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Biomedical subjects

F C Breedveld

Publications and source records attributed to F C Breedveld.

At least 433 records · Page 24Linked to original sources

Mononuclear phagocyte system Fc-receptor function in patients with seropositive rheumatoid arthritis.

Mononuclear phagocyte system (MPS) Fc-receptor function in 20 patients with seropositive rheumatoid arthritis (RA) was investigated using radiolabelled autologous erythrocytes coated with an average of 5,800 molecules of anti-rhesus IgG (E. IgG). Although clearance times (T1/2) of E. IgG tended to be longer in RA patients than those in healthy controls (46 +/- 6 min vs 38 +/- 5 min, mean +/- s.e.m., P = 0.38), this did not reach statistical significance. Liver spleen uptake ratios (LS ratios) were increased in patients with RA (13/100 +/- 1/100 vs 7/100 +/- 1/100, P less than 0.05). There was no correlation of T1/2 or LS ratios with articular disease activity, vasculitis, ESR, IgM containing immune complex levels or Clq-binding immune complex levels. Although Clq-binding immune complex levels were significantly higher in patients with vasculitis than in those without (P less than 0.01), T1/2 and LS ratios did not differ in these two groups of patients. The T1/2 and LS ratios of E.IgG did not reveal a defect in MPS Fc-receptor function and did not correlate with one of the above-mentioned clinical and immunological parameters. We suggest that in order to establish a possible defect in Fc-receptor function correlating with disease activity and immune complex levels in RA patients, soluble immune complexes or immune complex-like material should be used as probes.

Adult↗

Progress in the understanding of inducible models of chronic arthritis.

Definitive information regarding the etiology of most rheumatic syndromes is not available, but studies of several inducible models of chronic arthritis have helped to identify pathogenetic mechanisms in human inflammatory arthritis. Animal models offer an opportunity to analyze morphologic and biochemical changes occurring during the course of an arthritis, probe the role of genetics, and predict the effects of therapeutic interventions in the human disease. This article describes some contributions obtained from animal studies.

Animals↗

Factors influencing the incidence of infections in Felty's syndrome.

To identify clinical and laboratory risk factors for the susceptibility to infections in Felty's syndrome, 46 patients were studied prospectively during a total number of 431 periods of three months ("patient-quarters"). The incidence of infections increased significantly with polymorphonuclear leukocyte (PMN) counts below 0.1 X 10(3)/mm3 (less than 0.1 X 10(9)/L). At PMN levels over 0.1 X 10(3)/mm3 (greater than 0.1 X 10(9)/L), no association was found between PMN counts and the incidence of infections. Other factors found to be associated with an increased incidence of infections were severe disability, skin ulcers, glucocorticosteroid dose, monocyte counts, hypocomplementemia, and high levels of circulating immune complexes. The activity of the rheumatoid arthritis, erythrocyte sedimentation rate, hemoglobin concentrations, and lymphocyte counts were not associated with increased incidence of infections.

Arthritis, Rheumatoid↗

Phagocytosis and intracellular killing of Staphylococcus aureus by polymorphonuclear cells from synovial fluid of patients with rheumatoid arthritis.

The phagocytosis and intracellular killing by synovial fluid (SF) polymorphonuclear cells (PMN) of 10 patients with rheumatoid arthritis was studied. PMN phagocytosis was assessed by morphologic and microbiologic methods and intracellular killing was measured independently of continuous phagocytosis of Staphylococcus aureus. Phagocytosis of S aureus by SF PMN or peripheral blood (PB) PMN was as effective in the presence of synovial fluid as in the presence of serum. On average, SF PMN ingested S aureus opsonized with synovial fluid and serum more efficiently than patient or donor PB PMN did. Enhanced ingestion of S aureus was associated with increased expression of C3 receptors on the membrane of SF PMN. In the presence of heat-inactivated synovial fluid, the capacity of SF PMN to ingest S aureus was greater than that of patient or donor PB PMN. Under these conditions, phagocytic activity was correlated with Fc receptor expression. SF PMN was found to be as active in killing S aureus as PB PMN from healthy donors.

Analysis of Variance↗

Coronary arteritis complicating rheumatoid arthritis.

The case is described of a patient with rheumatoid arthritis (RA) who developed heart failure and vasculitis and died of a myocardial infarction. Autopsy showed vasculitis of several major epicardial coronary arteries. Coronary arteritis in a patient with RA is seldom diagnosed during their lifetime but should be suspected when such a patient develops ischaemic heart disease.

Aged↗

Immunogenetic heterogeneity of rheumatoid arthritis.

