Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1152671 | Amyloidosis: review of 236 cases. | 1975 Jul | From 1960 through 1972, 236 cases of amyloidosis with histologic proof were found. The amyloidosis was primary (without evidence of preceding or coexisting disease) in 132 cases (group 1) and associated with multiple myeloma in 61 (group 2). Secondary amyloidosis appeared in 19 cases (associated with rheumatoid arthritis or osteomyelitis in two-thirds of them). There were 22 patients with amyloid localized to a single organ (bladder, lung, skin, or larynx in more than half of them). Two patients had familial amyloidosis. In group 1 and group 2, the most common presenting symptoms were fatigue, weight loss, edema, dyspnea, light-headedness or syncope, and paresthesias. Symptoms of the carpal-tunnel syndrome were frequent. The liver was palpable in almost 50% of the series, but splenomegaly was an initial finding in less than 10%. Macroglossia was recorded in 26% of group 2 and in 12% of group 1. Enlargement of submandibular structures was noted in about 10% of cases; and purpura, particularly around the eyes, was a significant feature. Substantial numbers of the patients had carpal-tunnel syndrome, nephrotic syndrome, congestive heart failure, sprue, peripheral neuropathy, or orthostatic hypotension. Approximately 50% of patients had renal insufficiency at the time of diagnosis. Proteinuria was found in more than 90%. A monoclonal protein was found in the serum of 49% of group 1 and in 74% of group 2. Monoclonal proteins were found in the urine of 35% and 81%, respectively. Only 12% of patients in group 1 had no monoclonal protein when both serum and urine were analyzed, and all patients of group 2 had a monoclonal protein in the serum or urine when both were analyzed. Lambda light chains were more common than kappa. None of the patients in group 1 had more than 15% plasma cells in the marrow, whereas more than half of group 2 had more than 15% plasma cells. Roentgenograms showed no evidence of skeletal disease in 94% of group 1, but 50% of group 2 had skeletal abnormalities. Rectal biopsy was positive for amyloid in 84% of cases. Kidney, liver, and carpal-tunnel biopsies were positive in 90% or more. Follow-up of all 193 patients in groups 1 and 2 revealed that 80% of group 1 and 97% of group 2 had died. The median survival was 14.7 months in group 1 and 4 months in group 2. Cardiac failure was the most common cause of death, accounting for 30% of the fatalities. We also reclassified all cases by the method of Isobe and Osserman (105), which is based on clinical patterns: pattern I--principal involvement of tongue, heart, gastrointestinal tract, muscle, nerves, skin, and carpal ligaments; pattern II--principal involvement of liver, spleen, kidneys, and adrenals; and mixed pattern I and II. This analysis failed to reveal predictive value in the clinical pattern classification, and did not discern the survival differences between primary amyloidosis (group 1) and amyloidosis with myeloma (group 2). Consequently, for the present we prefer the classification used in this study. | |
| 12339971 | [Current issues in contraception]. | 1985 Feb | ||
| 3873410 | Null alleles of the fourth component of complement and HLA haplotypes in familial systemic | 1985 | Eight families (121 individuals) with two or more members affected with systemic lupus erythematosus (SLE) were analyzed for histocompatibility antigens (HLA-A, B, C, DR, MT, and MB) and complement antigens (C4A, C4B, and BF). These data were correlated with serological markers (antinuclear antibodies, single- and double-stranded anti-DNA, anti-SM, anti-nRNP, anti-Ro [SS-A], anti-La [SS-B], and biological false-positive tests for syphilis and clinical features. Fifteen members had SLE, and 19 had other immune diseases (subacute cutaneous lupus erythematosus, discoid lupus erythematosus, hypothyroidism, insulin-dependent diabetes mellitus, primary Sjogren's syndrome, immune thrombocytopenic purpura, rheumatoid arthritis, and multiple sclerosis). Twenty-three healthy relatives (seroreactors) had significant titers of circulating antibodies, as did 2 of 17 spouses. There was an increased frequency of null C4 alleles in those individuals with SLE (60%) and healthy relatives (50%) as compared with spouses (24%). Multivariate analysis showed a significant association between SLE and female sex (P =.006), whereas there was no significant association revealed between female sex and other immune diseases. Patients with SLE also had a higher frequency of either C4A or C4B null alleles (P = .01) than those with immune diseases. The C4A homozygous null phenotype was more common in SLE patients than in seroreactors (P = .02). There was a higher frequency of HLA-DR2 and DR3 in individuals with SLE than in those with immune disease (P = .08), seroreactors (P = .02) and normal relatives (P = .002). One totally C4-deficient patient with SLE was identified. These families demonstrate an important association between SLE and the C4 null allele and the HLA-DR2 and DR3. These risk factors, however, cannot account for the development of disease in all individuals. | |
