All of the primary SS sera tested contained both IgG and IgM anti-hTg autoantibodies recognizing at least 1 region on hTg; in 65% of the cases, 3 or more regions were recognized. A strong recognition of region II, as is seen in Hashimoto's thyroiditis, was associated with thyroid disorder in primary SS. These results emphasize the importance of region II in autoimmune thyroid disease. | |
| 3378123 | Neutropenia and infections in Felty's syndrome. | 1988 Jun | Fifteen patients with Felty's syndrome (FS) were studied prospectively during a 3-year period to determine the influence of multiple haematologic parameters on the incidence of infections. An increased risk of recurrent major and minor infections was primarily related to peripheral blood polymorphonuclear cell (PMN) counts of less than 0.1 x 10(9)/l. Bone marrow lymphocytosis, a decreased percentage of PMN in bone marrow differential counts and an impaired in vitro growth of colony-forming unit-PMN macrophage were also related to an increased incidence of infection but were predominantly present in patients with less than 0.1 x 10(9)/l circulating PMN. The maximal response in the number of circulating PMN measured after injection of epinephrine and hydrocortisone varied substantially within patients, but those with less than 0.1 x 10(9)/l PMN always had lower responses than those with greater than 0.1 x 10(9)/l PMN. These variables did not therefore contribute to the identification of FS patients at risk of infection. |