Biomedical subjects

F Heidenreich

Publications and source records attributed to F Heidenreich.

42 records · Page 3Linked to original sources

PubMed1988

Anti-acetylcholine receptor antibody specificities in serum and in thymic cell culture supernatants from myasthenia gravis patients.

We investigated the role of the thymus in myasthenia gravis by comparing the antigenic specificities of anti-acetylcholine receptor antibodies (anti-AChR), defined by competition with mouse monoclonal antibodies that bind to five different regions on human muscle AChR, in thymic culture supernatants and in serum pre- and post-thymectomy. Anti-AChR specificities present in the serum were broadly unchanged in 16 non-thymoma and six thymoma patients 7-30 months after thymectomy compared with an initial sample, although total anti-AChR frequently fell. The fine specificities of the anti-AChR synthesized in vitro by cultured lymphocytes from the thymus of ten patients (without thymoma) correlated significantly with that of the anti-AChR in the serum at the same time. We conclude that AChR-specific B cells in the thymus are representative of the total AChR-specific repertoire, and that thymectomy does not selectively deplete particular B cell clones.

Adolescent↗

PubMed1988

Epitopes on human acetylcholine receptor defined by monoclonal antibodies and myasthenia gravis sera.

The mouse monoclonal antibody (m.ab) binding sites on human acetylcholine receptor have been mapped by inhibition by F(ab')2 m.ab fragments, by competition with a rat m.ab against the main immunogenic region (anti-m.i.r), and by their ability to protect the a-Bungarotoxin (a-BuTx) binding sites from inhibition by a myasthenia gravis (MG) plasma. Two m.abs (C3 and D6) that bind to two distinct but overlapping regions on the AChR, were inhibited by the anti-m.i.r. m.ab M35. M.abs binding to three other regions protected the a-BuTx sites by up to 50%. In further inhibition assays these m.abs were used to define the binding sites for MG anti-AChR antibodies. There was considerable heterogeneity in the antigenic specificity of the MG sera. The inhibition of MG anti-AChR by anti-m.i.r. M35 correlated highly with inhibition by mouse m.ab D6, but not with inhibition by m.ab C3. There was a correlation between inhibition by m.abs F8 and B3, although these m.abs bind to two non-overlapping regions. Some MG anti-AChR antibodies bound to epitopes that only partially overlapped those defined by m.abs. Inhibition of human antibody binding by m.abs raised against specific antigens is a useful approach that should help define the epitopes to which autoantibodies bind.

Antibodies, Monoclonal↗

PubMed1988

Differences in fine specificity of anti-acetylcholine receptor antibodies between subgroups of spontaneous myasthenia gravis of recent onset, and of penicillamine induced myasthenia.

The antigenic specificity of anti-acetylcholine receptor antibodies (anti-AChR) from 70 recent onset myasthenia gravis (MG) and nine penicillamine MG patients was determined by inhibition experiments using monoclonal antibodies (m.abs) raised against human AChR. Differences were found between individuals and between the three clinical subgroups of idiopathic MG distinguished by age of onset, thymic pathology and HLA associations. Penicillamine-induced MG anti-AChR differed from that in age-matched MG controls but was similar to that in young-onset cases. The variable and heterogeneous antigenic specificity in MG suggests that AChR itself rather than a cross-reacting epitope is the primary antigen. Differences in specificity between MG subgroups may reflect a diversity of triggering factors or of immunoglobulin genes.

Adolescent↗

PubMed1988

Monoclonal anti-acetylcholine receptor antibodies as probes for human acetylcholine-receptor in myasthenia gravis.

Monoclonal antibodies have been shown to bind to five regions on human acetylcholine receptor, each probably consisting of a discrete epitope on the extracellular surface. Two of these regions are equivalent to the 'main immunogenic region', and the other three appear to be close to the a-Bungarotoxin binding sites. These antibodies have been used to probe differences in myasthenia gravis anti-acetylcholine receptor antibodies, to locate acetylcholine receptor in thymic tissue, and to look for naturally-occurring anti-idiotype antibodies. Anti-acetylcholine receptor antibody specificities differ between groups of patients defined by their age of onset, thymic pathology and HLA associations. Anti-AChR synthesised by the thymus in young onset patients has similar specificity to that found in the individual's serum, and may be stimulated by the presence of AChR on thymic myoid cells. However, myoid cells (defined by staining with anti-troponin and anti-myosin antibodies) do not appear to differ between control and myasthenia gravis patients and show no obvious involvement in an immunological reaction. There was no convincing evidence for the presence of anti-idiotype antibodies in myasthenia gravis patients.

Adult↗

PubMed1987

Antibody heterogeneity and specificity in myasthenia gravis.

Anti-AChR is heterogeneous within individuals and between individuals. Anti-AChR idiotypes are not shared to any large extent. Ten monoclonal antibodies raised against human AChR: (a) bind to five partially overlapping regions; (b) are not idiotypically identical even within a region; (c) do not all bind to the main immunogenic region; (d) four distinguish between normal and denervated human AChR; (e) can be used to define the antigenic determinants in MG. Antigenic specificities vary in different clinical groups. Antigenic specificities can change during the course of the disease, but some remain relatively constant. Thymus cultures make antibodies with the same specificity as those present in the serum of the individual. All monoclonal antibodies bind to myoid cells of normal and MG thymus. We find no convincing evidence of naturally occurring antiidiotype antibodies in MG sera.

Antibodies, Monoclonal↗

PubMed1985

Candida albicans and Candida stellatoidea, in contrast to other Candida species, bind iC3b and C3d but not C3b.

It was demonstrated that complement-coated sheep erythrocytes bind to Candida albicans cells grown in serum-free RPMI 1640 medium. Testing of purified complement components proved that iC3b and C3d were responsible for the reaction, whereas C3b and C3b-H reacted only slightly if at all. Binding occurred only to C. albicans and C. stellatoidea, not to other species pathogenic to humans. There was evidence of a lectinlike nature of the effect.

Animals↗