Biomedical subjects
T E Feltkamp
Publications and source records attributed to T E Feltkamp.
Wheat grains: a substrate for the determination of gluten antibodies in serum of gluten-sensitive patients.
A simple method of detecting gluten antibodies in serum is described. Cryostat sections of wheat grains proved to be an excellent substrate in the immunofluorescence technique. Rabbit antisera to gliadin and alpha-gliadin, and high percentage of sera from patients with gluten-induced enteropathy had antibodies that reacted with an internal structure of wheat grains. These antibodies could be absorbed with gliadin and with alpha-gliadin.
Segregation of HLA haplotypes in 100 families with a myasthenia gravis patient.
An analysis of the HLA data of 100 myasthenia gravis (MG) patients and their first degree relatives and spouses is presented. The family studies confirmed the excess of B8 in the myasthenia gravis patients and showed that the excess was not limited to the A1, B8 haplotype. An excess of B8 homozygous patients was found from the matings of two B8 heterozygous parents, suggesting the existence of a dominant B8 linked MG susceptibility. B8 homozygous individuals run a 4-7 times higher risk of acquiring myasthenia gravis than B8 heterozygous individuals.
Immunology of DNA. I. The influence of reaction conditions on the Farr assay as used for the detection of anti-ds DNA.
The sensitivity and the specificity of the Farr assay for the detection of antibodies to double stranded (ds) DNA depends very much on the reaction conditions. The interaction between ds DNA and anti-ds DNA is inhibited when ionic strength and pH are increased. ds DNA is bound by normal sera at ionic strength lower than 0.11 M NaCl and at physiological ionic strength when the pH is lower than 7.2. Substantial binding of DNA by normal serum takes place in barbitone, borate or Tris-HCl buffers at concentrations of 30 mM or higher, even at a pH higher than 7.2. Such binding is due to Clq and is only partially prevented by heating the serum for 30 min at 56 degrees C, but 10 mM phosphate in the incubation mixture completely prevents it. Standardization of ionic strength, pH, phosphate concentration, incubation volume and DNA-serum ratio enhances the diagnostic usefulness of the Farr assay.
Immunology of DNA. II. The effect of size and structure of the antigen on the Farr assay.
The Farr assay for the detecton of antibodies to double stranded (ds) DNA is influenced by the DNA preparations used as antigen. To elucidate this the molecular weight of the antigen preparation, contamination with proteins and presence or absence of single stranded (ss) regions were studied with the following conclusions: 1) The degree of DNA binding by antibodies is linearly dependent on the molecular weight of the DNA, provided that this does not exceed 10 X 10(6). 2) Deproteinization of E. coli DNA by chromatography on methylated albumin-kieselguhr(MAK) columns results in lower binding by most sera. 3) ds DNA preparations sometimes contain ss regions which bind antibodies to ss DNA. The difference in behaviour of different ds DNA preparations may be ascribed entirely to these factors and not to differences in antigenic determinants. We have standardized the Farr assay and enhanced its specificity by the use of circular DNA isolated from bacteriophage PM2.
HL-A antigens, autoantibody production, and associated diseases in thymoma patients, with and without myasthenia gravis.
The sera of 67 patients with thymomas-43 with myasthenia gravis (thymoma(+) MG(+)) and 24 without myasthenia gravis (thymoma (+) MG (-)) from 5 Dutch centers were examined with the indirect immunofluorescence test for the presence of antibodies reacting with skeletal muscle (AMA), thyroid tissue, gastric parietal cells, adrenocortex and antinuclear antibodies (ANA). The data were compared with those obtained in a group 83 MG patients in whom a thymoma was excluded by histological verification (thymoma (-) MG (+)) and with 1106 controls from the normal population. Histocompatibility (HL-A) antigens were tested in 24 thymoma (+) MG (+), 23 thymoma (+) MG (-), and 43 thymoma (-) MG (+) patients and 533 controls from the Dutch population. AMA was found in all thymoma (+) MG (+) cases, in 42% of thymoma (+) MG (-), in 11% of thymoma (-) MG (+), and in less than 1% of the controls. The differences between each of these groups are significant (p less than 0.01, Table 3.) ANA was found in 54%, 50%, 18%, and 4%, respectively, of the above mentioned groups. The differences between the thymoma (+) and the thymoma (-) groups are significant (p less than 0.001. Table 4). The frequencies of antibodies reacting with thyroid tissue, gastric parietal cells and adrenocortex were low and showed no differences between the groups. The frequencies of HL-A8 were significantly decreased in both thymoma groups that had a relatively high incidence of associated immunological disorders (Table 5). Patients with MG and without antimuscle antibodies have no thymomas: This rule is of practical value in the management of the MG patient.
Lactate dehydrogenase (LDH)-IgG3 immunoglobulin complexes in human serum.
