[Abnormal HLA-DR antigen expression in monocytes of patients with systemic lupus erythematosus and psoriasis vulgaris].
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Biomedical subjects
Publications and source records attributed to H Barthelmes.
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From the immune status in patients with tonsillitis it can be deduced that only a few indications on systemic immunodeficiencies can be found. Heterophilic tissue antibodies, antinuclear antibodies and circulating immune complexes indicate autoimmune processes. The results obtained are discussed from a clinical aspect.
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The antibodies of 50 old people of the age over 70 years were determined against ds-DNA and denaturized ds-DNA by the immune-fluorescence method, and it can be stated that denaturized ds-DNA antibodies are traceable in 16% of these sera. Such antibodies could not be found in control tests of seras of young people. However, the old people did not show may clinical symptom typical of the disease caused by these antibodies. In particular, there were no indications of an auto-immune disease, for that reason, these antibodies are to be considered as optional pathological ones.
Seven laboratories made a chessboard titration with a serum containing antimitochondrial antibodies and two conjugates labeled with fluorescein isothiocyanate. The variation of the plateau titer and the titer of the serum as well as the plateau-end point was slight with the exception of one case. The standardization of indirect immunofluorescence needs a close contact between the laboratories, the availability of reference sera and conjugates, and similar microscopic equipment.
After the intraperitoneal application of 3H-proline a higher grain density over the myocardium and the aorta in comparison with the cartilage, the glomeruli and the cutaneous connective tissue of rats was found. The maximal incorporation was established in the aorta at 6 h, in the skeletal muscle at 18 h after the injection of radioactive proline. Immunhistochemical findings reported in the literature and first results of our own indicate a special distribution pattern of the various collagen types in the organs under study. Seen in this connection the autoradiographic results may imply that type I and III collagen has a higher metabolic intensity than type II and IV collagen. Animals with renal hypertension of 3 weeks duration show an increase in the ratio of the extranuclear to the intranuclear grain density in the myocardium and the aorta after 3H-proline application.
Antibodies to N6-methyladenosine were produced in rabbit by means of immunization with N6-methyladenosine coupled to bovine serum albumin via periodate oxidation. Cross-reacting antibodies were removed by bovine serum albumin-Sepharose and appropriate nucleoside-human serum albumin absorbents. Nucleoside-specific antibodies were isolated by affinity chromatography of N6-methyladenosine-human serum albumin-Sepharose. The specificity of the purified antibodies has been demonstrated by complement fixation inhibition analyses using nucleoside analogues as inhibition than dAMP. Anti-N6-methyladenosine was used to detect N6-methyladenine in denatured DNAs from various sources by complement fixation. Practically no complement fixation has been found with DNAs containing no N6-methyladenine, such as calf thymus, salmon sperm, Micrococcus radiodurans, Streptomyces chrysomallus and Streptomyces hygroscopicus, whereas a weak reactivity occurred in the case of Bacillus subtilis DNA and Sarcina maxima DNA. For DNA from Proteus mirabilis, Escherichia coli K-12, E. coli B, E. coli WF+, lambda, T2 phages quantitative differences in the immunochemical reactivity were observed, which only partially correlate with the N6-methyladenine content of the DNAs. Other factors, influencing the accessibility of N6-methyladenine to the antibody-combining site have to be taken into consideration.
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Oligodeoxyribonucleotides act as inhibitors of the complement fixation caused by complexes between antibodies to defined oligodeoxyribonucleotides and denatured DNA. At concentrations higher than 50 micrograms oligodeoxyribonucleotide/ml complement fixation occurred in the absence of antigen. The extent of complement binding depends on the specificity of the antibodies as well as on the composition of the oligodeoxyribonucleotides. Complement fixation is observed most strongly with antisera to oligodeoxyribonucleotides and to denatured DNA, which belong predominantly to the IgM class. With two LE-sera, containing antibodies to denatured and to native DNA, no complement fixation was found. It is supposed that specific interactions of the oligodeoxyribonucleotides with amino acid residues closely neighbored to the antibody combining site lead to conformational changes in the antibody molecules and to an activation of the complement binding site.
The pathogenesis of the lupus erythematosus results from co-operation of three principles: (1) genetical disposition, (2) increased reactivity of the immune system, (3) different exogenic influences. The genetical disposition is confirmed by family investigations, metabolic disorders and immune anomalies as well as by parallels to animal models. The reaction manner of the immune system is genetically determined. Exogenic factors influence the immune system (behaviour) either as starter or by modifying the genetical material. The most striking humoral immune phenomenon is an immense number of (auto-)antibodies. Investigations of xeroderma pigmentosum as well as with DNA of different antigenity have shown that an increase of the antigenicity is unlikely for this phenomenon. In the serum of patients there were established and partially characterized factors (mitogens, granulocytic adherence-factor) for increasing the immune reactivity. The increase of such factors may be the sequence of a T-suppressor cell-defect. Like-wise no interdigitating cells in systemic lupus erythematosus have been found, cells which may be responsible for the terminal differentiation of T-lymphocytes. The mode of action of exogenic factors is represented and discussed with the example of the UV provocation.
Antibodies to the oligodeoxyribonucleotides d(pT)3, d(pT)4, d(pT)6 and d(pA-A-T-T) were elicited in rabbits by immunization with electrostatic complexes of the respective haptens with methylated bovine serum albumin (MBSA). The antisera were assayed by complement fixation using denatured DNA's of various sources as antigens. The specificities of the antibodies were determined by estimating the inhibition of the complement fixation reaction by defined oligodeoxyribonucleotides. The antibodies were shown to be specific for the sequence of the oligode-oxyribonucleotides or parts of it.
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