Preferential Recognition of Hydroxyl Radical-Modified Superoxide Dismutase by Circulating Autoantibodies in Patients with Alopecia Areata
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Alopecia areata (AA) is a common form oflocalized, non-scarring hair loss. The cause of AA isunknown but reports suggest an autoimmune etiology,where oxygen free radicals play an important role. Objective: The aim of this study was to investigate the role ofa hydroxyl radicals (ㆍOH)-modified antioxidant enzyme,superoxide dismutase (SOD), in AA autoimmunity. Methods:SOD was modified by ㆍOH radicals. Binding characteristicsof autoantibodies in AA patients (n=26) against ㆍOHmodifiedSOD (ㆍOH-SOD) were evaluated by immunoassaysand the results were compared with those of healthy,age-matched controls (n=30). The effects of ㆍOH radicalson immunoglobulin G (IgG) isolated from AA patients werestudied. Results: Highly specific binding to ㆍOH-SOD wasobserved in 32% of the samples of patient sera, whereasnormal human sera showed negligible binding with eitherantigen. Competitive inhibition immunoassays reiteratedthe results from direct binding. Protein-A-purified IgG fromAA patients (AA-IgG) also showed strong binding to ㆍOHSODas compared to IgG from normal human controls (p<0.001). In addition, AA-IgG from patients with alopeciauniversalis recognized ㆍOH-SOD to a greater extent thandid AA-IgG from patients with the patchy, persistent type ofalopecia. Furthermore, sera from AA patients had lowerlevels of SOD activity as compared to control sera. Conclusion: This is the first report showing an associationbetween ㆍOH-modified SOD and AA. These novel resultsdemonstrate that ㆍOH radical-mediated changes in SODpresent unique neo-epitopes that might contribute toantigen-driven antibody induction in AA.
Abstract
Background: Alopecia areata (AA) is a common form oflocalized, non-scarring hair loss. The cause of AA isunknown but reports suggest an autoimmune etiology,where oxygen free radicals play an important role. Objective: The aim of this study was to investigate the role ofa hydroxyl radicals (ㆍOH)-modified antioxidant enzyme,superoxide dismutase (SOD), in AA autoimmunity. Methods:SOD was modified by ㆍOH radicals. Binding characteristicsof autoantibodies in AA patients (n=26) against ㆍOHmodifiedSOD (ㆍOH-SOD) were evaluated by immunoassaysand the results were compared with those of healthy,age-matched controls (n=30). The effects of ㆍOH radicalson immunoglobulin G (IgG) isolated from AA patients werestudied. Results: Highly specific binding to ㆍOH-SOD wasobserved in 32% of the samples of patient sera, whereasnormal human sera showed negligible binding with eitherantigen. Competitive inhibition immunoassays reiteratedthe results from direct binding. Protein-A-purified IgG fromAA patients (AA-IgG) also showed strong binding to ㆍOHSODas compared to IgG from normal human controls (p<0.001). In addition, AA-IgG from patients with alopeciauniversalis recognized ㆍOH-SOD to a greater extent thandid AA-IgG from patients with the patchy, persistent type ofalopecia. Furthermore, sera from AA patients had lowerlevels of SOD activity as compared to control sera. Conclusion: This is the first report showing an associationbetween ㆍOH-modified SOD and AA. These novel resultsdemonstrate that ㆍOH radical-mediated changes in SODpresent unique neo-epitopes that might contribute toantigen-driven antibody induction in AA.
