Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3876375 | Production of interleukin 2 (IL 2) by salivary gland lymphocytes in Sjögren's syndrome. D | 1985 Nov | Because abnormalities in interleukin 2 (IL 2) production have been reported in the blood of patients with certain autoimmune diseases, we have examined the lymphocytes from patients with Sjögren's syndrome (SS) in which it is possible to obtain simultaneous samples of inflammatory site (i.e., salivary gland) lymphocytes and blood lymphocytes. We found that IL 2 production by peripheral blood lymphocytes (PBL) after mitogen stimulation was markedly diminished (4 +/- 2 U/ml) in 8/32 SS patients. However, salivary gland lymphocytes (SGL) from six out of six SS patients (including three patients with low IL 2 production by their PBL) had a high level of IL 2 production (97 +/- 32 U/ml), suggesting that IL 2 production by inflammatory site lymphocytes may differ from blood lymphocytes in the same patients. Low IL 2 production by a patient's PBL was not correlated with the patient's age, duration of disease, immunoglobulin level, or presence of antinuclear antibodies. Low IL 2 production was associated with a decreased ratio of Leu-3a/Leu-2a positive cells (p less than 0.05) and with an increased proportion of "activated" T cells expressing HLA-DR and gp140 (p less than 0.05). To determine the proportion of PBL and SGL containing cytoplasmic IL 2-like material, we used affinity-purified rabbit antibodies prepared against chemically synthesized peptides of human IL 2. Before mitogen stimulation, PBL were not stained by these antibodies (less than 1% reactive cells), whereas SGL T cells eluted from the salivary gland of SS patients contained a small (3.4% +/- 1.8) proportion of reactive cells. A similar proportion (2.4% +/- 1.2) of reactive cells was noted when frozen tissue sections of salivary gland biopsies were examined with these antibodies. After mitogen stimulation, 35% +/- 17 of PBL and 56% +/- 18 of SS SGL were specifically stained with anti-IL 2 peptide antibodies. In summary, these studies demonstrate a significant difference in IL 2 production between PBL and SGL of the same patients. Furthermore, antibodies against IL 2 peptides provide a powerful tool for detection of T cells producing IL 2 in vitro and in situ, and for understanding the role of this lymphokine in pathogenesis. | |
| 6601716 | Lymphocyte subsets in Sjogren's syndrome: a quantitative analysis using monoclonal antibod | 1983 Feb | Lymphocyte subsets in the peripheral blood of 18 patients with Sjogren's syndrome (SS) were studied using monoclonal antibodies and the fluorescence-activated cell sorter (FACS). The percentage of T cells was decreased when compared to normal controls. In primary SS, there was a proportional decrease in both suppressor/cytotoxic (anti-Leu-2a reactive) and helper/inducer (anti-Leu-3a reactive) T cells with an unchanged helper/suppressor ratio (1.8 vs. 1.7 for normals). In SS with an associated connective tissue disorder, there was a significant decrease only in the suppressor/cytotoxic subset. There was increase in B cells and null cells in primary SS compared to controls. Quantitative immunofluorescence allowed the calculation of determinant density per cell. Cells expressing low antigen density Leu-2a were increased in 8 patients (4 with primary SS and 4 with SS with an associated disorder). Thus, in addition to quantitative changes in lymphocyte subsets, we found changes in Leu-2a expression suggesting abnormal differentiation of the suppressor/cytotoxic subset. These changes may contribute to the immunoregulatory disturbance in Sjogren's syndrome. | |
| 6134267 | Studies of autologous mixed lymphocyte reactions in patients with systemic lupus erythemat | 1983 Jan | The autologous mixed lymphocyte reaction (AMLR) measures the proliferative response of peripheral blood T cells to surface antigens of non T cells. The AMLR of SLE patients with active or inactive disease either with (13) or without (6) immunosuppressive treatment was low compared with age and sex-matched controls, confirming previous reports. Only one patient with inactive, untreated SLE and one with drug induced lupus (procainamide) showed normal AMLR. Autologous reactivity was also reduced in 2 patients without treatment who presented with clinically complex disease syndromes, including primary biliary cirrhosis, or polyarteritis nodosa, together with Sjögren's syndrome and serological evidence of lupus. The AMLR could not be increased by changing the ratio of responder to stimulator cells. Patients with decreased AMLR also showed a decreased response to phytohemagglutinin which suggested a general depression of T cells. There was no correlation between the decreased AMLR and age, clinical features or anti-DNA antibody levels of the patients. In allogeneic mixed lymphocyte reactions (MLR) it was shown that non-T cells from SLE patients were poorer stimulators of allogeneic T cells than normal cells, and T lymphocytes from SLE patients were poorer responders to allogeneic non-T cells than were normal T cells. Both effects were much more marked in patients with active disease than in those with inactive SLE. This suggests a defect in both responder and stimulating cell populations in SLE. | |
