Immunological functions of oxidized human immunoglobulin G in type 1~diabetes mellitus: Its potential role in diabetic smokers as a biomarker of elevated oxidative stress

Article type: Research Article

Authors: Rasheed, Zafar | Al-Shobaili, Hani A. | Alzolibani, Abdullateef A. | Ismail Khan, Muhammad | Tariq Ayub, Muhammad | Khan, Mohammed Imran | Rasheed, Naila

Affiliations: Department of Medical Biochemistry, College of Medicine, Qassim University, Buraidah, KSA | Department of Dermatology, College of Medicine, Qassim University, Buraidah, KSA | Department of Physiology, College of Medicine, Qassim University, Buraidah, KSA | Department of Biochemistry, College of Applied Medical Sciences, Qassim University, Buraidah, KSA | Institute of Genetics, School of Biology, Queens Medical Center, Medical School, Nottingham, UK

Note: [] Corresponding author: Dr. Zafar Rasheed, Department of Medical Biochemistry, College of Medicine, Qassim University, P.O. BOX 6655, Buraidah-51452, KSA. Tel.: +96 531269227; E-mail: [email protected]

Abstract: The role of oxidized immunoglobulin G in type 1 diabetic smokers has been investigated in the present study. Human immunoglobulin G (IgG) was modified by reactive oxygen species (ROS). The binding characteristics of circulating autoantibodies in type 1 diabetes patients against native and modified IgG were assessed by direct binding ELISA. High degree of specific binding by 68.5% of patients sera towards ROS-modified IgG was observed in comparison to its native analogue (p< 0.05). In addition, diabetic smokers (n=28) were examined and the results were compared with diabetic non-smokers (n=26). Circulating antibodies of diabetic smokers showed substantially stronger binding to modified IgG as compared with the antibodies present in diabetic non-smokers (p< 0.05). Normal human sera (n=53) showed negligible binding with either antigen. Competitive inhibition ELISA reiterates the direct binding results. The increase in total serum protein carbonyl levels in the diabetic smokers was largely due to an increase in oxidized IgG. Diabetic smokers showed substantially higher carbonyl contents in sera as well as in purified IgG as compared with sera and IgG of diabetic non-smokers. Collectively, the oxidation of plasma proteins, especially IgG, might enhance oxidative stress in type 1 diabetes smokers.

Keywords: Type 1 diabetic smokers, oxidized IgG, autoantibodies, reactive oxygen species

DOI: 10.3233/DMA-2011-0803

Journal: Disease Markers, vol. 31, no. 1, pp. 47-54, 2011