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Biomedical subjects

C G Kallenberg

Publications and source records attributed to C G Kallenberg.

At least 253 records · Page 14Linked to original sources

Cutaneous reactions to captopril. Predictive value of skin tests.

Cutaneous reactions associated with captopril treatment occurred in fifteen out of eighty-nine patients (17%). Dose reduction invariably led to improvement of the reaction but later recurrences were frequent (six patients). In four out of the fifteen patients captopril withdrawal ultimately was necessary. Skin tests and in vitro lymphocyte transformation tests with captopril were performed in these fifteen patients and also in nine captopril-treated control patients without adverse reactions. Positive epicutaneous skin tests were observed in five out of the fifteen patients including the four in whom captopril had to be withdrawn, but in none of the controls. Intracutaneous skin tests were positive in ten of the patients with cutaneous reactions and in two control patients. Captopril-induced in vitro lymphocyte transformation occurred in most patients with cutaneous reactions whereas in control patients captopril suppressed the in vitro lymphocyte proliferative response. Skin biopsies revealed histologic changes consistent with lymphocytic vasculitis. We conclude that epicutaneous skin tests with captopril are helpful in predicting the necessity of captopril withdrawal.

Adolescent↗

Steroid-responsive interstitial pulmonary disease in systemic sclerosis. Monitoring by bronchoalveolar lavage.

We describe a 38-year-old woman with systemic sclerosis of recent onset and progressive dyspnea. Studies of pulmonary function revealed a restrictive ventilatory disorder with decreased diffusing capacity. Interstitial fibrosis and infiltration with lymphocytes and plasma cells with formation of follicles were observed in the lung biopsy. Analysis of fluid from bronchoalveolar lavage showed an increase in the total number of cells, with a relative increase in neutrophils. Also, the relative amount of the immunoglobulins, IgG and IgM, was increased. During corticosteroid treatment, rapid improvement of pulmonary volumes occurred, together with disappearance of neutrophils and an increase in the percentage of lymphocytes in the lavage fluid. Later on, the total number of cells in the fluid from bronchoalveolar lavage and the percentage of lymphocytes reached normal values. Bronchoalveolar lavage may be of value in assessing and monitoring pulmonary disease in patients with systemic sclerosis.

Adult↗

Decreased filtration fraction during active proliferative lupus nephritis: relation to disease activity and reversibility of renal function.

Nine consecutive patients with systemic lupus erythematosus (SLE) were studied longitudinally for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during ten exacerbations of severe proliferative glomerulonephritis. At the onset of exacerbation, GFR decreased significantly whereas ERPF did not fall; the latter even increased in some patients. As a consequence mean filtration fraction (FF), the ratio of GFR and ERPF, fell from 0.20 to 0.10. At maximum exacerbation, both GFR and ERPF had decreased without change in FF. During remission FF rose to pre-exacerbation values as a result of increase in GFR without change in ERPF. We conclude that changes in FF reflect changes in renal haemodynamics in patients with SLE and active proliferative glomerulonephritis. Determination of FF may be of some value in assessing renal disease activity and the degree of reversibility of renal function in those patients.

Adult↗

Reticuloendothelial Fc receptor function in SLE patients. I. Primary HLA linked defect or acquired dysfunction secondary to disease activity?

Reticuloendothelial system (RES) Fc receptor-mediated immune clearance was measured in 18 patients with systemic lupus erythematosus (SLE). Only two patients, with major disease activity, had a prolonged T 1/2 of the blood disappearance curve of injected IgG coated red cells in comparison to 22 healthy controls. Circulating immune complexes (CIC) were studied with three methods: PEG precipitation, C1q-ELISA and the indirect granulocyte phagocytosis test (IGFT). The T 1/2 of the blood disappearance curve related significantly to the IGFT (r = 0.55, P less than 0.05) and not to the PEG and C1q-ELISA test. Although HLA-DR3 phenotype frequency was significantly increased in our SLE population (P less than 0.05), it was not related to Fc receptor function. Similarly, HLA-DR2 phenotype was not related to RES Fc receptor function. These data do not support the concept that a genetic HLA linked defect in reticuloendothelial Fc receptor function is a primary cause of SLE, predisposing the inflicted individual to immune complex deposition. However, Fc receptor-mediated immune clearance seems to be related to disease activity itself and to levels of CIC.

