Acute phase response in rheumatoid arthritis patients treated with low doses of cyclosporin A.
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Acute-Phase Proteins↗
Biomedical subjects
S H Mackiewicz
Publications and source records attributed to S H Mackiewicz.
Comparison of microheterogeneity of alpha-1-acid-glycoprotein in serum and synovial fluid from rheumatoid arthritis patients.
Microheterogeneity of alpha-1-acid glycoprotein was studied using affinity immunoelectrophoresis with concanavalin A as a ligand in the samples of serum and synovial fluid obtained at the same time from 22 patients with rheumatoid arthritis. Individuals with intercurrent infection or other illnesses were excluded from the study. The results were expressed as reactivity coefficient (RC). Disease activity was evaluated by Mallya-Mace Activity Score, Lansbury Joint Index and laboratory tests. In most of the studied samples the glycosylation pattern was similar, composed of a nonreactive variant and 2 reactive (the first and the second) with Con A variants. In seven samples of synovial fluid an extra third peak representative of the strongly reactive one with Con A fraction was observed. It was the cause of the remarkable elevation of AGP-RC. Moreover, the level of IgM and IgA RF was higher in the synovial fluid derived from these patients--with the presence of the third peak in AFF-EP with Con A--than in those without the considered fraction.
Adult↗
Lymphocyte phenotype studies of rheumatoid arthritis patients treated with methotrexate.
Seventy nine patients with rheumatoid arthritis (RA) were monitored for 12 months. Forty eight individuals were treated weekly with a low dose of methotrexate (MTX), and 31 received nonsteroid antiinflammatory drugs (NSAID) only. The mean total dose of MTX was 413 mg with a range from 250 to 735 mg. The phenotype of lymphocytes was analyzed using double immunofluorescence and a panel of monoclonal antibodies. The clinical status of 33 MTX-treated patients improved, in 9 neither clinical nor laboratory improvement was noticed. Six patients were withdrawn from the study because of adverse reactions. We observed no changes in the percentage of CD3, CD4, CD8 and CD25 positive lymphocytes in both MTX and NSAID-treated groups. However, the percentage of CD19 positive cells significantly decreased during 12 month observation (15.1 +/- 6.5% v.s. 10.2 +/- 5.0, p < 0.01) in MTX-treated subjects. Moreover, this percentage increased (9.4 +/- 6.7% v.s. 17.1 +/- 1.1%, p < 0.01) in NSAID-treated patients.
Adult↗
Contrasting effect of oral and intravenous cyclophosphamide treatment on phenotypes of human peripheral blood lymphocytes.
Twenty three rheumatoid arthritis (RA) patients treated with cyclophosphamide (CTX) were observed for 6 months. Eight patients received CTX in a single intravenous dose (group I) and 15 orally in a single daily dose (group II). The surface antigens of lymphocytes, isolated from peripheral blood, were determined using immunofluorescence method. The clinical improvement was observed both in group I and in group II of patients. However, in patients receiving CTX intravenously amelioration of the disease appeared quicker. The percentage of CD3+ and CD8+ T cells remained unchanged. In group I we observed decrease in the number of CD4+ T cells (60.1 +/- 11.5% and 43.8 +/- 12.5%, before and after treatment respectively, p < 0.01), in group II this level remained unchanged. In both groups the percentage of CD19+ B cells decreased (14.7 +/- 9.2% and 8.0 +/- 6.1%, before and after treatment respectively in group I, p < 0.01; 17.4 +/- 12.3% and 11.0 +/- 7.1%, before and after treatment respectively in group II, p < 0.01). Moreover, the percentage of activated T cells (CD25+ cells and HLA-DR+ cells) was reduced in both groups.
Administration, Oral↗
Different capabilities of monocytes from patients with systemic lupus erythematosus and rheumatoid arthritis to induce glycosylation alterations of acute phase proteins in vitro.
