A C5a-Immunoglobulin complex in chronic lymphocytic leukemia patients is associated with decreased complement activity.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
25
07
2018
accepted:
27
11
2018
entrez:
3
1
2019
pubmed:
3
1
2019
medline:
24
9
2019
Statut:
epublish
Résumé
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. The therapeutic approach to CLL includes chemotherapeutic regimens and immunotherapy. Complement-mediated cytotoxicity, which is one of the mechanisms activated by the therapeutic monoclonal antibodies, depends on the availability and activity of the complement (C) system. The aim was to study the structure of circulating C components and evaluate the importance of C5 structural integrity for C activity in CLL patients. Blood samples were collected from 40 naïve CLL patients and 15 normal controls (NC). The Western blot analysis showed abnormal C5 pattern in some CLL patients, while patterns of C3 and C4 were similar in all subjects. Levels of the C activation markers sC5b-9 and C5a were quantified before and after activation via the classical (CP) and alternative (AP) pathways. In patients with abnormal C5, basal levels of sC5b-9 and C5a were increased while activities of the CP and of the CP C5-convertase, the immediate C5-upstream complex, were decreased compared to NC and to patients with normal C5. The data indicate a link between CP activation and apparent C5 alterations in CLL. This provides a potential prognostic tool that may personalize therapy by identifying a sub-group of CLL patients who display an abnormal C5 pattern, high basal levels of sC5b-9 and C5a, and impaired CP activity, and are likely to be less responsive to immunotherapy due to compromised CP activity.
Identifiants
pubmed: 30601845
doi: 10.1371/journal.pone.0209024
pii: PONE-D-18-22000
pmc: PMC6314568
doi:
Substances chimiques
Complement Membrane Attack Complex
0
SC5b-9 protein complex
0
Complement C5a
80295-54-1
Complement C3-C5 Convertases
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0209024Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Immunol Lett. 1989 Jul;22(1):1-6
pubmed: 2550362
Clin Chem. 1999 Aug;45(8 Pt 1):1190-9
pubmed: 10430784
Immunol Lett. 1987 Feb;14(3):255-9
pubmed: 3570363
Nat Med. 2003 Apr;9(4):431-8
pubmed: 12612546
Lancet Oncol. 2007 Apr;8(4):361-2
pubmed: 17395110
Clin Exp Immunol. 1995 Dec;102(3):575-81
pubmed: 8536375
Leukemia. 2015 Jan;29(1):107-14
pubmed: 24787488
J Immunol. 2014 Mar 15;192(6):2837-45
pubmed: 24554772
Mol Immunol. 1985 Feb;22(2):101-6
pubmed: 3156272
Nat Rev Immunol. 2010 May;10(5):317-27
pubmed: 20414205
J Biol Chem. 2016 Aug 5;291(32):16494-507
pubmed: 27252379
J Immunol. 2015 Jun 1;194(11):5488-96
pubmed: 25911760
Clin Exp Immunol. 1988 Sep;73(3):484-8
pubmed: 2463123
Clin Exp Immunol. 2014 Oct;178(1):142-53
pubmed: 24853370
Ann N Y Acad Sci. 2009 Sep;1173:865-73
pubmed: 19758239
Clin Exp Immunol. 1995 Jan;99(1):112-6
pubmed: 7813102
Nat Rev Clin Oncol. 2010 Sep;7(9):521-32
pubmed: 20603650
Leukemia. 1996 Sep;10(9):1509-13
pubmed: 8751471
Clin Exp Immunol. 1985 Jun;60(3):489-95
pubmed: 4017286
Mol Immunol. 2008 Oct;45(16):4073-9
pubmed: 18706699
Mol Immunol. 2015 Aug;66(2):164-70
pubmed: 25795308