Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2844616 | Oxidants, inflammation, and anti-inflammatory drugs. | 1988 Oct | Species such as superoxide radical (O2-), hydrogen peroxide (H2O2), hydroxyl radical (.OH), and hypochlorous acid (HOCl) can be formed in vivo, e.g., by activated phagocytic cells. Generation of .OH from H2O2 in vivo usually involves iron-dependent reactions. Good evidence exists for increased generation of oxidants in vivo in patients with active rheumatoid disease, but the contribution of these oxidants to the disease process is still uncertain. The likelihood that anti-inflammatory drugs used in the treatment of arthritis could act by scavenging oxidants or preventing their formation is discussed. | |
| 3096341 | Human synovial fibroblasts produce urokinase-type plasminogen activator. | 1986 Nov | The plasminogen activator produced by cultured human synovial fibroblasts was investigated both biochemically and immunologically. Stimulated either by all-trans-retinoic acid or by monocyte-conditioned medium, these fibroblasts elaborated a plasminogen activator with electrophoretic mobility similar to that of urokinase (Mr = 52 kilodaltons), and which also had immunologic cross-reactivity with urokinase. The plasminogen activator found in rheumatoid synovial fluids has been shown to be of the urokinase type. The findings reported here are consistent with the notion that synovial fibroblasts are a source of this proteinase. | |
| 1908092 | Transforming growth factor beta stimulates urokinase-type plasminogen activator and DNA sy | 1991 Aug 15 | Transforming growth factor beta (TGF-beta) is usually associated with matrix formation and tissue repair; in contrast, cellular expression of the serine proteinase, urokinase-type plasminogen activator (u-PA) is often correlated with tissue remodeling, as well as with cell migration and transformation. We report here that purified recombinant human TGF-beta (greater than or equal to 300 pg/ml) can stimulate rapidly (within 2 h) the u-PA activity of nonrheumatoid synovial fibroblast-like cells. As for interleukin 1 (IL-1), u-PA mRNA levels are raised in response to TGF-beta, but unlike IL-1, no increase in prostaglandin E2 levels occurs. In contrast to a number of other examples in the literature, in which these two cytokines have opposing actions, TGF-beta can potentiate the action of optimal concentrations of IL-1 in enhancing u-PA expression. These effects of TGF-beta are similar to those of all-trans-retinoic acid. In addition, synovial fibroblast DNA synthesis was stimulated by TGF-beta. Because TGF-beta has been detected in the synovia of patients with rheumatoid arthritis and has been shown to reduce the collagenase levels and proliferation of synovial fibroblast-like cells, it has been proposed by others to be involved beneficially in the reparative processes occurring in arthritic lesions. However, on the basis of our findings, we propose alternative functions for this cytokine--namely, roles in the destructive events as well as in the synovial hyperplasia observed in rheumatoid joints. | |
| 2204556 | [Analysis of islet cell surface antigen reactions with islet cell surface antibodies (ICSA | 1990 Jul 20 | Islet cell surface antibodies (ICSA) have been detected in the sera of many patients with insulin-dependent diabetes mellitus (IDDM). They have also been demonstrated to affect the plasma membranes of beta-cells in vitro. To determine the pathogenetic role of ICSA in IDDM, we studied their prevalence and their relationship to lymphoblastogenesis (LBG) in diabetes as well as in other autoimmune diseases. Furthermore, islet cell antigens (IAg) were characterized from rat pancreatic islet cells, using an affinity column consisting of human IgGs including ICSA. ICSA titers were measured by indirect immunofluorescence. Sera were determined as ICSA-positive when they reacted to more than 10% of 50-100 cells. The LBG investigation was carried out after a 4-day incubation with phytohemagglutinin (PHA), pokeweed mitogen (PWM), or concanavalin A (Con A). The LBG induced by IAg was investigated after an 8-day incubation. Lymphocytes included 75% CD3-positive cells and 5% CD20-positive cells. IAg were purified from ICSA-positive IgG coupled to CNBr-activated sepharose 4B. The prevalence of ICSA was 39% in patients with IDDM (11/28), 15% in non-insulin dependent diabetes mellitus (NIDDM) (16/109), 14% in Graves' disease (3/22), 29% in Hashimoto's disease (5/17), 12% in rheumatoid arthritis (3/25), 20% in systemic lupus erythematosus (SLE) (7/35), and 33% in Sjögren's syndrome (2/6). No ICSA were detected in 27 normal subjects. Although sera from the patients with autoimmune diseases contained antinuclear antibodies, antithyroid antibodies and/or rheumatoid factor, there was no relationship between the prevalence of such antibodies