The effect of conditioned medium on the biosynthesis and glycosylation profile of acute phase proteins secreted by the human hepatoma cell line Hep G2 was studied. Conditioned medium was prepared from nonactivated [CM-LPS(-)] and ex vivo lipopolysaccharide activated [CM-LPS(+)] monocytes from eight patients with active rheumatoid arthritis (RA), five patients with active systemic lupus erythematosus (SLE), and seven healthy subjects. The biosynthesis of albumin, alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor and the profile of glycosylation of proteinase inhibitor were analysed. CM-LPS(-) from patients with SLE had a similar effect to CM-LPS(-) from healthy subjects. In contrast, CM-LPS(-) from patients with RA had the same effect as CM-LPS(+) from healthy donors. A similar effect to that of CM-LPS(+) of healthy subjects was seen with CM-LPS(+) from patients with SLE and with CM-LPS(+) from patients with RA. The treatment of CM-LPS(+) with antibodies against interleukin 6 neutralised most of its ability to induce changes in the biosynthesis and glycosylation of acute phase proteins. Antibodies to interleukin 1 and tumour necrosis factor alpha had only a limited effect on the ability of CM-LPS(+) to induce changes of albumin and alpha 1-antichymotrypsin syntheses, whereas they had no effect on the biosynthesis and glycosylation of proteinase inhibitor. These results indicate that: (a) monocytes isolated from patients with active SLE and active RA have different capabilities of inducing alterations of acute phase proteins in vitro; (b) ex vivo activation of monocytes from patients with SLE leads to the full induction of its capabilities to change acute phase proteins, whereas the activation of monocytes from patients with RA has no additive effects; and (c) interleukin 6 seems to be a major cytokine involved in the regulation of the glycosylation pattern of acute phase proteins.
Acute-Phase Proteins↗
[Alpha-1-acid glycoprotein in differential diagnosis of rheumatic diseases].
In recent years, the investigation of acute-phase proteins with the aid of affinity electrophoresis employing lectins as carrier substance, has become ever more important, in particular in the diagnosis of inflammatory rheumatic diseases. In order to investigate the usefulness of a determination of alpha-1 glycoprotein microheterogeneity in the sera as a diagnostic parameter, we evaluated, on a prospective basis, the sera of 85 consecutive patients presenting at our department with various inflammatory rheumatic diseases (chronic rheumatoid arthritis [RA] [n = 22], seronegative spondarthropathies [SpA] [n = 15], polymyalgia rheumatica [PMR] [n = 10], polymyositis dermatomyositis [PM/DM] [n = 8], osteoarthritis [n = 18], and infectious diseases [n = 12]). The results were expressed as reactivity coefficient of the alpha-1 acid glycoproteins (AGP/RC). A significant increase in the AGP/RC was observed in patients with various infections, and in those with RA or SpA with intercurrent infection, as compared with patients with RA or SpA with no intercurrent infection, or in healthy controls. It also proved possible to differentiate between PM/DM and PMR. Determination of the erythrocyte sedimentation rate, and quantification of the C-reactive protein and of alpha-1 glycoprotein, permitted no discrimination between an increase in inflammatory activity related to the basic disease, and an intercurrent bacterial infection. The results show that the determination of qualitative changes in the acute phase proteins, in particular alpha-1 acid glycoproteins, may make it possible to differentiate between inflammatory and infectious diseases. This examination technique may be of future clinical importance.
Adult↗
Mechanisms regulating glycosylation of human acute phase proteins.
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Acute-Phase Proteins↗
Binding of C-reactive protein (CRP) by human peripheral blood lymphocytes in vivo.