| 6332630 | Elevation of von Willebrand factor is independent of erythrocyte sedimentation rate and pe | 1984 Sep | Von Willebrand factor (vWF) antigen levels were measured in 39 patients with biopsy-proven giant cell arteritis (GCA), 16 patients with polymyalgia rheumatica (PMR), 12 patients with Sjögren's syndrome, and 7 with choroiditis, as well as in 20 age- and sex-matched controls. Among GCA patients, 31 (group A) had clinically inactive disease and were taking low-dose glucocorticoids for at least 1 year; their vWF levels were high even in the presence of a normalized erythrocyte sedimentation rate (ESR). When the ESR and vWF were analyzed in another 8 GCA patients (group B) before and after treatment with glucocorticoids, vWF remained elevated even though the ESR returned to normal. Among the highest levels of vWF were those of 3 GCA patients who presented with ocular symptoms and positive temporal artery biopsies, but normal ESR. The presence of elevated vWF was not specific for GCA since elevated levels were also found in patients with PMR, Sjögren's syndrome, and choroiditis. The levels of vWF in GCA were significantly higher (P less than 0.01) than in these other conditions associated with myalgias and eye symptoms. Elevation of vWF levels may help in the differential diagnosis of GCA, particularly when the ESR is normal and ocular symptoms are present. | |
| 6768634 | Primary biliary cirrhosis: the prevalence of hypothyroidism and its relationship to thyroi | 1980 Jun | A survey of thyroid function in 95 patients with primary biliary cirrhosis revealed the presence of thyroid antibodies in 24 females and 1 male. Thirteen (52%) of this thyroid antibody positive group (all female) had biochemical evidence of thyroid disease: 8 (32%) were hypothyroid (7 of whom showed signs of myxedema), 2 had elevated thyroid stimulating hormone (TSH) levels, and 3 had abnormal responses to stimulation with thyrotropin releasing hormone (TRH). In contrast, only 3 (4%) of the thyroid antibody negative patients had reduced serum thyroxine (T4) levels and none were clinically hypothyroid. Evidence of an increase in thyroid hormone binding, as reported by other workers, was not found, and both the resin uptake of radioactive triiodothyronine and the free thyroxine indices were normal in both groups. The presence of thyroid antibodies showed a highly significant association with lacrimal gland dysfunction but not with liver histologic staging or liver function tests. | |
| 6286011 | Analysis of T lymphocytes after bone marrow transplantation using monoclonal antibodies. | 1982 Sep | Using monoclonal antibodies to cell surface antigens and fluorescent cell sorter analysis, we studied peripheral blood lymphocyte subsets after bone marrow transplantation (BMT). In 13 patients studied 3 mo or more after BMT, the ratio of T-cell subsets defined by antibodies OKT4 and OKT8 was reversed (OKT4/OK%8 = 0.7 +/- 0.3) in comparison to normal volunteers or bone marrow donors (ratio OKT4/OKT8 = 1.7 +/- 0.4) (p less than 0.001). This reversed ratio persisted for up to 3 yr after BMT. In contrast to a previous report, presence of an abnormal ratio of T-cell subsets did not correlate with clinically significant graft-versus-host disease (GVHD). In agreement with a previous study, (26% +/- 8%; less than 4% in normals (p less than 0.001) and antibody OKT10 reactive cells (39% +/- 20% versus 10% +/- 4%) (p less than 0.01), suggesting in vivo activation. However, their PBL did not react with antibody B3/25 (antitransferrin receptor), a marker found on normal PBL after in vitro activation by mitogens (BMT patients less than 5%; normal PBL T cells plus PHA 45% +/- 11%). These results demonstrate that BMT patients have: (A) an abnormal ratio of T-cell subsets in the presence or absence of clinically significant GVDH disease so that these measurements were not useful in monitoring patients; (B) an increased number of T cells with cell surface phenotype (OKT8+, Ia+, OKT10+, B3/25-) that is distinct from normals but similar to patients with infectious mononucleosis or acquired hypogammaglobulinemia. | |
| 7114076 | Immune complexes in primary biliary cirrhosis. Higher prevalence of circulating immune com | 1982 Aug | A longitudinal study, examining the levels of immune complexes serially for three years, in serum from 88 patients with primary biliary cirrhosis was performed by the Raji cell radioimmunoassay. Studies of the association of autoimmune features in primary biliary cirrhosis and the effect of D-penicillamine therapy in relation to the levels of complexes were carried out. Twenty-two patients (25 percent) were found to have autoimmune features, such as Sjögren's syndrome, rheumatoid-like arthritis, scleroderma, Raynaud's disease, and Hashimoto's thyroiditis. In this subset of patients with primary biliary cirrhosis, a significantly higher prevalence (86 percent) of circulating immune complexes was detected compared with those patients showing no autoimmune features (60 percent). In addition, patients with associated autoimmune features had higher mean levels of immune complexes (259.7 micrograms AHG eq/ml) compared with those without autoimmune features (202.1 micrograms AHG eq/ml). The mean levels of complement C4, reflecting activation of classic complement pathway, were significantly lower in patients with elevated immune complexes and associated autoimmune features. The mean level of immune complexes in 13 patients receiving D-penicillamine, in contrast to the placebo group, decreased at one year but subsequently was greater than the initial level. Patients who had normal levels of immune complexes and received penicillamine therapy continued to have complex levels within the normal range for up to three years of follow-up study, but patients receiving placebo showed significantly elevated levels at subsequent intervals. Thus, levels of immune complexes in primary biliary cirrhosis may reflect the association with autoimmune features. | |