| 6189861 | In vitro nucleoside specific immune response by lymphocytes from systemic lupus erythemato | 1983 May | The in vitro immune response of systemic lupus erythematosus (SLE) lymphocytes to nucleosides conjugated to keyhole limpet hemocyanin (KLH) (A,G,C,T-KLH) was investigated. The nucleosides were chosen not only because they are a part of nucleic acid antigen and involved in autoimmunity, but also because nucleoside covalently bound to either soluble IgG or cells had been shown to induce unresponsiveness in mice. A significant proliferation index was induced in SLE lymphocytes, as compared with normal or rheumatoid arthritis (RA) lymphocytes in vitro [in (A,G,C,T)-KLH, 1 microgram/ml; stimulation index = M +/- SE, SLE 2.10 +/- 0.26, RA 1.06 +/- 0.14, normal 1.12 +/- 0.12 P less than 0.05]. Lymphocytes from SLE patients responded specifically to low doses of (A,G,C,T)-KLH and not to the protein carrier KLH alone. A solid-phase radioimmunoassay was developed to detect nucleoside-specific antibody. SLE lymphocytes spontaneously produced high levels of anti-A,G,C,T antibody. This was further increased by antigenic stimulation, but not with pokeweed mitogen (PWM) stimulation. In contrast normal lymphocytes failed to produce anti-A,G,C,T antibody either spontaneously or in response to antigen. However, normal lymphocytes produced antibody after stimulation with PWM. More importantly, anti-A,G,C,T antibody production by SLE lymphocytes was suppressed by preincubation with A,G,C,T-IgG (A,G,C,T-HGG). The antigen-specific unresponsiveness caused by A,G,C,T-HGG was demonstrated by the observation that preincubation with A,G,C,T-HGG did not affect the production of anti-dinitrophenyl antibody response. The ability to manipulate the altered response of SLE lymphocytes to nucleic acid antigens may have therapeutic implications in these patients. | |
| 6283846 | Mediation of leukocyte components of inflammatory reactions by lipoxygenase products of ar | 1982 | The leukocyte lipoxygenase products LTB4 and 5-HETE elicit human neutrophil and eosinophil chemotactic responses in vitro and in vivo (Fig. 4), and are present at elevated concentrations in the lesions of some human inflammatory diseases, such as rheumatoid arthritis and the spondyloarthritides. The chemotactic potency of LTB4 is similar to that of the minor fragment of the fifth component of human complement, termed C5a, and is 30- to 300-fold greater than that of 5-HETE and of other natural DHETE isomers. Human neutrophils possess distinct subsets of chemotactic factor receptors that are specific for LTB4 and for 5-HETE, as demonstrated by the selective competitive inhibition of the chemotactic responses to the parent stimuli by acetyl LTB4 and 5-HETE methyl ester, respectively, and by the failure of the lipid chemotactic factors to bind to isolated membrane protein constituents of the human neutrophil receptors for chemotactic formyl-methionyl peptides. LTB4 and 5-HETE also elicit human neutrophil and eosinophil chemokinesis, stimulate the uptake of calcium and D-glucose, and enhance the expression of C3b receptors on the leukocytes; however, they exert only a minimal effect on superoxide generation and lysosomal enzyme release. LTB4, but not 5-HETE, stimulates the release of calcium from previously unexchangeable intraneutrophil pools, as has been described for potent peptide chemotactic factors. Although far less potent than LTC4 and LTD4, LTB4 constricts peripheral airways, enhances mucous secretion in the airways of the lung, and dilates and enhances the permeability of the microvasculature in skin and other organs (Fig. 4). A variety of leukocyte functions, including chemotaxis, D-glucose uptake, and lysosomal enzyme release, are impaired in association with the depletion of endogenous lipoxygenase products. Exogenous 5-HETE reverses some of the functional deficits of HETE-depleted leukocytes. Inhibition of leukocyte lipoxygenase activity also suppresses the intracellular content of hydroperoxyeicosatetraenoic acids and of novel polar metabolites of arachidonic acid that may be critical to the activation of human neutrophils and eosinophils. Thus LTB4 and the less potent 5-HETE are active extracellular mediators of the leukocytic components of hypersensitivity and inflammation and may also serve an important role as intracellular mediators of leukocyte function. | |
