The absence of evidence suggesting that systemic lupus erythematosus is a zoonosis of dogs.
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Biomedical subjects
Publications and source records attributed to A Wiik.
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A sensitive crossed radioimmunoelectrophoretic method (CRIE), originally developed to study lymphocyte-associated beta 2-microglobulin (beta 2m), was applied in the study of serum beta 2m in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In six of seven patients with SLE and nineteen of twenty-seven patients with RA a considerable electrophoretic heterogeneity of serum beta 2m was found. In addition to the normally seen symmetric beta 2m precipitate, a beta 2m precipitate exhibiting complete immunochemical identity was found in the alpha-electrophoretic region. Binding of isolated 125I-labelled beta 2m to the abnormal precipitate was demonstrated in crossed immunoelectrophoresis. After gel filtration of sera exhibiting the above-mentioned beta 2m binding, all beta 2m was eluted in low molecular weight fractions corresponding to free beta 2m. By application of appropriate antisera and a glycoprotein-binding lectin in intermediate gels in CRIE, it was shown that the possible beta 2m-binding ligand is not an antibody, not a major constituent of normal human serum, and not unmodified HLA alloantigen. The abnormality was not restricted to patients with high disease activity but was found more frequently and was more pronounced (mean score 1.6 arbitrary units against 0.57 arbitrary units, P less than 0.01) in such patients. Thus our data exclude the possibility that autoantibodies to beta 2m were present in serum from patients with SLE and RA.
The mechanism of in vitro hyposensitization was examined in isolated rat mast cells. Surface distribution of immunoglobulin was examined by immunofluorescence technique. Hyposensitization could be ascribed neither to changes in the distribution of surface immunoglobulins nor to capping or shedding phenomena. The distribution of cell-bound antigen and the number of antigen-positive cells (patch-bearing cells) was not changed by hyposensitization. The binding of antigen to surface Ig was quantitated by I125-labelled antigen. In rats sensitized to two different antigens, hyposensitization of the mast cells with one of these inhibited the subsequent histamine release induced by either of the two antigens, whereas no changes were observed in the antigen binding capacity. The present investigation indicates that the mechanism of in vitro hyposensitization is the result of events secondary to the initial binding of antigen to the mast cell surface immunoglobulin.
A new experimental design was developed to study the value of clinical parameters of disease activity in patients with rheumatoid arthritis. Ten patients with classical rheumatoid arthritis were examined by five senior doctors in a department of medical rheumatology. In spite of an attempt to make the clinical examination as uniform as possible the inter-observer variation among the doctors was greater than the variation among the patients, for the following parameters: joint pain at rest, joint tenderness and joint swelling. An acceptable inter-observer variation in relation to patient variation was found for 1) a combined registration of joint pain at rest or on movement, 2) duration of morning stiffness, 3) grip strength, 4) subjective well-being as indicated on a visual analogue scale, 5) fingertip--palm distance, and 6) maximum flexion-extension in elbows, wrists and knees. The variation from morning to afternoon and from day to day was negligible. It is concluded that registration of elaborated articular scores is useless in the daily routine in rheumatological departments when different doctors examine the patients.
The medical history was obtained and a physical examination carried out--in addition to an immunological investigation of the blood and skin--on 11 dogs in the ownership of patients with systemic lupus erythematosus (SLE). The results were compared with those obtained from a control group and it was found that they do not support the hypothesis that SLE is a zoonosis.
Eleven cystic fibrosis (CF) patients chronically infected in the lungs with mucoid Pseudomonas aeruginosa and presenting multiple precipitins in serum against this bacterium (CF + P) and 10 CF patients without P. aeruginosa infection (CF-P) had their serum and sputum sol phase specimens examined for antibodies of the IgA and IgG classes against surface antigens of P. aeruginosa by means of an indirect immunofluorescence technique. Both the IgA and IgG antibody titres demonstrated in serum and sputum of the CF + P patients were significantly higher than in those of the CF-P patients (p less than 0.01). The titre of IgA antibodies in the sputum was higher than in serum in 3 cases indicating local pulmonary production of specific IgA antibodies. The role of the demonstrated antibodies in the local pulmonary immune defense mechanisms and the possible patogenesis of the pulmonary tissue damage in CF patients is discussed.
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The Kveim reaction was studied in vivo in 50 patients with sarcoidosis. Commonwealth Serum Laboratories Kveim material and a new Danish Kveim material gave 14 and 8 positive reactions respectively, as well as 6 and 8 equivocal reactions. Forty-six of the patients were also tested in vitro for cell mediated immunity to the Danish Kveim material, using both the leucocyte migration agarose technique and the capillary technique. No significant migration inhibition or stimulation were found. A tuberculin skin test was performed in 49 of the patients, and in 45 a dinitrochlorobenzene sensitivity titer was determined. Both tests revealed a depression of the cell mediated immunity. The serum levels of immunoglobulins IgG, IgA, IgM, IgD, and IgE were determined. The serum of each patient was also examined to determine if organ-non-specific and granulocyte-specific antinuclear factors of IgG class, antibodies against native DNA, rheumatoid factor, mitochondrial antibodies, antibodies against thyroid cytoplasm, and parietal cell antibodies were present. IgG levels were above normal in 28 patients; IgE was above normal in 10 patients, 4 of whom were atopics or had an atopic disposition. Organ-non-specific antinuclear factors were present in 17 patients.