in patients with ICSA and those without it. In 3 patients (60%) with ICSA-positive IDDM, the lymphoblastogenic responses to PHA and PWM were decreased. A similar decrease was observed when comparing ICSA-positive NIDDM to ICSA-negative NIDDM (PHA: p less than 0.05; PWM: p less than 0.01). However, there was no relationship between HbA1 and the LBG response or between HbA1 and the presence of ICSA. The relative molecular weights (Mr.) of the IAg reacting with ICSA-positive IgG were around 67, 64, 55, and 20K in all but three patients with diabetes mellitus. IAg with a Mr. around 30K or less than 14K were also demonstrated in some patients with diabetes mellitus. The Mr. of IAg was the same in three patients with autoimmune disease as in diabetes mellitus, but it differed in three other similar patients.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 2068116 | Bone and the immune system. | 1991 Jul | There are several lines of evidence which provide support for an important relationship between immune cells and bone. Clinical studies of immunodeficiency syndromes have shown that abnormalities in bone shape are evident on x-rays, and peculiarities in the structure of the growth plate have been identified by histopathology. Studies of bone histology, and quantitation of cellular abnormalities, are scarce. Abnormalities in bone turnover, have, however, been identified in the nude mouse model. Many lines of evidence derived from in vitro bone studies have shown that lymphokines and monokines can influence bone formation and bone resorption. Some clinical studies of postmenopausal osteoporosis have indicated the possible presence of immune cell changes in this condition. Although several hypotheses have been formed regarding the exact mechanisms of the effect of immune cytokine on bone, this is clearly a very large area of study and there is a need for additional carefully controlled experiments with special emphasis on bone cells and bone matrix, especially in the human. As knowledge progresses regarding immunology and hematology, a clearer understanding of the lineages of the osteoblast and osteoclast will emerge and we will better understand how specialized bone cells interact with and react to their immune cell neighbors in the bone marrow and to immune system signals. These findings will have especially important implications for the local bone loss seen in rheumatoid arthritis, periodontal disease, and chronic osteomyelitis. | |
| 1886302 | [Two cases of interstitial pneumonitis with marked increase of tumor-associated carbohydra | 1991 May | Tumor-associated carbohydrate antigens, CA19-9 and SLEX have been used clinically as markers for malignancy. However, it is also known that these antigens are frequently elevated in the serum of patients with benign lung diseases. We have experienced two cases of interstitial pneumonitis with marked increase of carbohydrate antigens in serum, the level of which changed according to their clinical course. Case 1. A 64-year-old woman was admitted because of a cough and exertional dyspnea. Despite treatment with various antibiotics and prednisolone, she died of respiratory failure approximately two months after admission. Her CA19-9 and SLEX in serum elevated from 500 U/ml to 5506 U/ml and 167 U/ml to 1187 U/ml respectively in accordance with clinical deterioration. Autopsy revealed no malignancy. Case 2. A 57-year-old woman, who had been suffering from interstitial pneumonitis associated with rheumatoid arthritis, was admitted with a cough and fever. She responded to prednisolone therapy, however two years later she readmitted because of exacerbation and died of respiratory failure. The initial CA19-9 level in serum was 876 U/ml and dropped to 42 U/ml with prednisolone therapy. The serum antigen level again increased during the period of exacerbation, and showed 133 U/ml immediately before death. An immunohistochemical study of CA19-9 and SLEX in various tissues obtained by autopsy was performed in case 1. The distribution of these antigens in tissue was similar to that of normal individuals. The exceptions were the expression of these antigens on epithelial cells of microscopic honeycombing and on mucinous exudates in air spaces. | |
