Identification and characterization of antibodies elicited by human cystatin C fragment

Izabela Behrendt , Martyna Prądzińska , Marta Spodzieja , Paulina Czaplewska , Aleksandra Kołodziejczyk , Aneta Szymańska , Franciszek Kasprzykowski , Susanna L. Lundström , Roman A. Zubarev , Sylwia Rodziewicz-Motowidło

Abstract

Amyloid formation is associated with a number of neurodegenerative diseases that affect the independence and quality of life of aging populations. One of rather atypical, occurring at a young age amyloidosis is hereditary cystatin C amyloid angiopathy (HCCAA) related to aggregation of L68Q variant of human cystatin C (hCC). Human cystatin C plays a very important role in many aspects of human health; however, its amyloidogenic propertiesmanifested inHCCAA present a real, lethal threat to some populations and any work on factors that can affect possible influencing hCC aggregation is not to overestimate. It was proved that interaction of hCC withmonoclonal antibodies suppresses significantly hCC dimerization process. Therefore, immunotherapy seems to be the right approach toward possible HCCAA treatment. In this work, the hCC fragment encompassing residue 60‐70 (in 2 variants: linear peptide and multiple antigenic peptide) was used as an immunogen in rabbit immunization. As a result, specific anti‐hCC antibodies were found in both rabbit sera. Surprisingly, rabbit antibodies were obtained after immunization with only a short peptide. The obtained antibodies were characterized, and their influence on the aggregation propensity of the hCC molecules was evaluated. The antibodies turned out not to have any significant influence on the cystatin C dimerization process.Nevertheless,we hope that antibodies elicited in rabbits by other hCC fragments could lead to elaboration of effective treatment against HCCAA.
Author Izabela Behrendt (FCh / DBCh / LMCh)
Izabela Behrendt,,
- Laboratory of Medical Chemistry
, Martyna Prądzińska (FCh / DBCh / LMCh)
Martyna Prądzińska,,
- Laboratory of Medical Chemistry
, Marta Spodzieja (FCh / DBCh / LMCh)
Marta Spodzieja,,
- Laboratory of Medical Chemistry
, Paulina Czaplewska (IFB / M020 / DMCB)
Paulina Czaplewska,,
- Department of Molecular and Cellular Biology
, Aleksandra Kołodziejczyk (FCh / DBCh / LMCh)
Aleksandra Kołodziejczyk,,
- Laboratory of Medical Chemistry
, Aneta Szymańska (FCh / DBCh / LMCh)
Aneta Szymańska,,
- Laboratory of Medical Chemistry
, Franciszek Kasprzykowski (FCh / DBCh / LMCh)
Franciszek Kasprzykowski,,
- Laboratory of Medical Chemistry
, Susanna L. Lundström
Susanna L. Lundström,,
-
, Roman A. Zubarev
Roman A. Zubarev,,
-
, Sylwia Rodziewicz-Motowidło (FCh / DBCh / LMCh)
Sylwia Rodziewicz-Motowidło,,
- Laboratory of Medical Chemistry
Journal seriesJournal of Molecular Recognition, ISSN 0952-3499, (A 25 pkt)
Issue year2018
Vol31
No4
Pages1-13
Publication size in sheets0.6
Keywords in Englishepitope identification, human cystatin C, mass spectrometry, multiple antigenic peptide, polyclonal antibodies
DOIDOI:10.1002/jmr.2689
URL http://onlinelibrary.wiley.com/doi/10.1002/jmr.2689/epdf
Languageen angielski
Score (nominal)25
ScoreMinisterial score = 25.0, 20-06-2018, ArticleFromJournal
Ministerial score (2013-2016) = 25.0, 20-06-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 2.175 (2) - 2016=2.051 (5)
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