Goodpasture disease fulfils all criteria for a classical autoimmune disease, where autoantibodies targeted against the non-collagenous domain of the ␣3-chain of collagen IV initiates an inflammatory destruction of the basement membrane in kidney glomeruli and lung alveoli. This leads to a rapidly progressive glomerulonephritis and severe pulmonary hemorrhage. Previous studies have indicated a limited epitope for the toxic antibodies in the N-terminal part of the non-collagenous domain. The epitope has been partially characterized by recreating the epitope in the non-reactive ␣1-chain by exchanging nine residues to the corresponding ones of ␣3. In this study we have investigated to what extent each of these amino acids contribute to the antibody binding in different patient sera. The results show that seven of the nine substitutions are enough to get an epitope that is recognized equally well as the native ␣3-chain by all sera from 20 clinically verified Goodpasture patients. Furthermore, the patient sera reactivity against the different recombinant chains used in the study are very similar, with some minor exceptions, strongly supporting a highly defined and restricted epitope. We are convinced that the restriction of the epitope is of significant importance for the understanding of the etiology of the disease. Thereby also making every step on the way to characterization of the epitope a crucial step on the way to specific therapy for the disease.Goodpasture disease is known and characterized as a classic autoimmune disease. The disease is B cell and antibody mediated, with autoantibodies directed against proteins in the glomerular basement membrane and lung alveoli. When bound to self-structures in the kidney and lung, the antibodies initiate an inflammatory destruction of tissue by recruitment of complement leading to rapidly progressive glomerulonephritis often accompanied with severe and life threatening lung hemorrhage. The major self-epitope is located on the ␣3-NC1 domain of collagen IV. Collagen IV ␣3-chain has a limited distribution in the body and is only found in a few specialized basement membranes including the glomerular and alveolar basement membranes, thus explaining the specific organ involvement in Goodpasture disease. Goodpasture disease is indeed an antibody mediated disease as proven by the transfer of disease to monkeys by injection of kidney bound antibodies from Goodpasture patients (1) and the therapeutic effect of treating patients with plasma exchange and immunosuppressive drugs to reduce the amount of circulating antibodies (2). The Goodpasture epitope is a conformational epitope, which is indicated by the loss of reactivity to autoantibodies when the tertiary protein structure is disrupted by reduction of disulfide bonds (3). The epitope is also known as a cryptotope, i.e. the epitope is hidden in the native protein structure and is fully exposed first when the protein is partially denatured (4).Trying to map an epitope for a specific autoimmune disorder is very difficult, since in ...
In the Nordic countries a receiver height of 2 m has often been used when calculating noise levels over large areas for socioacoustic surveys, but within the EU 4 m is used. Here results are presented for railway noise calculations at both heights in 1459 points across several areas in Sweden. The average difference in equivalent level is 2.5 dB higher at 4 m height than at 2 m, which in turn leads to 10 % -40 % less predicted annoyance if the exposure is calculated at 4 m.
This study is part of the Swedish research program TVANE, where a number of questionnaire surveys has been performed. A comparison between three areas demonstrate that the reported annoyance is higher where the traffic intensity is higher even if the equivalent noise level is the same. The traffic intensity varies with a factor of 7 between the areas, and the reported annoyance is increased 1.3-2.5 times.
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