Adolescent↗

Reticuloendothelial Fc receptor function in SLE patients. II. Associations with humoral immune response parameters in vivo and in vitro.

We studied the relationship between reticuloendothelial Fc receptor function and some parameters of the humoral immune response in vivo and in vitro in 18 SLE patients. Fc receptor-mediated immune clearance correlated remarkably well with (a) a decrease of antigen specific IgG after immunization with a primary test antigen (alpha-Helix pomatia haemocyanin) (P less than 0.01) and (b) the spontaneous IgG release in vitro of B cells obtained from peripheral blood (P less than 0.01). These two parameters were significantly interrelated. Reticuloendothelial Fc receptor function was not related to serum IgG levels. The study provides evidence for an association between polyclonal B cell activation and Fc receptor-mediated immune clearance in SLE patients. The possible nature of this association is discussed.

Adult↗

Lymphocyte characteristics and function in paroxysmal nocturnal haemoglobinuria.

In six patients with paroxysmal nocturnal haemoglobinuria (PNH) lymphocyte studies were performed to investigate whether the observed immunological dysfunction could be ascribed to a defect in lymphocytes as result of the PNH characteristics, or to an imbalance between T-cell subsets. The PNH characteristics were studied by means of the effect of serum and acidified serum on Indium111-oxine labelled lymphocytes. No increase in release of Indium111-oxine was found when lymphocytes were exposed to acidified sera. Thus a complement mediated lymphocyte lysis in PNH could not be demonstrated. T-cells were defined by monoclonal antibodies, directed at total T-cells (OKT3), helper T cells (OKT4) and suppressor/cytotoxic T-cells (OKT8). In two of the six patients a decreased proportion of OKT3 cells was found, while a significantly depressed ratio of OKT4/OKT8 cells was present in the whole group. No obvious correlation was found between a functional assay - the concanavalin-A suppressor cell activity - and the ratio of OKT4/OKT8 positive cells. It is concluded that the PNH characteristics could not be demonstrated in the lymphocytes; and that the immunological dysregulation in PNH may be ascribed to an imbalance of T-cell subsets, while a decreased number of monocytes, defined by the monoclonal antibody OKM1, may contribute to this defect.

Antibodies, Monoclonal↗

Human fibroblasts, a convenient nuclear substrate for detection of anti-nuclear antibodies including anti-centromere antibodies.

Human fibroblast monolayers were applied as a nuclear substrate in indirect immunofluorescence for the detection of anti-nuclear antibodies (ANA). Comparison of the results obtained with this substrate and with conventional rat liver sections led to the conclusion that the application of human fibroblast monolayers as a substrate has the following advantages: 1) better recognition of the distinct nuclear staining patterns; 2) more convenient serum titrations, since a cryostat is not needed and twelve tests can be performed on one slide; 3) detection of significantly higher ANA titres in sera from patients with SLE and MCTD; 4) recognition of a type of ANA that was not detected on rat liver sections. These latter antibodies produced a discrete speckled pattern of fluorescence, which was completely lost after acid elution of the fibroblasts. Using HEp-2 cells in metaphase, it was shown that the antibodies were directed against the centromere regions of the chromosomes. These anti-centromere antibodies were detected in sera from patients with severe Raynaud's phenomenon. Underlying disorders were scleroderma (8 patients, 5 of them with CREST syndrome), Sjögren's syndrome (2 patients), and Raynaud's phenomenon in combination with a few symptoms of connective tissue diseases without fulfilling the criteria for a specific disease (5 patients).

Adolescent↗

B cell activity in systemic lupus erythematosus: depressed in vivo humoral immune response to a primary antigen (haemocyanin) and increased in vitro spontaneous immunoglobulin synthesis.

B lymphocyte studies, in vivo and in vitro, were performed in 28 patients with systemic lupus erythematosus (SLE). After immunization with the primary test antigen haemocyanin, a decreased antigen specific humoral immune response was observed for all three Ig classes, irrespective of disease activity or the use of corticosteroids. Levels of antibodies against (recall) viral and nuclear antigens were increased during active disease. The in vitro spontaneous production of IgM and IgG, determined in the supernatant of 8 days cultures by ELISA, was highly increased in patients with active disease (reversely correlated with levels of complement C3, r = 0.74). Pokeweed mitogen-induced synthesis was decreased in all patients. The distribution of T cell subsets (OKT3, Leu 3a and OKT8 positive cells) was not different from controls, irrespective of disease activity. It is concluded that the primary humoral immune response is decreased in SLE, whereas a polyclonally activated B cell appears to be present. The normal T cell subset distribution does not support the primary role of the cell in the state of hyperactivity of the B cell.

