Cell-free IgG-aggregates in plasma of patients with chronic lymphocytic leukemia cause chronic activation of the classical complement pathway

PloS One
Regina MichelisAndrei Braester

Abstract

Therapy regimens for Chronic lymphocytic leukemia (CLL) commonly include chemotherapy and immunotherapy, which act through complement-mediated-cytotoxicity (CDC) and other mechanisms. CDC depends on several factors, including the availability and activity of the complement classical pathway (CP). Recently, a significant decrease in CP activity was shown to be associated with an immunoglobulin-C5a complex (Ig-C5a) and other markers of chronic CP activation in 40% of the patients. The study focused on the involvement of IgG-hexamers, an established CP activator, in the mechanism of chronic CP activation in CLL. Sera from 51 naïve CLL patients and 20 normal controls were collected. CP and alternative pathway (AP) activities were followed by the complement activity marker sC5b-9. Serum high molecular weight (HMW) proteins were collected by gel-filtration chromatography and their complement activation capacity was assessed. The levels of IgM, another established CP activator, were measured. Data were associated with the presence of Ig-C5a. Baseline levels of activation markers negatively correlated with CP and the AP activities, supporting chronic complement activation. In patients with Ig-C5a, HMW proteins that are not IgM, activat...Continue Reading

References

Jun 16, 2005·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Regina MichelisBatya Kristal
Jul 7, 2010·Nature Reviews. Clinical Oncology·Constantine S Tam, Michael J Keating
Oct 30, 2010·Clinical Lymphoma, Myeloma & Leukemia·Susan O'Brien, Anders Osterborg
Jan 19, 2011·Haematologica·Kate HodgsonCarol Moreno
Mar 1, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Frank J BeurskensRonald P Taylor
Mar 15, 2014·Science·Christoph A DiebolderPaul W H I Parren
Jun 1, 1986·Immunology Today·A FeinsteinM I Taussig
Nov 5, 2014·Frontiers in Immunology·Gestur VidarssonTheo Rispens
Feb 24, 2015·Molecular Immunology·Joost P M MelisPaul W H I Parren
Apr 26, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sofia MortensenGregers R Andersen
Jan 20, 2017·Nature Reviews. Disease Primers·Thomas J KippsKanti Rai

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Methods Mentioned

BETA
ELISA
gel-filtration
gel filtration
affinity binding

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