| 1668288 | T cell subset composition in remission phase of systemic connective tissue diseases. | 1991 May | The proportions and numbers of peripheral blood mononuclear cells bearing T-cell markers (CD3/HLA-DR, CD4/CD29, CD4/CD45, CD8/CD56) were analyzed using two-color flow cytometric analysis in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS) in the remission phase of the diseases. The number of T cells (CD3+) in the blood was significantly decreased in SLE patients only; in these patients, but also in RA patients, an increased number of activated T cells (CD3+ HLA-DR+) was found. The number and proportion of helper T cells (CD4+) were decreased in SLE and SS, and normal in RA patients. In contrast, helper-inducer (CD4+ CD29+) and suppression-inducer (CD4+ CD45+) cells were both significantly increased in RA patients, decreased in SLE (only CD4+ CD45+ significantly) and unchanged in SS patients. Interestingly, however, the proportions of helper-inducer cells relative to total helper (CD4+) cell pool were significantly increased in all three groups of patients, whereas the proportion of suppression-inducer (CD4+ CD45+) cells was significantly decreased, but in SLE patients only. It is thus possible that this parameter is most pertinent to the disease status in the model studied. The population of CD8+ cells appeared more abundant in SLE patients, and the pool of CD8+ CD56+ cell was significantly enlarged in RA patients. It appears that the remission phase of disease in RA, SLE and SS patients still contains a substantial activation of the immune system, but the respective mechanisms are quite different in RA patients on one side, and SLE and SS patients on the other side.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2091202 | [Oral contraception]. | 1990 Nov | ||
| 2141847 | Decreased suppressor-inducer T lymphocytes in multiple sclerosis and other neurological di | 1990 Jul | Decreased numbers of CD4+CD45R+ suppressor-inducer T cells have been reported in patients with a variety of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis but not in patients with other neurological diseases. We now report our findings using murine monoclonal antibodies and two-color flow cytometric analysis on CD4+CD45R+ T cells in 22 patients with chronic progressive multiple sclerosis, 23 patients with other neurological diseases and 42 normal, healthy controls. Suppressor-inducer T cells were significantly reduced (p less than 0.001) in both patients with multiple sclerosis and other neurological diseases as compared to controls. Both patient populations had elevated helper T cell subset ratios. Thus, our data suggests that decreases in suppressor-inducer T cells may represent a common immunological defect among autoimmune and presumably non-autoimmune neurological disorders. | |
| 1706817 | [FK-506. A new immunosuppressive drug]. | 1990 Jul | In this brief review, we outline the properties of the new macrolide immunosuppressant FK-506. This selective anti-T cell agent has a similar mode of action to cyclospirin A (CSA). It is, however, more powerful, has the capacity (unlike CSA) to reverse liver allograft rejection and appears to have a higher therapeutic index than CSA in patients receiving organ transplants. Preliminary data suggest that renal function is better in recipients of liver transplants given FK-506 as primary therapy compared with those given CSA. In addition, evidence has been presented that FK-506-treated patients have shorter hospital stay than those receiving treatment with CSA. Other factors require to be taken into account, but it may be that it will prove less expensive in the future to treat patients with FK-506 than with CSA. The potential of FK-506 for the control of autoimmune diseases has been demonstrated in rodent models of rheumatoid arthritis, type I diabetes, posterior uveitis, allergic encephalomyelitis and glomerulonephritis. In the clinical field, FK-506 has been used in two cases of nephrotic syndrome resulting from glomerulonephritis; there was improvement in proteinuria and no decline in renal function. Studies to date have been restricted to one clinical centre although many hundreds of organ graft recipients have been studied. Both longer term and multi-centre investigations are urgently required, but it appears that FK-506 may offer considerable potential as an immunotherapeutic agent. | |
| 2105008 | Mediastinal lymph node enlargement on CT scans in patients with usual interstitial pneumon | 1990 Feb | Usual interstitial pneumonitis (UIP) is a chronic pulmonary process with a characteristic peripheral fibrotic pattern on gross pathologic lung sections and CT scans. This condition is often idiopathic, but asbestosis, rheumatoid arthritis, and scleroderma may cause the same peripheral fibrosis in the lungs. UIP is associated with an increased incidence of pulmonary neoplasms. The purpose of this study was to evaluate the size of mediastinal lymph nodes in patients with UIP in whom no evidence was seen of malignancy or current active infection. CT scans of 14 patients (12 with idiopathic pulmonary fibrosis and two with collagen vascular disorders) were assessed for lymph node location (American Thoracic Society mediastinal map) and size. In 13 of 14 patients, nodes measured greater than threshold size values. Nodes as large as 20 x 30 mm were identified in three patients. Nodal sites 10R, 4R, 2R, 5, and 6 were most commonly abnormal. We conclude that increase in the size of mediastinal lymph nodes as shown on chest CT scans is common in patients with UIP, occurs without superimposed infectious or malignant complications, and is thus presumably part of the chronic inflammatory process. Consequently, lymphadenopathy in these patients does not suggest that they have lung cancer also. | |