| 6283001 | Correlation of in vitro and in vivo effects of gold compounds on leukocyte function: possi | 1982 Jul | The anti-inflammatory effects of gold compounds include suppression of PMN lysosomal enzyme release. Since lysosomal products can provoke PMN aggregation, we assessed the effect of two gold compounds, auranofin and GST, on suppressing aggregation, degranulation, and metabolic functions of the cells. Aggregation of 1 x 10(7) cytochalasin B-treated PMNs in response to 2 x 10(-7)M FMLP, as assessed by light scattering, was inhibited in a dose-dependent fashion by both drugs. Concentrations of auranofin ranging from 5 to 20 microM caused 30.8% to 89% inhibition, whereas 200 microM GST reduced aggregation by only 32%. FCS or BSA added to suspensions of normal PMNs considerably reduced the gold compound inhibitory effect on PMN aggregation. Cell viability assessed by dye exclusion and lactate dehydrogenase release was unaffected by the drugs. The suppressive activities of the drugs could not be removed by washing the PMNs. Correspondingly, the drugs suppressed lysosomal enzyme release induced by FMLP of PMNs rendered secretory with cytochalasin B. Concentrations of 20 microM auranofin and 200 microM GST resulted, respectively, in a 61.5% and 19.3% reduction of release of lysozyme, 61.7% and 27.1% reduction of beta-glucuronidase, 84.8% and 33.7%s reduction of myeloperoxidase, and 50.0% and 25.0% reduction of lactoferrin. Furthermore, auranofin inhibited 14C-1-glucose oxidation through the hexose monophosphate shunt in response to stimulation by either PMA or methylene blue. The in vivo studies suggested that auranofin could prevent neither neutropenia induced by zymosan-activated serum nor a corresponding rise in plasma lactoferrin levels. These findings suggest that the beneficial effect of gold compounds in rheumatoid arthritis are unlikely to be related to their ability to dampen PMN activation in vivo. | |
| 6994615 | Effectiveness and risks of contraception. | 1980 | ||
| 6321576 | Microbial pathogenicity in oral soft tissue diseases. | 1984 Mar | Recent work implicating microbial factors in the pathogenesis of several oral soft tissue diseases is discussed. These conditions include recurrent aphthous ulceration, oral cancer, Sjogren's syndrome, and the oral lesions of AIDS (the acquired immune deficiency syndrome). This paper reviews some recent work on these topics, with emphasis on investigations in our laboratory. | |
| 371848 | Phytohemagglutinin (PHA) skin test. Characterization of immunological properties and clini | 1979 Mar | Immunological properties of phytohemagglutinin (PHA) skin reaction were investigated by animal and clinical experiments. In the guinea pigs an intradermal dose of PHA-P produced erythema and induration with a maximal response at 24 hours after the injection. Histologically it was characterized by perivascular infiltration of lymphoid cells in the dermis and subcutis, being similar to that of tuberculin (PPD) skin reaction. PHA skin reaction, however, showed some difference from that of PPD in the initial cellular response in that the former was composed of small mononuclear cells and granulocytes with rapid development and the latter was composed of large mononuclear cells (macrophages) and granulocytes with slow development. Intradermal injection of 1:1000 dilution of PHA-P produced a similar erythema in man. In 39 of 59 patients with connective tissue diseases, the results of the in vivo (skin test) and in vitro (lymphocyte transformation) response to PHA correlated well. In the 59 patients, the incidence of the positive rate of the PHA tests (55.9%) was significantly higher than that of the DNCB test (33.9%) and of the PPD test (23.7%). These observations suggest that the PHA skin test has properties of delayed hypersensitivity and is highly sensitive and that it may be a useful measure of cell-mediated immunity. | |
| 409821 | Immunopathology of Sjögren-like disease in NZB/HZW mice. | 1977 Sep | In vitro responsiveness of spleen cells from NZP/NZW (B/W) female mice, aged 2 through 40 weeks, to the mitogens phytohemagglutinin (PHA), concanavalin-A (Con-A) and lipopolysaccharide (LPS) was determined. An age-related decline in proliferative response of splenic cells was found; this decline correlated with the age of onset and progression of lymphoid infiltration in lacrimal and salivary glands in the mice. The worsening with age of this lymphoid infiltrate, coupled with the decline in responsiveness to mitogens, suggests a complex immunopathologic process with destruction of glands terminating in a disease similar to the Sjögren syndrome in humans. | |
| 322838 | Malignant lymphomas of the thyroid: a clinical pathologic study of 35 patients including u | 1977 Apr | The clinical and pathologic findings for 35 patients with malignant lymphoma presenting in the thyroid are reviewed. The lymphomas tended to occur in females with a median age of 65 years and clinically were manifested by a mass in the neck. The majority of patients were euthyroid and thyroid scans demonstrated cold nodules. In none of the patients was there clinical suspicion of lymphoma prior to surgery. Thirty-four of the cases were histiocytic lymphomas; the one exception; a patient with nodular poorly differentiated lymphocytic lymphoma, had histiocytic lymphoma in a subsequent biopsy of the soft tissues of the neck. Although classified