| 3922321 | Small-cell lymphoma and Sjögren's syndrome. Lymphoplasmacytic subvariant of small-cell ly | 1985 May | To our knowledge, the association of the plasmacytoid variety of small-cell lymphoma with primary Sjögren's syndrome has not been reported. We describe a patient with SS who developed plasmacytoid small-cell lymphoma. As opposed to the commonly detected IgM, the lymphocyte surface immunoglobulins contained monoclonal IgA/kappa light chains. In addition to the unique immunopathologic features, the impressive response to chemotherapy and the importance of surface immunoglobulin markers in the diagnosis of malignancy in Sjögren's syndrome are discussed. | |
| 57714 | Malignant lymphomas of the salivary glands. Review of the literature and report of 33 new | 1976 Apr | Malignant lymphomas involving major salivary glands have been reported to occur in 31 cases. To these, we add 33 cases, 17 of which were studied in detail from the points of view of clinical presentation, classification (Rappaport), staging (Ann Arbor), therapy, and subsequent course. The parotid gland was involved much more frequently than the submandibular gland. No example of sublingual gland involvement was discovered in the present series. Most of the patients were in the sixth and seventh decades of life. Noteworthy is that all sub-types of lymphosarcoma were encountered, with only a single case of Hodgkin's disease present. In four of the patients, the characteristic histologic picture of lymphoepithelial lesion was found in juxtaposition to malignant lymphoma. The majority of patients received one or more courses of postoperative radiotherapy, which offered the best chance for long-term remission. However, only 40% of patients were free of disease after two years. | |
| 1096999 | Immunoglobulin metabolism in disease. | 1975 | Immunodeficiency and hypogammaglobulinemia are shown to occur by a variety of pathophysiologic mechanisms. Hypogammaglobulinemia may be caused by decreased synthesis of all classes of immunoglobulins, or may involve defective synthesis of selective classes of immunoglobulins. Alternatively, hypogammaglobulinemia may be due to a disorder of endogenous catabolic pathways of a single immunoglobulin class, or of all immunoglobulin classes. Finally, hypogammaglobulinemia may be caused by excessive loss of immunoglobulins into the urinary or gastrointestinal tracts. | |
| 390331 | The regulation of prostaglandin E1 formation: a candidate for one of the fundamental mecha | 1979 Aug | Vitamin C stimulates the formation of PGE1 in human platelets. The effect occurs over the physiologically relevant range of concentrations. PGE1 is required for T lymphocyte function and plays a major part in the regulation of immune responses. PGE1 is also important in the regulation of collagen and ground substance metabolism, in cholesterol metabolism and in regulation of responsiveness to insulin. It is proposed that defective formation of PGE1 could account for many of the features of scurvy and for many of the reported therapeutic effects of vitamin C. If correct, vitamin C will be of value only in conjunction with an adequate supply of dihomogammalinolenic acid, the precursor of PGE1. Essential fatty acids, pyridoxine and zinc are all required to achieve this. | |
| 6446896 | An overview of immunology with special reference to oral disease. | 1980 Apr | This overview of the current state of knowledge of the immune system as it is relevant to the oral cavity in health and disease, is presented to illustrate the significance of immunology to the practice of dentistry. Thus immunological mechanisms contribute in a major way to the pathogenesis of the two most common dental disorders and it may be that the ultimate control of dental caries may be through manipulation of the mucosal immune apparatus. Future advances require a clearer and more quantitative analysis of oral mucosal immunity in relation to health and disease. | |
| 6133362 | Histocompatibility (HLA) antigens and eye diseases other than uveitis. | 1983 Jan | In recent years, numerous studies on the possible associations of histocompatibility (HLA) antigens with various eye diseases other than uveitis have been carried out. This paper presents, discusses and evaluates the results of these studies. Undoubtedly, apart from acute anterior uveitis, HLA-typing has very limited usefulness in the practice of clinical ophthalmology. Many reported HLA associations with other eye diseases have not been confirmed by subsequent studies. However, a sizable residuum of highly significant and reproducible associations between HLA antigens and several eye diseases remains, suggesting that HLA-typing in patients with these diseases may contribute to the understanding of pathogenesis and etiology and may prove a valuable prognostic indicator for some diseases. | |