| 2527098 | Detection of autoantibodies in a quantitative immunoassay using recombinant ribonucleoprot | 1989 May | A human cDNA expression library was screened with anti-ribonucleoprotein (RNP) antibodies from patients with connective tissue diseases. Three cDNA clones were isolated encoding 70 kD, A and B" ribonucleoprotein autoantigens which were expressed as beta-galactosidase fusion proteins. Antigens were purified and used to develop sensitive ELISAs suitable for the routine screening of large series of sera from patients with connective tissue diseases. More than 400 sera were tested both by ELISA and by immunoblotting. The ELISA was found to be at least as sensitive as immunoblotting and very specific. Anti-70 kD antibodies were found in 94% of patients with mixed connective tissue disease (MCTD), in 4% of patients with other connective tissue diseases but not in normal controls. Furthermore, the use of recombinant 70 kD antigen enabled us to discriminate between anti-70 kD antibodies present in anti-Sm and in anti-(U1) RNP sera. Recombinant A antigen contained at least two autoantibody-reactive sites; one unique for the A protein and another cross-reactive with anti-B" antibodies. Antibodies reactive with the unique site were found in 83% of MCTD patients, in 4% of patients with other connective tissue diseases and not in normal controls. Antibodies against the cross-reactive B" epitope present on A and B" recombinant antigens, were found in high titres in a small percentage of patients with systemic lupus erythematosus (SLE, 5%) and rheumatoid arthritis (RA, 2%). | |
| 2814209 | C3-containing serum immune complexes in patients with systemic lupus erythematosus: correl | 1989 | Although testing for circulating immune complexes (CIC) is regarded as a useful, complementary, laboratory parameter in the differential diagnosis and management of immune complex-induced vasculitis syndromes, there is still an uncertainty with regard to assay systems used for the demonstrated of soluble immune complexes. This is partly due to difficulties in the reproducibility, handling and principle limitations of available test systems for the assessment of soluble immune complexes in body fluids. In the present communication a modification of the anti-C3 test for the determination of CIC was developed using nitrocellulose as a solid phase matrix. IgG-, IgA- and IgM-containing CIC were determined and quantified using standard immune complex preparations. When 39 sera of SLE patients, 12 sera of patients with vasculitis syndromes, 10 sera of rheumatoid arthritis patients and 11 sera of patients with ankylosing spondylitis were tested, predominantly IgG-containing CIC could be demonstrated. Only in SLE patients was a significant amount of other immunoglobulin isotypes detected in CIC. In these patients a significant difference of IgG-containing CIC levels was found with regard to patients with high and low disease activity (P less than 0.0001). A significant correlation was also established between IgG-containing CIC and anti-dsDNA antibodies (P less than 0.001). In a longitudinal study the isotypes in the isolated CIC were found to be constant. | |
| 2650989 | The pathobiology of the terminal complement complexes. | 1989 | C5b and the other late-acting complement components can assemble the two terminal complexes (TCC) C5b-9 and SC5b-9. In addition to the lytic effects of C5b-9 it has been demonstrated that sublytic amounts of C5b-8 or C5b-9 can stimulate several important cellular activities. These effects may be important to explain the role of C5b-9 in the production and progression of several pathological conditions that has been demonstrated in experimental models of disease. With the help of antibodies that specifically recognize C9 neoantigens, deposits of TCC have been identified in human tissues, not only in immunological diseases but also in certain nonimmunological diseases. In the latter it has been shown that often there is no concordance between deposits of TCC and those of immunoglobulins and C3. Methods for measuring SC5b-9 in biological fluids have also been developed. Normal plasma was found to have low levels of SC5b-9. Increased plasma levels of SC5b-9 have been observed during the active phase of SLE nephritis, in certain infections and during cardiopulmonary bypass. Increased levels were also found in the cerebrospinal fluid of patients with inflammatory diseases of the central nervous system and in the synovial fluid of patients with rheumatoid arthritis. Autoantibodies to C9 neoantigens in plasma of certain patients with autoimmune, infectious or neoplastic diseases have recently been recognized. Additional work is needed to better delineate the potential usefulness of these findings for diagnosis and evaluation of disease activity. | |