as histiocytic, the lymphomas had the histologic and ultrastructural features of transformed lymphocytes or immunoblasts. Lending possible additional credence to the immunoblastic nature of these lymphomas was the histologic documentation of chronic lymphocytic thyroiditis in all 27 cases where residual thyroid parenchyma remained. This relationship suggests possible evolution of thyroid lymphomas from chronic lymphocytic thyroiditis and probably is analogous to the malignant lymphomas developing in other altered immune states, including Sjogren's syndrome. In the current study the overall 5-year survival was 54%. Patients under age 65, without local soft tissue extension or regional lymph node involvement, and with stage I disease survived the longest; a nodular histologic pattern also appeared to favorably influence the prognosis. Improved staging procedures and newer modes of therapy appear essential, particularly for those patients with clinical stage II disease and with local extension to soft tissues. | |
| 6352457 | Benign lymphoid disorders of the lung, with a theory regarding their development. | 1983 Oct | The authors review the clinical, radiographic, and pathologic features of the benign pulmonary lymphoid disorders. The essential role of immunopathologic techniques in distinguishing pulmonary lymphoid hyperplasias from malignant lymphoma is stressed. A theory regarding the development of pulmonary lymphoid hyperplasia is proposed as a basis for understanding these disorders. The authors suggest that lymphoid hyperplasia is a basic inflammatory response of the lung. | |
| 3972503 | The presence of cytotoxic autoantibody to lacrimal gland cells in NZB/W mice. | 1985 Feb | New Zealand Black and White F1 hybrid mice (NZB/W mice) spontaneously develop an autoimmune disease which provides us with a suitable animal model for Sjögren's syndrome. With increasing age, these mice develop foci of mononuclear cell infiltration in the lacrimal and salivary glands, which closely resemble the lesions seen in patients with Sjögren's syndrome. We studied the cell-mediated and antibody-mediated immune responses of NZB/W mice to lacrimal gland cells. Lacrimal gland acinar cells were isolated from 2-month-old NZB/W or BALB/c mice for the target of 51Cr-release assay. There was no statistically significant difference in the spleen cell-mediated cytotoxicity to lacrimal gland cells among NZB/W mice of different ages (2, 5, and 8 months old). With increasing age, on the other hand, we found a statistically significant increase in the titers of autoantibodies to lacrimal gland cells in NZB/W mice, while aged BALB/c mice did not develop such antibodies. Fractionation of pooled positive sera by gel filtration revealed that this cytotoxic activity was mostly recovered in the IgM fraction. The tissue absorption study showed that these antibodies cross-reacted with salivary gland and kidney. | |
| 6232211 | A strong association between the antinuclear antibody anti-La (SS-B) and the kappa chain a | 1984 | The distribution of immunoglobulin allotypes of the Gm and Km systems was examined in 51 patients with antinuclear antibodies (ANA), which reacted with two saline-extractable non-DNA nuclear antigens, anti-La (SS-B) and anti-RNP, which characterize certain multisystem autoimmune diseases. Forty-six percent of the 26 patients with anti-La were positive for the Km(1) allotype compared with 14% of the 35 with anti-RNP and 16% of 1204 of healthy subjects (corrected P value less than 0.005). The high frequencies of the Km(1) allotype (46%), female sex (100%), and the HLA-B8, DR3 phenotype (greater than 90%) in patients with anti-La are indicative of a substantial inherited predisposition to the development or expression of this autoantibody. The strong association between the Km(1) allotype and the anti-La response may be due to linkage disequilibrium between genes coding for the constant region of immunoglobulin kappa light chains and genes coding for the variable regions of kappa light chains which confer antibody specificity for the special configuration of the ribonucleoprotein known as La. | |
| 358992 | Identification and characterization of two new soluble nuclear antigens reactive with sera | 1978 Sep | Two antigens, temporarily referred to as MU and TM antigens after the original serum, that are closely related to the nucleolus have been identified in the nuclear soluble extract. Both antigens reacted with the sera of a small number of patients with various connective tissue diseases, and both were different from antigens described previously in these disorders. MU antigen was sensitive to the digestion with RNase and trypsin, and was shown to be equivalent to the nuclear ribosomal components in the nuclear extract. TM antigen was resistant to the digestion with RNase and trypsin, and was localized in the nucleolus and extranucleolar portion of nuclei, but the precise nature of TM has not been established. | |