Antigenicity of C-reactive protein (CRP) on the surface of human lymphocytes was investigated by use of indirect immunofluorescence technique with anti-CRP antibodies. CRP on the lymphocyte surface (sd-CRP) belongs to two different categories: i) CRP produced by lymphocytes and inserted into cell membrane (s-CRP), ii) CRP produced primarily by the liver and bound by the lymphocytes (sb-CRP) in calcium-dependent manner. In human peripheral blood of healthy donors approximately 2.5% of lymphocytes expressed membrane CRP (s-CRP) and 1.5% of lymphocytes bound CRP in calcium-dependent manner (sb-CRP). Percentage of s-CRP lymphocytes increased in patients with rheumatoid arthritis, while population of sb-CRP lymphocytes did not change significantly, except cases where serum CRP concentration reached more than 50 micrograms/ml. Thus, it can be concluded that CRP is bound to the distinct population of lymphocytes, bearing specific membrane receptors.
Antigens, Surface↗
Microheterogeneity of acute phase proteins in the differentiation of polymyalgia rheumatica from polymyositis.
We studied an alpha-1-acid glycoprotein (AGP) and an alpha-1-antichymotrypsin (ACHT) microheterogeneity in sera of patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA/PMR), polymyositis/dermatomyositis (PM/DM) and healthy individuals by affinity electrophoresis with concanavalin A (Con-A) as the ligand. Our results are expressed as reactivity coefficients. The mean of AGP reactivity coefficients (AG-RC +/- SD) in PMR (0.92 +/- 0.17) and GCA/PMR (0.91 +/- 0.12) were significantly lower compared with the mean AG-RC in patients with PM/DM (1.48 +/- 0.52) as well as in healthy individuals (1.34 +/- 0.9). Moreover, an additional microheterogeneous form of AGP was noted in patients with PM/DM. In parallel, we also found that the mean of ACHT reactivity coefficients (AC-RC +/- SD) were lower in patients with PMR (2.94 +/- 1.24) and GCA/PMR (1.66 +/- 0.16) compared with healthy individuals (3.92 +/- 1.17). The mean of AC-RC in patients with PM/DM (6.74 +/- 4.35) was significantly higher than in patients with PMR and GCA/PMR as well as in healthy individuals. Our results show that the changes in reactivity of AGP and ACHT with Con-A are useful diagnostic markers for the differentiation of PMR and GCA/PMR from PM/DM.
Acute-Phase Proteins↗
Microheterogeneity of alpha 1-acid glycoprotein in the detection of intercurrent infection in patients with rheumatoid arthritis.
We evaluated the clinical usefulness of determinations of alpha 1-acid glycoprotein (AGP) microheterogeneity in distinguishing patients who have active rheumatoid arthritis (RA) from those who have RA and an intercurrent infection. AGP microheterogeneity was studied by affinity electrophoresis with concanavalin A as the ligand, and the results were expressed as reactivity coefficients (RC). Significant differences were found between the mean RC (+/- SD) in healthy individuals (1.27 +/- 0.16) and the mean RC in RA patients with intercurrent infection (1.74 +/- 0.90), as well as with the mean RC in RA patients with grades III and IV disease activity (0.92 +/- 0.18 and 0.81 +/- 0.25, respectively). Moreover, an additional microheterogeneous form of AGP, similar to that observed in non-RA patients with infections, was noted in RA patients with infections (sensitivity 100%, specificity 100%). The results show that an increase in AGP reactivity with concanavalin A is a sensitive indicator of intercurrent infection in patients with RA.
Arthritis, Rheumatoid↗
Quantitative changes in peripheral blood lymphocytes in erosive rheumatoid arthritis patients treated with methotrexate. Correlation with disease activity.