Sera of fifteen patients containing complexes of LDH and IgG were analysed. The LDH-IgG complexes of fourteen of these patients were investigated for their subclass specificity. They appeared to consist of LDH and IgG3, except for one of the patients. The serum of the latter patient also contained complexes of LDH and IgG1. In this serum both types of the immunoglobulin light chains were involved in the formation of the complexes, whereas in the serum of the patients with LDH-IgG3 complexes alone, they only contained one of the two immunoglobulin light chain types; it mainly concerned kappa type. The results of the present study were compared to those of a previous study on LDH-IgA complexes, in which the IgA fraction always contained light chains of kappa type. The mean LDH activity and the heat stability of the LDH activity in the sera with LDH-IgA complexes appeared to be higher than in the sera with LDH-IgG3 complexes. In contrast to complexes of LDH and IgA which occurred in all age groups LDH-IgG3 complexes were mainly found in elderly persons. Although auto-antibodies to different tissue antigens were present in the majority of the sera containing LDH IgG3 complexes, antibodies to LDH could not be demonstrated. A relationship between the presence of the complexes in the serum and a particular disease could not be established.
Immunology of DNA. III. Crithidia luciliae, a simple substrate for the determination of anti-dsDNA with the immunofluorescence technique.
C. luciliae are hemoflagellates nonpathogenic for man and easy to culture. They have a giant mitochondrion, in which the mitochondrial DNA is concentrated in a single large network, the kinetoplast. When used as a substrate for the indirect immunofluorescence technique, studying sera from patients with SLE, we could demonstrate a very good correlation between this test and the Farr assay for the demonstration of antibodies to double-stranded DNA. Although the sensitivity of both techniques is on the same order of magnitude, the IF technique has the following advantages over the Farr assay. It is easy to perform in laboratories equipped for autoimmune serology. It possesses an intrinsic check on the immunoglobulin character of the DNA-binding activity. It allows one to determine the Ig classes and subclasses of antibodies to DNA. It permits study of complement fixation to antibodies without interference of Clq fixation to DNA or anticomplementarity of the serum. There is an absence of interference with antibodies to single-stranded DNA.
LDH-IgA immunoglobulin complexes in human serum.
Human sera containing complexes of lactatedehydrogenase (LDH) and immunoglobulin A (IgA) were studied. Such complexes could be demonstrated in a number of sera with abnormalities in electrophoretic pattern of the LDH isoenzymes. LDH-IgA complexes were observed in a number of sera in which the LDH-2 band was missing, in a serum with all LDH activity in the betta-gamma-globulin region, but also in some sera with only minor abnormalities in the LDH isoenzyme pattern. It is shown that the IgA bound to LDH is of the kappa light chain type. Auto-bodies were not detected in the sera. Therefore, the formation of the LDH-IgA complexes does not seem to be the result of an antigen-antibody reaction.
The preparation of astatine labelled proteins.
Explore the source record for details and available documents.
Detection of antibodies to DNA by radioimmunoassay and immunofluorescence.
Explore the source record for details and available documents.
Antinuclear antibodies.
Explore the source record for details and available documents.
Hypothyroidism after thyroidectomy for Graves's disease: a search for an explanation.
Out of 38 patients who had undergone subtotal thyroidectomy for Graves's disease seven to 20 years previously 15 developed hypothyroidism. In these 15 patients autoantibodies against thyroid cytoplasm were significantly more frequent than in the 23 euthyroid patients, though there was no difference in the prevalence of autoantibodies against thyroglobulin. Histological examination of the thyroid tissue removed at operation showed that significantly more plasma cells and lymphoid follicles with germinal centres were present in patients who subsequently developed hypothyroidism than in those who remained euthyroid. No differences in the amount of lymphocytic infiltration were seen in hypothyroid and euthyroid patients.The results suggest that B lymphocytes play a part in the development of postoperative hypothyroidism in Graves's disease. It is proposed that Graves's disease and Hashimoto's disease are different aspects of the same basic autoimmune process.
[HL-A typing and autoantibodies in patients with myasthenia gravis].
Explore the source record for details and available documents.
[Systemic lupus erythematosus (SLE). I. New insights into serology and pathogenesis].
Explore the source record for details and available documents.
[Systemic lupus erythematosus (SLE). II. New insights into its etiology].
Explore the source record for details and available documents.
Myasthenia gravis, autoantibodies, and HL-A antigens.
The serum of 100 patients with myasthenia gravis and 441 of their first-degree relatives was studied for the presence of autoantibodies against several antigens. Antibodies to skeletal muscle were present in 22% of the patients and in 2% of the relatives. Both these frequencies were significantly higher than those in matched control subjects. Also, antinuclear antibodies were present more often both in the patients and in the relatives. Typing for HL-A antigens had shown a positive correlation between HL-A 8 and myasthenia gravis which was significantly higher in women than in men. Antibodies to skeletal muscle and thymomas were found to be much rarer in HL-A 8-positive patients than in HL-A 8-negative patients; HL-A 8-positive patients acquired the disease at an earlier age.HL-A 2-positive patients more often had thymomas and antibodies to skeletal muscle than HL-A 2-negative patients; HL-A 2-positive patients acquired myasthenia gravis at a later age.The fact that the clinical aspects of the HL-A 8-negative and HL-A 2-positive patients were different from those of the HL-A 8-positive and HL-A 2-negative patients justifies the hypothesis that there are two forms of myasthenia gravis.
Immunofluorescence microphotometry for the detection of platelet antibodies. I. Standardization of the method.
Explore the source record for details and available documents.