Association of HLA-DR4/Dw4 with rheumatoid arthritis (RA) is well established, but conflicting data exist on a possible association with the severity of the disease, including its extra-articular manifestations. In order to investigate whether a subgroup of RA is preferentially associated with DR4, HLA typing was performed in two groups of patients with severe extra-articular manifestations (Felty's syndrome and histologically proved leucocytoclastic vasculitis), patients with severe joint destruction (seropositive and seronegative), a group with only mild joint destruction, and in healthy controls. The frequency of HLA-DR4 was significantly raised in all patient groups compared with that in healthy controls. The two groups with severe extra-articular manifestations, however, both had a DR4 frequency of 92%, which was significantly (p = 0.002) higher than the 62.7% found in the remaining patients. No significant differences were observed between severe or mild joint destruction and seropositivity or seronegativity in the groups without the above-mentioned extra-articular manifestations. From these data we concluded that DR4 is preferentially associated with severe extra-articular disease manifestations of RA. This observation provides an immunogenetic basis for the disease heterogeneity and for the immunological analogy between RA and leprosy.

Adult↗

Immune complexes and the pathogenesis of neutropenia in Felty's syndrome.

The effect of the injection of serum from patients with rheumatoid arthritis (RA) and Felty's syndrome (FS) into mice on the number of circulating polymorphonuclear cells (PMN) was studied. The number of circulating PMN dropped to 61% (range 34-98%) of the initial counts after the injection of FS serum. This phenomenon was observed less frequently after injection of RA serum. In contrast, injection of serum from healthy controls always resulted in an immediate increase in the number of circulating PMN. No decrease in PMN counts was found after injection of FS sera pretreated with polyethylene glycol to precipitate immune complexes (IC). Gel filtration of FS sera on Sepharose 4B showed that the effect on the PMN counts in mice did not coincide with the 7S peak but occurred only in fractions containing larger material. Serum fractions from FS patients that contained IC were more active in producing neutropenia than the corresponding fractions from patients with RA. Microscopic and immunohistochemical examination of the organs from mice injected with FS serum showed sequestration of PMN and deposition of human IgG, IgA, and IgM in the vascular bed of the lungs. These results indicate that the interaction between PMN and IC of patients with FS leads to sequestration of PMN in mice and suggests that this interaction in humans may have a role in the pathogenesis of FS.

Aged↗

Distal renal tubular acidosis in polyarteritis nodosa.

Distal renal tubular acidosis developed in a patient with polyarteritis nodosa. The acidosis gradually disappeared, together with most of the other symptoms of systemic vasculitis, after treatment with prednisone and cyclophosphamide. Tubular function test results in this patient suggested that the mechanism underlying the acidification disturbance was acid back-leakage.

Acidosis, Renal Tubular↗

Phagocytosis and intracellular killing by polymorphonuclear cells from patients with rheumatoid arthritis and Felty's syndrome.

The present in vitro study concerned the phagocytosis and intracellular killing by polymorphonuclear cells (PMN) of 5 patients with rheumatoid arthritis (RA) and 12 patients with Felty's syndrome (FS). PMN phagocytosis was assessed by microbiologic and morphologic methods, and intracellular killing was measured independently of continuous phagocytosis of viable bacteria (Staphylococcus aureus). PMN from patients with RA or FS ingested S aureus opsonized with immunoglobulins and complement as effectively as did PMN from healthy donors. However, the capacity of patient PMN to ingest S aureus opsonized with sera lacking complement activity, e.g., heat-inactivated donor serum and the sera of 2 patients with FS, was lower than that of healthy donor PMN. This decreased ingestion is associated with diminished expression of Fc receptors on the membrane of PMN from patients who have RA or FS. As with sera lacking complement activity, decreased capacity to ingest S aureus was observed after preloading donor PMN with immune aggregates, which also decreased the expression of Fc receptors. PMN from patients with RA or FS were found to be as active in killing S aureus as cells from healthy donors.

Adult↗

Felty syndrome: autoimmune neutropenia or immune-complex-mediated disease?

Immunofluorescence on polymorphonuclear cells (PMN) of patients with Felty syndrome (FS) revealed increased amounts of IgG, IgA, and IgM bound to the PMN surface compared with PMN of patients with rheumatoid arthritis alone. A positive correlation was found between the score for surface-bound immunoglobulins on FS-PMN and the results of the Clq binding assay in FS sera. After preincubation with sera from 20 patients with FS, immunofluorescence on PMN from healthy controls (HC) showed that these cells had bound IgG, IgA, and IgM. However F(ab')2 fragments of IgG from FS sera did not bind to PMN, although the antigen-binding reactivity of the F(ab')2 fragments was maintained as shown by control experiments. Immunoglobulins eluted from FS-PMN failed to bind to HC-PMN, whereas the corresponding IgG of patients with autoimmune neutropenia was bound. Gel filtration of FS sera on Sepharose 4B showed that the binding of IgG in FS sera to PMN did not coincide with the 7S peak but occurred mainly in fractions containing larger material. No binding of IgA and IgM to HC-PMN was found after incubation with FS sera pretreated with polyethylene glycol (PEG) to precipitate immune complexes. These results indicate that in sera of patients with FS the PMN-binding reactivity of IgG, IgA, and IgM is due to the binding of immune complexes containing these immunoglobulins and not to presence of autoantibodies directed to antigens on the neutrophil surface.