| 5015047 | Cell-mediated immune responses in chronic liver diseases. | 1972 Feb 26 | Studies of the cell-mediated response to liver antigens, using the leucocyte migration test, in 163 patients with various liver disorders showed that abnormal responses were almost confined to active chronic hepatitis (53% abnormal), primary biliary cirrhosis (64%), and cryptogenic cirrhosis (29%). The test was also abnormal in five out of seven patients with jaundice due to drug hypersensitivity and in one patient with acute infectious hepatitis at a time when mitochondrial antibodies were present in the serum. More of those with active chronic hepatitis on prednisone or azathioprine had normal tests than of those who were untreated, and in 8 out of 10 examined serially during therapy there was an accompanying improvement in leucocyte migration. Abnormal responses to salivary gland or kidney antigens were also found in nearly half of those with features of Sjögren's syndrome or renal tubular acidosis as part of a multisystem involvement-this, though occurring in cryptogenic cirrhosis, was found with greater frequency in active chronic hepatitis and primary biliary cirrhosis. These cell-mediated immune responses, perhaps triggered by the initial damage to the liver from viral or other agents, may be responsible both for the perpetuation of the liver disease and, because of common surface antigens, for the damage to other organs. | |
| 3358796 | The American Rheumatism Association 1987 revised criteria for the classification of rheuma | 1988 Mar | The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects. | |
| 2217956 | Rheumatoid arthritis. | 1990 Aug | RA is a common disease with a worldwide prevalence of about 1% with an annual incidence of about 3/10,000 adults. It is two to three times more common in women. There is some evidence that over the last few decades the disease is declining in incidence or severity. Patients with RA have a reduced life expectancy and a one in three chance of becoming disabled, depending on the severity of the disease at onset. The cause of the disease is unknown, although genetic factors account for up to 30% of disease susceptibility. The most important genetic factors are related to HLA-DR4 and DR1, which may have identical regions conferring the risk of disease. Many infectious agents have also been implicated in the etiology of RA, although there is no good epidemiologic evidence to support the laboratory findings. Hormonal and reproductive factors are known to play a major role in disease pathogenesis. Both pregnancy and the oral contraceptive pill are believed to be protective against development of the disease, although they may act by delaying or modifying the course of the disease rather than conferring "immunity". | |
| 3520431 | Rheumatoid arthritis of the hand. | 1986 Apr | Rheumatoid arthritis often begins in the hand, and upper extremity function can be seriously impaired with progression of the disease. When numerous areas are involved, a multitude of deformities can arise. Before initiating treatment of an arthritic patient, the surgeon must understand the natural course of the disease process, the response to medical treatment, and the functional limitations the disease has imposed. This article describes the examination for and treatment of this disease. | |
| 3318425 | Rheumatoid arthritis: clinical considerations in diagnosis and management. | 1987 Oct 30 | Advances in the understanding of the immune response, in immunogenetics, and in better identification of microbial agents that produce arthritis have made possible more accurate diagnosis of rheumatoid arthritis. Epidemiologic study of groups of rheumatoid patients and their response to therapy has provided a broader perspective of the disease's course and management. Therapy must be guided by the acute or chronic phase of the disease and must embrace chemical, psychologic, and physical modalities to achieve the goals of pain relief and the restoration of immune balance. Rheumatoid arthritis can no longer be considered benign since it impairs the duration as well as the quality of life. Therapy should be aggressive depending upon the predictors of more destructive disease. | |
| 3277684 | Mortality in rheumatoid arthritis. | 1988 | Rheumatoid arthritis (RA) is often regarded as a non-fatal disease. Yet patients with RA have a substantially reduced life expectancy. Increased mortality in RA is associated with a long disease duration, with severe disabling arthritis and with systemic involvement. Patients with chronic RA are particularly at risk of death from bacterial infection and renal disease. The influence of treatment on mortality remains unclear. In patients with mild RA, the treatments may be more toxic than the disease. | |
| 1948097 | Rheumatoid arthritis, food, and allergy. | 1991 Aug | One of the most promising lines of research on the etiology and pathogenesis of rheumatoid arthritis (RA) is its association with the genetically determined MHC class II antigens. The function of these macromolecules, presentation of antigens to the T-helper cells, supports the possibility that external antigens influence RA. We review available literature concerning the relationship between RA and food. Circumstantial evidence suggests that some foods or food components might influence subgroups of RA patients, although many of the publications on this subset do not meet acceptable standards of modern medical research. |