In order to better understand the immunological mechanisms involved in the pathogenesis of rheumatoid arthritis (RA), the level of various lymphocyte subsets in the peripheral blood of 29 patients with erosive RA was determined. All the patients were treated with methotrexate for 2 years. The total number and the proportion of CD3 cells, CD3+CD4+ and CD3+CD8+ cells did not change during the study. The initially increased level of CD19+ B-cells and CD19+CD5+ cells decreased during the treatment. The percentage of CD3-CD16+ natural killer cells was not affected by the treatment. At the inception of the study, we observed a deficiency of CD4+ CD45RA+ cells and the level of CD3+CD29+ cells was slightly increased. During the treatment we noticed significant elevation of CD45RA cells. Consequently, the CD29/CD45RA ratio significantly decreased. We showed significant correlation between changes in disease activity and changes in the level of CD19+ cells and CD4+CD29+ cells. Our results suggest that low-dose methotrexate may affect immunocompetent cells. The lowering in the CD29+ subset population associated with depletion of CD19 B-cells after methotrexate therapy may limit abnormal CD4+ cell activation and reduce the migration of lymphocytes into inflamed synovium.
Adult↗
Does C-reactive protein modulate T-lymphocyte function in methotrexate-treated rheumatoid arthritis patients?
Thirty-four patients with rheumatoid arthritis were treated with oral methotrexate for 6 months. Methotrexate was given as a single weekly dose of 7.5-10 mg. A correlation between serum concentration of CRP and proportion of CD8+ lymphocytes in peripheral blood was found in this group of patients. This correlation can be described by a linear regression equation. According to the results obtained, CRP suppresses lymphocyte function in patients with RA. This is the consequence of the stimulating effect on suppressor mechanisms.
Arthritis, Rheumatoid↗
Association of rheumatoid arthritis with Kartagener's syndrome in a patient with HLA-DR1-DR4-B27 haplotype.
A case of severe seropositive rheumatoid arthritis associated with Kartagener's syndrome in a patient positive for B27, DR4, and DR1 has been presented. A number of immunological disturbances were observed, especially defective granulocyte function and depressed delayed hypersensitivity.
Arthritis, Rheumatoid↗
Toxoplasmosis and systemic lupus erythematosus. Comparative serological studies.
There are still controversial views as to the relation between SLE and toxoplasmosis. Therefore, we looked for serological markers in both diseases. In patients with SLE (17), toxoplasmosis (28), and in normal controls (28) anti-Toxoplasma gondii antibodies, anti-nuclear antibodies of different specificities, anti-histone and anti-cardiolipine antibodies, as well as antibodies against most common public idiotypes were measured. Significant increases in antinuclear antibodies and other SLE-related antigens were observed in patients with SLE. On the contrary, low levels of these antibodies were found in toxoplasmosis patients and in controls. The same was true for 16/6 anti-DNA idiotype antibodies. The incidence of anti-Toxoplasma antibodies in SLE sera did not differ in comparison with that in the normal population. Our data suggest that subacute and chronic toxoplasmosis do not play essential roles in generating the antibodies that are important to the pathogenetic mechanism operating in SLE.
Adult↗
Acute-phase response in early refractory rheumatoid arthritis: long-term follow-up study.
In order to investigate the role of the acute-phase response in early rheumatoid arthritis (RA), we followed the changes of alpha 1-acid glycoprotein (AGP), alpha 1-antitrypsin (AT) and alpha 1-antichymotrypsin (ACT) in the sera of 25 patients with refractory rheumatoid arthritis (RA) during the first 3 years of the disease. Serum levels of AGP, ACT and AT were measured using rocket immunoelectrophoresis, and AGP, ACT and AT microheterogeneities were performed using two-dimensional immunoelectrophoresis with concanavalin A (Con A) as ligand. On average, serum levels of AGP, ACT and AT proteins were higher at the onset of the disease as compared with healthy controls. After 3 years, a significant decrease in serum levels of all three acute-phase proteins (APPs) was observed, but only in patients without anatomical progression was this decrease statistically significant. At the beginning of the study, only the AT reactivity coefficient (RC) was decreased in comparison with healthy subjects. However, after 3 years of disease, AGP, ACT and AT RCs all decreased. This investigation provided two new observations. The first is that only AT RC is significantly lower in comparison with normal values at the beginning of RA, whereas AGP RC and ACT RC remain within the normal range of values; a decrease in AGP RC and ACT RC appeared later. The second observation is that the highly elevated levels of APPs at the onset of RA decrease during the course of the disease. Moreover, this decrease does not depend on the disease activity, but a relationship with radiological progression was shown.
