{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:52:07Z","timestamp":1780638727152,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR2969"],"award-info":[{"award-number":["FOR2969"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:p>Light chain amyloidosis (AL) is one of the most common forms of systemic amyloidosis and is caused by the deposition of insoluble fibrils derived from misfolded and aggregated immunoglobulin light chains (LC). To uncover the causes leading to this aggregation, we compared AL LC sequences with those of patients with the related disease multiple myeloma (MM), which do not aggregate in insoluble fibrils <jats:italic>in\u2009vivo<\/jats:italic>. IGLV2\u201014 is one of the most common AL\u2010associated IGLV subfamilies. Here, we analysed IGLV2\u201014 LC sequences of 13 AL and eight MM patients in detail. We found that AL\u2010associated LCs presented a lower median mutation count (7.0 vs. 11.5 in MM; <jats:italic>P<\/jats:italic>\u2009=\u20090.045), as well as an overall composition of less charged amino acids than MM LCs. However, we did not find a mutation that was present in \u2265\u200950% of the AL and not in the MM sequences. Furthermore, we did not find a significant difference in the isoelectric point (pI) in general, suggesting similar stability of the LCs in AL and MM. However, the subgroup of patients without a detectable heavy chain stood out. Surprisingly, they are characterized by an increase in mutation count (median 7.0 vs. 5.5) and pI (median 7.82 vs. 6.44, <jats:italic>P<\/jats:italic>\u2009=\u20090.043). In conclusion, our data suggest that the amount of mutations and the introduction of charges play a crucial role in AL fibril formation, as well as the absence or presence of a potential heavy chain binding partner.<\/jats:p>","DOI":"10.1111\/febs.16805","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T15:33:55Z","timestamp":1682436835000},"page":"4256-4267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparison of <scp>IGLV2<\/scp>\u201014 light chain sequences of patients with <scp>AL<\/scp> amyloidosis or multiple myeloma"],"prefix":"10.1111","volume":"290","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5791-698X","authenticated-orcid":false,"given":"Natalie","family":"Berghaus","sequence":"first","affiliation":[{"name":"Medical Department V, Amyloidosis Center Heidelberg University Hospital  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Schreiner","sequence":"additional","affiliation":[{"name":"Medical Department V, Amyloidosis Center Heidelberg University Hospital  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra M.","family":"Poos","sequence":"additional","affiliation":[{"name":"Medical Department V, Section of Multiple Myeloma Heidelberg University Hospital  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Raab","sequence":"additional","affiliation":[{"name":"Medical Department V, Section of Multiple Myeloma Heidelberg University Hospital  Germany"},{"name":"National Centre for Tumor Diseases (NCT)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Medical Department V, Section of Multiple Myeloma Heidelberg University Hospital  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