Immunoglobulin deposits in the dermo-epidermal junction zone. Nosographic occurrence in a number of medical diseases.
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Biomedical subjects
Publications and source records attributed to H Permin.
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An account is given of chronic diphenyl hydantion (DPH) encephalopathy in 21 mentally retarded epileptics with increasing psychomotor deterioration, choreiform hyperkinesia, deposits of immunoglobulins in the skin, and changes in serum immunoglobulins. Three months after withdrawal of DPH the condition proved partially reversible, from the clinical as well as laboratory point of view. Eleven patients have been followed for 1 year after discontinuation of DPH, and the findings were largely unchanged from the 3-month follow-up examination. Before the drug was withdrawn, seven patients exhibited deposits of immunoglobulins at the dermo-epidermal junction and in vessel walls. At the end of 1 year such deposits were found in only three patients, all of whom were on another antiepileptic drug.
Adenoid tissue was obtained at operation from 27 children admitted for adenoidectomy and from 6 controls. The occurrence of cells with cytoplasmic immunoglobulin was studied semiquantitatively by immunofluorescence microscopy of tissue sections, by which localization, number of cells and class of immunoglobulin were determined. No differences were found between patients and controls. Cells isolated from adenoid tissue were compared with mononuclear leukocytes obtained from the blood. More B lymphocytes were found in the tissue, in particular IgM-carrying cells. This was more pronounced in the patient group. Cells were stimulated in culture with polyclonal activators and microbial antigens. The response of adenoid lymphocytes to Haemophilus influenzae (HI) was high in 7/27 patients; all patients in whom throat culture was positive for HI were low responders.
Sera from 70 patients with Sjogren's syndrome (SS), of whom 40 had primary and 30 secondary SS, were tested for various auto-antibodies of the IgG, IgA and IgM classes. 20% had liver-cell-membrane antibody (LMA), 90% had anti-nuclear antibodies (ANA), 40% salivary-gland antibodies (SGA), 13% anti-mitochondrial antibodies (AMA), 33% smooth-muscle cell antibodies (SMA), 9% skeletal-muscle antibodies (SKA) and only 1% had parietal-cell antibodies (PCA). In addition, 53% had IgM rheumatoid factor and 6 patients with anti-DNA antibodies all had SLE. 64% had increased serum IgG, 24% IgA and 14% IgM. A significantly higher incidence of ANA was found within all three Ig classes in patients with secondary SS. AMA and IgM-rheumatoid factor were also found to be elevated in this group. On the other hand, SGA occurred most frequently in patients with primary SS. LMA was mainly of the IgG class and IgG AMA and SMA were more often present in these patients than in those with a negative LMA reaction. The results of the investigation suggest inter alia that inflammatory liver disease, although not indicated by either the case history, physical examination or biochemical values, is probably present in patients with SS.
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.
Sera from 89 patients with cystic fibrosis (CF) and 88 control persons were examined for the occurrence of rheumatoid factors (RF) of the IgG, IgA and IgM classes by an indirect immunofluorescence method and by the latex fixation slide test. The prevalence of RF-IgG was significantly higher (88%) (p less than 0.0005) among the CF patients than among the control persons (7%), while no difference was found between the two groups with regard to RF of the IgA or IgM classes. Fifty-five of the CF patients had chronic Pseudomonas aeruginosa infection in their lungs and two or more precipitins against these bacteria in their sera determined by crossed immunoelectrophoresis. These CF patients did not differ from the 34 CF patients without chronic P. aeruginosa infection, neither with regard to prevalence nor titer of RFs, but there was a positive correlation between the number of P. aeruginosa precipitins in the 55 chronically infected CF patients and their titers of IgG-RF. Nineteen CF patients were examined also for RFs, antinuclear antibodies (ANA) and anti-DNA antibodies in their sputum sol phase and corresponding sera. RFs were demonstrated in the sputum sol phase from 6 of the patients by the latex fixation test, whereas their sera were negative in this test, possibly indicating a local production of RF. Positive reactions for ANA and anti-DNA antibodies were found in 7 and 10 of the sputa respectively, and in higher titers than in the corresponding sera, also suggesting a local production. Titers of autoantibodies in sputum were low and no difference was found between patients with chronic P. aeruginosa infection and patients without P. aeruginosa infection. The possible role of autoantibodies in the patogenesis of pulmonary tissue damage in CF patients is discussed.