| 2531473 | [The results of 5 years' use of a method for heparin cryoprecipitation of plasma proteins | 1989 | The paper treats the results of the 5-year use of plasma protein heparin cryoprecipitation (selective plasmapheresis) (SPA) in patients with immune complex pathology. The method consists in the removal of fibronectin and bound complement components, cryoglobulins, cryofibrinogen, circulating immune complexes (CIC), and other gross-dispersed proteins in the presence of heparin in the cold. The SPA was applied to 122 patients with immune complex diseases and syndromes. Altogether 1279 procedures were carried out. The method turned out effective in 80% of patients with hemorrhagic vasculitis, systemic lupus erythematosus, rheumatoid arthritis, and other types of vasculitis. The changes in the blood serum concentration of immune complexes correlated with the time-course of changes in the clinical and laboratory parameters. The SPA efficacy was in agreement with the reduction in the level of immune complexes. Provided 2-3 procedures were carried out a week, the lowering of the level of immune complexes and other laboratory parameters marking the degree of inflammation could be seen by procedures 4-6. Therefore, to attain a stable clinical effect, its is necessary to perform not less than 6 SPA procedures. It has been demonstrated that SPA can be used an unlimited number of times, for the use of the method does not entail the development of plasma protein deficiency. This circumstance is of paramount importance for the treatment of chronic relapsing immune complex diseases. | |
| 3357087 | Analysis of experimental immune synovitis cartilage using monoclonal antibodies reactive t | 1988 | This study details the macromolecular changes in cartilage involving proteoglycan molecules in an animal model of rheumatoid arthritis. In experimental chronic immune synovitis, fluorescein-conjugated mouse IgG and three monoclonal antibodies (MAbs 2G2, 2E9, and 6C9) portraying differing fine antigenic specificity for rabbit cartilage proteoglycan monomer were utilized to detail alterations in cartilage proteoglycan. In normal and IgG-immune animals, fluorescein isothiocynate (FITC)-conjugated MAbs 2G2 and 2E9 stained cellular/pericellular (C/PC) region intensely. FITC-MAb 2G2 stained cartilage interterritorial matrix as well. FITC-MAb 6C9 stained only C/PC area lightly but did not stain matrix. A marked decrease in staining intensity with FITC-MAb 2G2 was noted in cartilage sections derived from animals with immune synovitis. A corresponding increase in staining of cartilage was noted with FITC-MAb 6C9. The augmented staining of articular cartilage with FITC-MAb 6C9 was most prominent in femoral condyle tissue sections, which corresponded to the cartilaginous area, with the greatest severity in gross pathology. There was a slight augmentation of staining with FITC-MAb 2E9, especially in the C/PC area of medial/femoral cartilage. In addition, the animals with immune synovitis showed abortive cartilage repair exemplified by the presence of chondrocyte cloning (up to 20 cells) which correlated with increased FITC-MAb 2G2 staining. The differential MAb staining patterns of cartilaginous tissues obtained utilizing FITC-conjugated monoclonal antibodies with known fine antigenic specificity indicates a modulation of proteoglycans involving predominantly core protein epitopes in the articular cartilage of animals with chronic immune synovitis. | |
| 3098653 | [Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory d | 1986 Sep | Damaging effects on the gastrointestinal tract of proglumetacin maleate (PGM), a new indomethacin (IND) derivative, were examined in comparison with those of IND. Gastric and small intestinal lesions were maximum 4 and 24 hr after a single oral administration of PGM, respectively. Ulcerogenic effects of PGM on the gastric mucosa were approximately 1/7 and 1/10 times as potent as those of IND on a molar ratio 4 hr after single oral dosing to fasting and feeding rats, respectively. PGM was also less active on the small intestinal mucosa 24 hr after single oral dosing. After repeated dosing for 7 days, ulcerogenic effects of PGM were about 1/3 and 1/2 times more potent than those of IND on the gastric and the small intestinal mucosa, respectively. The weak ulcerogenicity of PGM appears to be due to the fact that it has little direct action on the gastrointestinal mucosa. On the other hand, protective effects of PGM on diarrhea induced by arachidonic acid in mice were about 1/2 times as potent as those of IND in both 1 and 4 hr pretreatments. So PGM must have less inhibitory effects on prostaglandin biosynthesis in the intestine than IND. PGM is a safer drug than IND because it has less damaging effect on the gastrointestinal mucosa. Therefore, it may be much more useful for the treatment of chronic inflammatory disorders like rheumatoid arthritis. | |
