Antibodies against 4-hydroxy-2-nonenal modified epitopes
recognized chromatin and its oxidized forms: Role of chromatin, oxidized forms
of chromatin and 4-hydroxy-2-nonenal modified epitopes in the etiopathogenesis
of SLE
Affiliations: Department of Dermatology, College of Medicine, Qassim
University, Buraidah, KSA | Department of Medical Biochemistry, College of
Medicine, Qassim University, Buraidah, KSA
Note: [] Corresponding author: Zafar Rasheed, Department of Medical
Biochemistry, College of Medicine, Qassim University, P.O. Box 6655,
Buraidah-51452, KSA. Tel.: +966 531269227; E-mail:
zafarrasheed@rocketmail.com
Abstract: Objectives: This study was undertaken to investigate the role of
lipid oxidative-by-product 4-hydroxy-2-nonenal (HNE)-modified human serum
albumin (HSA), chromatin, reactive oxygen species (ROS)-modified chromatin and
nitric oxide (NO)-modified chromatin in systemic lupus erythematosus (SLE). Methods: HSA was modified by HNE. Immunogenicity of modified HSA was
probed by inducing polyclonal antibodies in rabbits. Chromatin was isolated
from goat liver and modified by ROS or NO. Immunocross-reactions of Protein-A
purified anti-HNE-HSA-IgG with chromatin, ROS-chromatin and NO-chromatin were
determined. Autoantibodies from 74 SLE patients were screened. HSA was isolated
from SLE patients (SLE-HSA) and immunocross-reactions of isolated SLE-HSA with
HNE-specific antibodies were investigated. Results: HNE-HSA was found to be highly immunogenic in rabbits. The
notable feature of anti-HNE-HSA-IgG showed cross-reactions with chromatin,
ROS-chromatin and NO-chromatin (p< 0.01). High degree of specific binding to
HNE-HSA, chromatin, ROS-chromatin or NO-chromatin was observed with antibodies
from 55% of SLE patients. SLE anti-native/ oxidized chromatin antibodies showed
specificity towards HNE-HSA. Furthermore, SLE-HSA showed binding with
HNE-specific antibodies. Conclusions: This is the first study to demonstrate that chromatin
and its oxidized forms have been recognized by antibodies against HNE modified
epitopes. Our results provide an important insight into the immunological basis
of the reported HNE-modified epitopes in SLE.