One hundred patients with juvenile chronic arthritis (JCA) were studied with respect to granulocyte-specific and organ-nonspecific antinuclear antibodies (GS- and ON-ANA) in relation to clinical features of disease. Seventy-two were girls and 28 boys. Sixty-seven patients had IgG ANA, 31 IgM, 10 IgA, 6 IgD, 19 IgE and 35 had ANA, which fixed complement C3. Sixteen of 17 sera containing IgG GS-ANA were from girls. The prevalence of IgG GS-ANA increased with the number of joints affected. No patient with the acute febrile type of the disease had IgG GS-ANA or CS fixing ANA. The prevalence of IgG ON-ANA did not differ significantly in the mono-, pauci-, polyarticular and acute febrile types of JCA. Patients showing clinical activity more frequently had IgG and IgM ANA and C3 fixing ANA. The high titers of ANA were most often seen in girls. Chronic uveitis occurred in 10 of the patients and IgG ANA were present in sera from all of these.
Sera from 21 rheumatoid arthritis patients with accompanying neutropenia (less than or equal to 2000 neutrophils/microliter) and 45 rheumatoid arthritis patients without neutropenia were studied for the occurrence of IgD granulocyte-specific antinuclear antibodies. Such antibodies were found in 67 per cent of the neutropenic and 18 per cent of the non-neutropenic cases (p less than 0.001). The titres of IgD granulocyte-specific antinuclear antibodies varied independently of the titres of IgD and complement-fixing granulocyte-specific antinuclear antibodies, but showed some covariation with granulocyte-specific antinuclear antibodies of the IgA and IgM classes most probably reflecting a broad polyclonal antibody response to phagocyte nuclear antigens in the serologically highly active neutropenic cases. Gel filtration studies on selected sera containing IgD granulocyte-specific antinuclear antibodies indicated participation of these antibodies in immune complexes. It is thus possible that IgD granulocyte-specific antinuclear antibodies may have some significance for the rheumatoid inflammatory processes.
Antinuclear antibodies (ANA) of the IgE class were studied in sera from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and healthy controls. Sixty per cent of 20 RA patients with neutropenia were found to have IgE granulocyte-specific (GS-)ANA, whereas only 16% of RA patients without neutropenia had IgE antibodies of similar specificity. About 5% in each group of RA patients had IgE organ-nonspecific (ON-)ANA. Eleven of 15 patients with active SLE and only 4 of 20 with inactive SLE had IgE ON-ANA. Sera from five patients with lupus nephritis all contained IgE ON-ANA. None of 100 sera from controls showed presence of IgE ANA. IgE ANA titres in RA and SLE patients correlated to the titres of ANA of the other four immunoglobulin classes. Gel filtration studies at neutral and acid pH of RA sera containing high titres of IgE GS-ANA indicated the presence of these antibodies in immune complexes. Studies of serum cryoprecipitates supported this conclusion. IgE ANA production may be of pathogenetic importance in RA and SLE by eliciting type-I reactions.
In a patient with chronic lymphocytic leukaemia, two M components of the IgGkappa and IgGlambda classes were demonstrated in the serum at the time of diagnosis. The patient was first followed without treatment; after 18 months multiple myeloma developed. At that time, immunofluorescence study of lymphocytes of the peripheral blood showed mainly membrane-bound immunoglobulins (S-Ig) of the IgGkappa class. The bone marrow disclosed a definite predominance of plasma cells with cytoplasmic IgGlambda, suggesting that the two B cell-derived diseases had arisen from two different cell clones. During the development of multiple myeloma, the serum concentration of the M component IgGlambda increased. Concurrently, the M component of IgGkappa gradually disappeared from the serum, and the concentrations of the normal immunoglobulins IgA and IgM declined. Following cytostatic treatment, the concentration of the myeloma-derived M component IgGlambda was halved and simultaneously the M component IgGkappa reappeared in the serum. To our knowledge, this case is the second reported of chronic lymphocytic leukaemia and multiple myeloma indicating development of the two diseases from different cell clones, and the first reported cases with myeloma-induced suppression of M-component secretion from malignant cells.
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Specific HLA antibodies were used to eliminate donor and recipient cells, respectively, from lymphocyte suspensions prepared from the blood of a child who had been transplanted with bone marrow from an HLA-A- and HLA-B-incompatible, HLA-D-compatible donor. About 70% of the lymphocytes were of donor HLA type, the remaining of recipient type. The phytohemagglutinin-responsive lymphocytes were exclusively limited to the lymphocyte population carrying donor-type HLA antigens. Membrane immunofluorescence investigations of the donor and recipient populations showed a low percentage of IgM-positive lymphocytes in the donor population and an extremely high proportion of IgM-positive lymphocytes in the recipient population. About 90% of the donor lymphocytes were T cells, as judged by their capacity to form rosettes between sheep erythrocytes and T lymphocytes; no cells in the recipient cell population expressed this ability.
In biopsies from normal-looking skin, immune complexes in the dermo-epidermal junction zone were found by a direct immunofluorescence technique in 14 of 17 patients with systemic lupus erythematosus, in 6 of 12 patients with rheumatoid arthritis, but in none of 10 patients with temporal arteritis and 25 normal controls. Blood samples were obtained simultaneously from all patients and high titres of IgG organ-nonspecific antinuclear factors with complement-fixing properties were found to be closely related to systemic lupus erythematosus. IgG granulocyte-specific antinuclear factors were related with rheumatoid arthritis, while high concentrations of plasma fibrinogen were characteristic of temporal arteritis. No significant increases or differences in blood values of alpha2-macroglobulin were found between the groups and no correlation was found with deposits in the skin.