| 3766715 | Frequencies of complex diseases in hybrid populations. | 1986 Aug | Diseases of complex etiology demonstrate considerable variation in their frequencies in different ethnic populations. Noninsulin-dependent diabetes mellitus (NIDDM), rheumatoid arthritis, and several cardiovascular diseases constitute examples of such disorders. In genetic studies involving hybrid populations of known ancestry, it is of interest to compare and correlate disease prevalence with the admixture proportion, the latter estimated from a number of polymorphic genetic markers. Theoretical formulations are provided relating disease prevalence in a hybrid population to the admixture proportion under different models of disease transmission. It is shown that the relationship between admixture proportion and disease frequency provides discriminatory power regarding the mode of inheritance. This method is illustrated with an example comparing the proportion of Amerindian ancestry in Mexican-Americans and the prevalence of NIDDM. It is found that genetic factors are involved in susceptibility to NIDDM, but the mode of inheritance cannot be explained by any simple genetic model, and the role of sporadic events cannot be totally ruled out. | |
| 3963625 | Subclinical pulmonary involvement in collagen-vascular diseases assessed by bronchoalveola | 1986 Apr | Collagen-vascular disorders (CVD) are commonly associated with chronic interstitial lung disease. Clinicopathologic observations suggest that inflammatory process of the lower respiratory tract may appear prior to fibrosis. Subclinical pulmonary involvement, as assessed by bronchoalveolar lavage (BAL) was evaluated in 61 patients with various CVD but free of clinical pulmonary symptoms and with normal chest roentgenograms. Eight of 61 had abnormal pulmonary function tests (PFT) at entry to the study. Total BAL cell yield from nonsmokers was greater in patients with abnormal than in those with normal PFT (p less than 0.05). Abnormal differential count of BAL cells was noted in 29 of 61 patients (48%). Lymphocyte alveolitis (lymphocytes greater than or equal to 18%) was a characteristic finding in patients with primary Sjögren's syndrome (11 of 25) or Sjögren's syndrome associated with another CVD (4 of 8). Neutrophil alveolitis (neutrophils greater than 4%) with or without increased percentage of lymphocytes occurred in patients with CVD classically associated with pulmonary fibrosis: progressive systemic sclerosis (6 of 10), rheumatoid arthritis (1 of 4), dermatopolymyositis (2 of 3), and mixed connective tissue disease (3 of 8). An increased percentage of eosinophils was detected in 1 patient with progressive systemic sclerosis. Bronchoalveolar lavage abnormalities were more frequently detected in patients with active and severe extrapulmonary disease. On follow-up PFT 12 months later, 11 patients with normal BAL and 10 patients with lymphocyte alveolitis had not deteriorated. In marked contrast, the presence of neutrophils in BAL was associated with a progressive deterioration of PFT in 6 of 7 untreated patients, whereas 4 corticosteroid-treated patients with neutrophil alveolitis had not deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1778220 | Expression of transferrin receptors by monocytes and peritoneal macrophages from renal fai | 1991 Dec | Approximately 20% of monocytes and peritoneal macrophages from renal failure patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were transferrin-receptor (TfR) positive by immunofluorescence, whereas cells from normal controls were generally TfR negative, as were monocytes from rheumatoid arthritis patients and from renal failure patients treated by haemodialysis. There was a significant correlation between the length of time on CAPD and the proportion of TfR-positive blood monocytes. CAPD peritoneal macrophages possessed 6.7-37.1 x 10(3) transferrin binding sites per cell, with a Ka of 3-25 x 10(7) mol l-1. In culture, monocytes from CAPD patients showed a progressive decrease in TfR expression, while in contrast about 20% of monocytes from normal controls which were originally 100% TfR negative expressed TfR after 3 days in culture. These findings indicate that regulation of TfR in monocytes/macrophages is complex, and that frequent removal of peritoneal cells during dialysate exchange may place a strain on the bone marrow, resulting in the release of an increasingly immature population of TfR positive monocytes to the circulation in CAPD patients. |