| 3898477 | Clinical manifestations of dry eye states. | 1985 | Diagnosis of a dry eye is facilitated by prompt recognition of pertinent signs and symptoms and by utilisation of those office and laboratory procedures which help to confirm the diagnosis. Prior knowledge of those systemic diseases associated with keratoconjunctivitis sicca (KCS) alert the practitioner to a possible dry eye state. Conversely, a diagnosis of KCS may prompt recognition of a hitherto unsuspected systemic disease. In this review, I will discuss the signs and symptoms of KCS, its association with various systemic conditions, as well as the tests and procedures that contribute to its diagnosis. | |
| 343590 | Immune suppression of hematopoiesis. | 1978 Feb | Recent evidence suggests that immune mechanisms can injure proliferating hematopoietic precursor cells in the bone marrow. These may involve either humoral antibody or cell-mediated cytotoxic mechanisms. Immune injury can result in a variety of bone marrow failure syndromes. Immunologically induced abnormalities or blood cell production may be restricted to a single series, such as erythrocyte or granulocyte precursors, or may involve several hematopoietic lines; clinical manifestations reflect the cell line or lines that are injured. Immune suppression of hematopoiesis has now been described in pure red cell aplasia, immune panleukopenia, systemic lupus erythematosus, atypical cases of aplastic anemia and miscellaneous other hematologic diseases. | |
| 3871616 | Immunogenetic studies of juvenile dermatomyositis. III. Study of antibody to organ-specifi | 1985 Feb | Ninety children with definite juvenile dermatomyositis (JDMS), who had been HLA typed, were tested for the presence of tissue or organ-specific antibodies. Sixty had active disease at the time of study. The mean disease duration was 4 years, and 30 had soft tissue calcifications. The following autoantibodies were sought: thyroid, gastric parietal cells, smooth muscle, striated muscle, microsomes, mitochondria, DNA, extractable nuclear antigen, Sm, PM-1, antinuclear antibody (ANA), and rheumatoid factor. Only the ANA and PM-1 were more frequent in patients than in controls (P less than 0.0002 and P less than 0.001, respectively). Higher levels of immune complexes (P less than 0.01) were found in sera from patients with JDMS than in sera from controls and were correlated with the presence of ANA in patients (P less than 0.01). Soft tissue calcification was not associated with any autoantibody or HLA antigen, but with disease duration and activity (P less than 0.001 and P less than 0.05, respectively). There was no association between the occurrence of any autoantibody and the presence of HLA-B8 or DR3 among the white patients with JDMS. The frequency of autoantibodies in 43 full siblings of children with JDMS was not increased. We conclude that children with JDMS, with or without HLA-B8/DR3, do not show evidence of a generalized nonspecific antibody response to tissue antigens. The significance of the increased antibody to nuclear antigens ANA and PM-1 remains to be determined. | |
| 377267 | Primary biliary cirrhosis as a collagen disease. | 1979 Jun | Primary biliary cirrhosis is a disease of the small bile ducts with altered immunologic responsiveness often associated with various collagen diseases. All appear to be mediated by immune complex deposition. They probably are all different clinical manifestations of the same disease with different expressions determined by genetic and acquired factors. Therapy should be directed to the most immediate life-threatening problem. | |
| 833253 | Successful immunosuppressive therapy in insulin resistant diabetes caused by anti-insulin | 1977 Jan | A 45-year-old, non-obese female patient with no previous history of insulin administration was found to have extreme insulin resistance and abnormally high plasma immunoreactive insulin in the absence of anti-insulin antibodies in the serum. Clinically, there was no ketonuria. The patient also had evidence of Sjogren's syndrome with several immunologic features including hypergammaglobulinemia, positive antinuclear antibodies, accelerated erythrocyte sedimentation rate and leukopenia. Plasma pancreatic glucagon and C-peptide were elevated, but other endocrinologic abnormalties were not present. In this patient the insulin resistance appeared to be due to anti-insulin receptor antibodies which could be detected even in 1:500 dilution of serum. Immunosuppressive therapy with prednisolone and cyclophosphamide resulted in a decreased level of serum gamma globulin and a concomitant decrease of blood glucose level. After immunosuppressive therapy for eight months, the diabetic syndrome disappeared completely and anti-receptor antibodies in the serum were no longer detectable. Furthermore, insulin sensitivity returned to normal. However, the patient's glucose tolerance deteriorated after the temporary termination of cyclophosphamide treatment and the lowering of prednisolone dosage. |