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Antibodies against double-stranded (ds) DNA were demonstrated by an immunofluorescence technique using Crithidia luciliae kinetoplast as antigen, and by means of the Farr technique. Both techniques were used simultaneously in 172 sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), temporal arteritis (TA) and from healthy controls. Comparable results were obtained with the two techniques. SLE patients with active disease had higher titres of IgA antibodies than patients with inactive disease. Of the patients with RA and JRA, 10% had significant titres of dsDNA antibodies. Patients with TA and normal controls had either no dsDNA antibodies in their sera or very low titres without complement-fixing properties.
Basophils from patients with rheumatoid arthritis (RA) respond to RNA, DNA and immune complexes (aggregated IgG) with histamine release. The RNA response was well correlated to the clinical activity of the disease, since histamine liberation was found in all patients with severe activity, whereas no liberation was observed in patients with moderate or quiescent activity. A less significant correlation was obtained with DNA and aggregated IgG. In contrast, no response was obtained with RNA, DNA and aggregated IgG in patients with systemic lupus erythematosus (SLE) or in controls. In the RA and the SLE groups no significant correlation was found between the response of RNA, DNA and aggregated IgG and the serum titres of anti-DNA and antinuclear antibodies. No difference in basophil cell count in peripheral blood and basophil histamine content was found between RA, SLE and controls. Our results point to an involvement of an autoimmune type I reaction in the pathogenesis of RA directed against the nuclear components RNA and DNA and against immune complexes.
This study concerns observations on isolated rat mast cells sensitized to specific antigen. Specific binding of antigen to the surface immunoglobulins of these cells could be demonstrated by immunofluorescence technique as well as by radiolabelled antigen binding and the degree of binding parallelled the allergic reaction as judged by histamine release. Exposure of mast cells to antigen at both low and high antigen concentrations did not change the distribution of the surface immunoglobulins. Furthermore, neither capping not shedding could be induced, even by excessive antigen stimulation. The amount of antigen molecules bound to surface Ig was linearly correlated to the allergic histamine release. When mast cells were sensitized to two antigens of different molecular weight, the cells showed the highest sensitivity to the antigen having the highest molecular weight. These results indicate that both the amount of antigen and the molecular weight of the antigen bound to surface Ig are important factors in the allergic histamine release from mast cells, whereas surface Ig redistribution is not.
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.
Eleven thymectomized and ten non-thymectomized patients with myasthenia gravis, matched with respect to sex, age, duration and severity of the disease were investigated with respect to routine clinical features, electrophysiological examination, HLA-typing, auto-antibodies, lymphocyte subpopulations in peripheral blood, Concanavalin A-induced release of leucocyte migration inhibitory factor (LIF), in vitro lymphocyte activation by mitogens and antigens and response to primary immunization with dinitrochlorobenzene measured in vivo and in vitro. The following conclusions could be drawn. The immune response to external antigens seems to be normal in myasthenia gravis and thymectomy is not followed by general defects in immune competence; at least as investigated by current techniques. The only reduction of responsiveness demonstrable in the thymectomized group was a decreased release of LIF by Concanavalin A-stimulated lymphocytes. Primary immune responses appear to be increased after adult thymectomy, which may be due to a decrease in suppressor T-lymphocyte activity. A hypothesis is formulated that Concanavalin A-induced release of LIF may reflect the competence of suppressor T-lymphocytes in man.
Skin biopsies for immunofluorescent studies were taken from patients with contact dermatitis (positive patch tests), atopic dermatitis and allergic vasculitis for comparison with normal-appearing skin from the same patients, and from healthy controls. A variety of deposits of immunoglobulins, complement components and fibrinogen were demonstrated in 6 out of 20 patients with contact dermatitis, 7 out of 10 with atopic dermatitis, 8 out of 10 with allergic vasculitis, and in 4 out of 20 control individuals. No diagnostic pattern of deposits was found. Elevated serum IgE and eosinophilic counts were found in patients with atopic dermatitis, and high serum IgA and fibrinogen levels were found in the allergic vasculitis group.
A 73-year-old woman with rheumatoid arthritis was treated with Levamisole, 150 mg per day, on 2 days a week. Her arthritis improved, but she developed a severely itching rash, and the treatment was stopped after 6 months. Penicillamine was subsequently given and tolerated without skin complications. 15 months after regular Levamisole was stopped, she was given a single dose of 150 mg which provoked fever of 40 degrees C and rash. Thirteen punch-biopsy specimens were examined by direct immunofluorescence microscopy. During the Levamisole treatment, granular deposits of IgG and C3 were found at the dermal--epidermal junction. Subsequently, the deposits disappeared, but reappeared after Levamisole challenge. The patient's leukocytes were exposed in vitro to Levamisole, and 36% of the total histamine content in the basophils was released. Our results provide further evidence that Levamisole can cause type-I as well as type-III hypersensitivity.