Acute-Phase Proteins↗
Does IgA-alpha1 antitrypsin complex correlate with IgM, IgG and IgA rheumatoid factor in early rheumatoid arthritis?
This study was undertaken to determine whether the rheumatoid factor (RF) isotypes affect the level of IgA-AT complex in early rheumatoid arthritis. IgA-AT complex and IgM, IgG, and IgA RF were evaluated using a double antibody enzyme-linked immunosorbent assay (ELISA) in sera of 83 (61 women and 22 men) patients. The mean level of the complex was higher in RA patients as compared with the control group (0.60 +/- 0.41 U vs 0.19 +/- 0.11 U, p < 0.05). The IgA-AT complex values exceeding the norm were found in 19 of 83 RA cases (23%), mainly in patients non-treated with DMARDs. IgM RF values judged as positive were present in 53 (64%), IgG RF in 55 (66%), and IgA RF in 56 (67%) patients. Higher RF values of IgM and IgG, but not those of IgA class, were found more frequently in patients with elevated IgA-AT levels. A good correlation was established between IgA and IgM RF (r = 0.61, p < 0.01), but not between IgA and IgG, or IgM and IgG RF in the group of patients under study. However, we did not find any significant correlation between isotypes of RF and parameters of the disease activity.
Adult↗
[Immunotherapy in rheumatoid arthritis of joints].
The etiology of rheumatoid arthritis (RA) is still unknown. Among the pathogenic mechanisms being discussed, the antigen recognition seems to be of great importance. Probably the "abnormal" interaction between the presented peptide of undefined nature with CD4 T-cell, triggers the pathological events. Immunosuppressive drugs, affecting antigen presentation, are in common use in the treatment of RA. We discuss the effects of alkylating agents, antimetabolites and other immunomodulatory procedures on the course of the disease.
Arthritis, Rheumatoid↗
Immunological studies in patients with rheumatoid arthritis treated with methotrexate or cyclophosphamide.
One-hundred-and-two-patients (pts) with rheumatoid arthritis (RA) were observed for 12 months. Forty-eight pts were treated with a weekly low-dose of methotrexate (MTX), 23 pts with cyclophosphamide (CTX) (eight pts with one single intravenous dose, and 15 pts orally with a single daily dose), and 31 pts with nonsteroidal antiinflammatory drugs (NSAID) only. In all individuals acute phase response, i.e., C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP) serum levels, and AGP microheterogeneity using affinoimmunoelectrophoresis with concanavalin A were evaluated. The phenotype of lymphocytes isolated from peripheral blood was characterized using immunofluorescence technique. Following treatment the increased level of CRP significantly decreased whereas AGP serum level remained unchanged. Among the patients, microheterogeneity of AGP expressed as reactivity coefficient (RC) was lower before treatment when compared with 17 controls (0.95 +/- 0.23 vs. 1.35 +/- 0.15, p < 0.01). After 12 months of MTX therapy AGP-RC rose significantly (1.19 +/- 0.13, p < 0.01). No changes were observed in AGP-RC levels in CTX and NSAID treated individuals. No significant differences were observed in the percentage of CD3+, CD4+, and CD8+ cells in all the patient groups, except in CTX intravenously treated patients. In this group of patients a decrease of CD4+ cells was noticed (60.1 +/- 11.5% and 43.8 +/- 12.5% before and after treatment respectively -p < 0.01). The percentage of CD19 positive cells decreased significantly during 12 months of treatment with MTX and CTX. The percentage of activated T cells (CD25+ cells and HLA-DR+ cells) remained unchanged in MTX treated patients and was reduced in both CTX groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