FOR 2969: Mechanisms of antibody light chain misfolding in systemic AL amyloidosis

轻链或AL淀粉样变性是德国最常见的系统性淀粉样变性类型之一。晚期肾脏或心脏受累可导致快速透析或死亡。这种疾病是由抗体轻链的错误折叠和聚集引起的，这些抗体轻链是在单克隆B-call病症的过程中产生的。AL淀粉样变性的一个特别显著的特征是其临床表现的多变性。这种异质性可能是由轻链和多态性聚集体结构的天然多样性引起的。然而，确切的关系到目前为止还不清楚。该研究单位的目的是澄清两种特别突出的临床形式的AL淀粉样变性（占主导地位的心脏或肾脏受累）如何从蛋白质生化特性引起疾病和临床表现。我们将特别研究一级结构、蛋白水解加工、折叠和多态聚集体结构。广泛的方法学范围支持我们的研究策略，主要是为了提高基本的理解，但也可能为患者创造直接的利益，例如在早期诊断中。

The light chain or AL amyloidosis is one of the most abundant types of systemic amyloidosis in Germany. Advanced kidney or heart involvement can lead to rapid dialysis or death. The disease is caused by the misfolding and aggregation of antibody light chains, which are produced in the course of a monoclonal B-call disorder. A particular remarkable feature of AL amyloidosis is thevariability of its clinical manifestations. This heterogeneity is probably caused by the natural diversity of light chains and of the polymorphic aggregate structure. However, the exact relationships are not so far understood. This research unit aims to clarify for two specifically prominent clinical forms of AL amyloidosis (dominant heart or kidney involvement) how disease and clinical manifestations arise from protein biochemical properties. We will investigate in particular the primary structure, the proteolytic processing, the folding and the polymorphic aggregate structure. A broad methodological spectrum supports our research strategy which primarily seeks to improve the basic understanding but which may also create direct benefit for patients, for example in the early diagnosis.