Adolescent↗

In vivo antinuclear antibodies (ANA) in biopsies of normal skin: diagnostic significance and relation to serum ANA.

Epidermal nuclear Ig deposition (in vivo ANA) was observed in 54 out of 1,717 skin biopsy specimens routinely examined by immunofluorescence. Patterns were speckled (26), homogeneous (24), or nucleolar (3). The speckled pattern was sensitive (94%) but less specific (58%) for mixed connective tissue disease. The homogeneous pattern, found in SLE and scleroderma, was neither sensitive nor specific for those diseases. The nucleolar pattern was infrequently observed in scleroderma. Patterns of in vivo ANA and serum ANA did not correspond in 24% of patients. In vivo ANA were restricted to IgG class; serum ANA in 78% of patients were also of IgM class and in 37% of IgA class. The discrepancies between in vivo and serum ANA suggest that in vivo ANA is a true in vivo phenomenon.

Adult↗

Antinuclear and antinative DNA antibodies during captopril treatment.

Antinuclear antibodies (ANA) developed in 13 out of 78 patients treated with captopril for a mean period of 11 months. In another 11 patients, who were ANA-positive before captopril therapy, no increase in ANA titer was observed during treatment. Neither the development nor the presence of ANA before captopril treatment were associated with (drug-induced) lupus erythematosus or increased incidence of clinical side-effects, although development of ANA was accompanied by a serum-sickness-like syndrome in one patient. The ANA were mainly of the IgM class, did not fix complement and were transiently present. In three patients, antinative DNA antibodies, exclusively of IgM class and not complement-fixing, were transiently present without clinical signs of systemic lupus erythematosus, although recurrence of these antibodies was associated with slight proteinuria in one of them.

Adult↗

Antinuclear antibodies in patients with Raynaud's phenomenon: clinical significance of anticentromere antibodies.

Antinuclear antibodies (ANA) were detected in the sera of 73 out of 138 patients (53%) referred to us because of Raynaud's phenomenon. When ANA were found, systemic manifestations were likely to be present. The use of human fibroblast monolayers as a nuclear substrate allowed differentiation of several fluorescence patterns, including the discrete speckled variety produced by anticentromere antibodies. These antibodies were detected in the sera of 7 out of 10 patients with CRST syndrome (70%), in 7 out of 40 patients with scleroderma (18%), all without kidney-involvement, in one patient with Sjögren's syndrome and severe Raynaud's phenomenon, and in 7 patients with Raynaud's phenomenon associated with a few symptoms of a connective tissue disease (especially scleroderma). ANA testing on tissue culture monolayers in Raynaud's phenomenon appears to be of value in predicting systemic disease manifestations and the presence or possible future development of distinct clinical patterns, especially the CRST syndrome.

Adolescent↗

Increased frequency of B8/DR3 in scleroderma and association of the haplotype with impaired cellular immune response.

Twenty-eight patients with scleroderma were typed for 40 HLA antigens. A highly significant increase in the frequency of HLA-B8 and HLA-DR3 was observed, which was not related to the severity of the disease. In vitro lymphocyte stimulation tests were performed in 26 patients. In addition, humoral and in vitro cellular immune responses to a primary test antigen were measured in 12 of them. Although the group of scleroderma patients as a whole had an impaired cellular response, only the B8/DR3+ patients had a strongly depressed response, whereas the immune response of the others was normal. These findings suggest an association of the haplotype B8/DR3 with impaired cellular immunity.

Adolescent↗

Immune-complex glomerulopathy in patients treated with captopril.

Renal biopsies were performed on 13 patients treated with captopril. In 4 patients findings indicated an early stage of membranous glomerulopathy (MGP). In the other patients electron microscopy showed scanty small subepithelial deposits and immunofluorescence revealed a patchy granular pattern along the glomerular basement membrane. One of the 4 patients with MGP presented with nephrotic syndrome and another with serum-sickness-like syndrome. None of the other patients, including 2 with MGP, had proteinuria or deterioration of renal function. Thus captopril may be associated with the development of immune-complex glomerulopathy.

Adolescent↗