Biomedical subjects

W Leitmann

Publications and source records attributed to W Leitmann.

3 recordsLinked to original sources

PubMed1990

Circulating immune complexes in HIV-infected persons.

Circulating immune complexes are part of normal immune defense mechanisms and, therefore, present in various infectious--bacterial and viral--diseases. On the other hand, they are obviously involved in pathogenic mechanisms, e.g., autoimmune diseases or different forms of malignancies. Both autoimmune and infectious features are recorded in the acquired immunodeficiency syndrome. Thus, elevated levels of antigen-antibody complexes in HIV-infected persons had to be expected, and they were in fact demonstrated by several authors. In a cohort study, it was additionally shown that circulating immune complexes are of prognostic relevance. After an introduction concerning the physiological and pathophysiological role of circulating immune complexes in general, their involvement in the course of HIV infections is presented and discussed. In addition, there is a critical review of the most commonly applied assay systems for the detection and quantification of circulating immune complexes.

Antigen-Antibody Complex↗

PubMed1989

Are retroviruses involved in the pathogenesis of SLE? Evidence demonstrated by molecular analysis of nucleic acids from SLE patients' plasma.

High molecular weight DNA of up to 20 kbp and, additionally, an RNase-insensitive RNA of more than 60 b were isolated from plasmapheresis fluids taken from patients with active systemic lupus erythematosus (SLE). Similar nucleic acids could not be demonstrated in the plasma samples from patients with Waldenstroem's disease, rheumatoid arthritis, myasthenia gravis, and other diseases including active systemic disorders. The purified nucleic acids were analyzed in several ways; they proved to be immunogenic by inducing polyclonal and monoclonal antibodies to natural DNA as well as to synthetic polynucleotides (e.g. polyguanylic acid) after injection into experimental animals (rabbits or mice respectively). Biochemical and molecular cloning analysis of the DNA revealed features like high levels of CpG-dinucleotides, usually not observed in common human DNA. A possible exogenous origin was substantiated by comparative sequence studies of cloned plasma DNA, which showed homologies to human retroviruses, e.g. PL1 (85%/60 b) and the sequences of the gag and pol genes of human immunodeficiency virus type I (85%/157 b). Experiments applying isolated plasma nucleic acids in transfection experiments showed the induction of morphological changes in an EBV-immortalized B-cell line drawn from a healthy human donor, such as vacuolization and syncitia formation. Northern blot analysis demonstrated, exclusively in the transfected cell line, the expression of mRNA homologous to the cloned plasma DNA. Using this clone as a probe, homologous sequences could be demonstrated by Northern blot analysis in EBV-immortalized cell lines from SLE patients only and, by means of DNA amplification, in peripheral blood lymphocytes from SLE and AIDS patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Antibody binding of macromolecular DNA and RNA in the plasma of SLE patients.

Plasmapheresis fluids from 20 patients with clinically active SLE, from three patients with Waldenstrom's disease, from three patients with rheumatoid arthritis, two patients with myasthenia gravis and other diseases including active systemic disorders were precipitated using polyethylene glycol 6000 (PEG). By applying ethidium bromide staining, plasma nucleic acids (PNA) could be demonstrated in PEG-precipitates of SLE patients exclusively. Purified immunoglobulins of SLE plasma precipitates were shown to form antigen-antibody complexes with PNA as demonstrated by electronmicroscopy. Further characterization of PNA by agarose gel electrophoresis revealed a molecular weight up to 20 kbp. Cesium chloride buoyant density gradients showed non-homogeneous molecules, excluding pure microbial origin. In spite of RNase digestion, the PNA contained RNA with 30-70% riboguanosine as shown by nucleoside analysis. The high amount of guanosine-rich RNA was further supported by similarities between PNA and polyriboguanylic acid in hyperchrome shifting due to thermic denaturation. HPLC analysis showed a molecular weight of ribonucleic acids of more than 60 b thus excluding mere oligonucleotides. In contrast to B-type dsDNA, PNA from SLE patients were immunogenic. Antibodies against PNA could be induced in rabbits by subcutaneous injection. The antisera thus obtained showed crossreactivity with polyriboguanylic acid and dsDNA preparations.

Antibodies, Antinuclear↗