Antigen-Antibody Complex↗

Rapidly progressive glomerulonephritis with glomerular crescent formation in rheumatoid arthritis.

Systemic vasculitis is a well-known complication of rheumatoid arthritis (RA). Rapidly progressive glomerulonephritis is commonly associated with vasculitis syndromes but rarely found in RA. This report describes two RA patients with complicating systemic vasculitis who developed rapidly progressive glomerulonephritis with glomerular crescent formation. One recovered after treatment with corticosteroids and cytostatic drugs and the other died of severe systemic vasculitis despite similar therapy.

Adrenal Cortex Hormones↗

High dose intravenous gamma globulin for Felty's syndrome.

High dose intravenous gamma globulin (IV-IgG) was given to 5 patients with Felty's syndrome. The neutrophil count did not change with IV-IgG therapy and no side effects were encountered. We conclude that neutropenia in Felty's syndrome is not comparable to autoimmune hemocytopenia with respect to the response to IV-IgG.

Aged↗

Fc receptors on granulocytes from patients with rheumatoid arthritis and Felty's syndrome.

Receptors for the Fc part of IgG on polymorphonuclear cells (FcR) of patients with rheumatoid arthritis (RA), Felty's syndrome (FS) and healthy controls (HC) were studied by means of a rosetting technique with rabbit IgG coated ox erythrocytes. When cold isolated polymorphonuclear cells (PMN) were incubated at room temperature the percentage of rosette forming PMN (RF-PMN) from HC was more than twice that measured directly after isolation at 4 degrees C. The same phenomenon was observed for PMN from patients with RA although the RF-PMN increased by only 1/3. In contrast warming of PMN from patients with FS did not influence the RF-PMN. The presence of surface bound immunoglobulins and intracytoplasmic immunoglobulins was measured by immunofluorescence and appeared to be inversely related to the RF-PMN. A good correlation between the results of the C1q binding assay (C1qBA) and the immunofluorescence score was observed but no correlation existed between the C1qBA and the RF-PMN. These results indicate that the number of PMN expressing FcR in patients with RA and FS is decreased presumably because of the phagocytosis of immune complex like material. The decrease in the availability of FcR may influence the functions of the PMN.

Antigen-Antibody Complex↗

C3 receptors on granulocytes from patients with rheumatoid arthritis and Felty's syndrome.

The expression of receptors for the third component of complement (C3R) on polymorphonuclear cells (PMN) from patients with rheumatoid arthritis (RA) or Felty's syndrome (FS) and healthy controls (HC) was studied by means of a rosetting technique using ox erythrocytes coated with rabbit IgM and mouse complement. The percentage of rosette forming PMN (RF-PMN) was found to be increased in patients with FS (59%) and patients with RA (47%) compared to HC (18%), when measured directly after cold isolation of PMN. Incubation at 37 degrees C of cold isolated cells increased the percentage of RF-PMN in all three groups, although the values were significantly higher during the first 45 min of incubation in both patient groups. When incubated with serum from patients with FS at 37 degrees C, cold isolated donor PMN formed significantly more rosettes than after incubation with donor serum. This increase was shown to be due to the presence of circulating immune complexes in the patient sera and could be mimicked by incubating donor PMN with aggregated human IgG. As a result of these experiments it was demonstrated that the increased percentages of PMN with C3R in patients with FS or RA are most likely caused by a previous in vivo activation of PMN by immune complexes. The possible effect of such an increase in C3R expression in relation to PMN function in these patients is discussed.

Antigen-Antibody Complex↗

The clinical significance of macrocytosis.

The cause of macrocytosis (mean corpuscular volume (MCV) greater than or equal to 105 fl) was investigated over a period of 16 months in the 70 known cases of +/- 4000 patients seen by the Department of Internal Medicine. By means of simple laboratory investigations the cause of elevated MCV was found in more than 90% of the cases. We found vitamin B12 or folic acid deficiency in 27 patients, alcohol abuse in 18, chronic persistent hepatitis in 2, hematological (pre-) malignancy in 9, hemolysis in 4, hypothyroidism in 2, and a drug effect in one patient. In 6 cases the elevated MCV could not be explained. Macrocytosis, a frequent finding that is not related to the hemoglobin concentration, is an indicator of serious pathology. The MCV level can be used to differentiate between the diagnostic categories. Only 21 patients (30%) had megaloblastic erythropoiesis that was difficult to recognize in the peripheral blood. Among the findings at routine laboratory investigations an elevated MCV may be the only indicator of vitamin deficiency, preleukemia or alcoholism.

Alcoholism↗