참고문헌 (33)
- Delamere FM, "Interventions for alopecia areata", Cochrane Database Syst Rev, (2), pp.CD004413~ (2008)
- Alkhalifah A, "Alopecia areata update", Dermatol Clin, 31, pp.93~108 (2013)
- Bertolini M, "Alopecia areata as a model for T cell-dependent autoimmune diseases", Exp Dermatol, 21, pp.477~479 (2012)
- Seetharam KA, "Alopecia areata: an update", Indian J Dermatol Venereol Leprol, 79, pp.563~575 (2013)
- Thomas EA, "Alopecia areata and autoimmunity:a clinical study", Indian J Dermatol, 53, pp.70~74 (2008)
- Hordinsky M, "Autoimmunity: alopecia areata", J Investig Dermatol Symp Proc, 9, pp.73~78 (2004)
- Kim SW, "Evaluation of free oxygen radical and antioxidant capacity in alopecia areata", J Dermatol, 37, pp.762~764 (2010)
- Abdel Fattah NS, "Lipid peroxidation", antioxidant activity in patients with alopecia areata, 2011, pp.25, 403~408
- Akar A, "Antioxidant enzymes and lipid peroxidation in the scalp of patients with alopecia areata", J Dermatol Sci, 29, pp.85~90 (2002)
- Bilgili SG, "Serum paraoxonase activity and oxidative status in subjects with alopecia areata", Cutan Ocul Toxicol, 32, pp.290~293 (2013)
- Al-Shobaili HA, "Biochemical markers of oxidative and nitrosative stress in acne vulgaris: correlation with disease activity", J Clin Lab Anal, 27, pp.45~52 (2013)
- Rasheed Z, "Preferential recognition of peroxynitrite damaged thymidine-monophosphate by anti-DNA autoantibodies in systemic lupus erythematosus", Nucleosides Nucleotides Nucleic Acids, 31, pp.736~751 (2012)
- Bakry OA, "Oxidative stress in alopecia areata: a case-control study", Am J Clin Dermatol, 15, pp.57~64 (2014)
- Namazi MR, "Nitric oxide donors as potential additions to anti-alopecia areata armamentarium", Inflamm Res, 52, pp.227~229 (2003)
- Koca R, "Evaluation of lipid peroxidation, oxidant", antioxidant status, and serum nitric oxide levels in alopecia areata, 2005, pp.11, CR296~CR299
- Al-Shobaili HA, "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", Dis Markers, 33, pp.19~34 (2012)
- Rasheed Z, "Reactive oxygen species damaged human serum albumin in patients with hepatocellular carcinoma", J Exp Clin Cancer Res, 26, pp.395~404 (2007)
- Rasheed Z, "Enhanced recognition of reactive oxygen species damaged human serum albumin by circulating systemic lupus erythematosus autoantibodies", Autoimmunity, 40, pp.512~520 (2007)
- Peixoto EB, "Antioxidant SOD mimetic prevents NADPH oxidase-induced oxidative stress and renal damage in the early stage of experimental diabetes and hypertension", Am J Nephrol, 29, pp.309~318 (2009)
- Al-Shobaili HA, "Immunological studies of oxidized superoxide dismutase in patients with systemic lupus erythematosus. Correlation with disease induction and progression", Saudi Med J, 33, pp.1177~1184 (2012)
- Olsen E, "Alopecia areata investigational assessment guidelines. National Alopecia Areata Foundation", J Am Acad Dermatol, 40, pp.242~246 (1999)
- Rasheed Z, "Hydroxyl radical damaged immunoglobulin G in patients with rheumatoid arthritis: biochemical and immunological studies", Clin Biochem, 41, pp.663~669 (2008)
- Goding JW, "Use of staphylococcal protein A as an immunological reagent", J Immunol Methods, 20, pp.241~253 (1978)
- Alzolibani AA, "4-Hydroxy-2-nonenal modified histone-H2A: a possible antigenic stimulus for systemic lupus erythematosus autoantibodies", Cell Immunol, 284, pp.154~162 (2013)
- Rasheed Z, "Immunological functions of oxidized human immunoglobulin G in type 1diabetes mellitus:its potential role in diabetic smokers as a biomarker of elevated oxidative stress", Dis Markers, 31, pp.47~54 (2011)
- Al-Shobaili HA, "Immunological studies of reactive oxygen species damaged catalase in patients with systemic lupus erythematosus:correlation with disease activity index", Immunol Invest, 42, pp.191~203 (2013)
- Rasheed Z, "Reactive oxygen species damaged human serum albumin in patients with type 1 diabetes mellitus:biochemical and immunological studies", Life Sci, 79, pp.2320~2328 (2006)
- Rasheed Z, "Structure and immunological function of oxidised albumin in lung cancer: its potential role as a biomarker of elevated oxidative stress", Br J Biomed Sci, 66, pp.67~73 (2009)
- Kutner A, "Hair loss in the dermatology office:an update on alopecia areata", J Drugs Dermatol, 12, pp.588~593 (2013)
- Tosti A, "Treatment strategies for alopecia", Expert Opin Pharmacother, 10, pp.1017~1026 (2009)
- Naziroglu M, "Antioxidants and lipid peroxidation status in the blood of patients with alopecia", Cell Biochem Funct, 18, pp.169~173 (2000)
- Batinić-Haberle I, "Superoxide dismutase mimics: chemistry, pharmacology, and therapeutic potential", Antioxid Redox Signal, 13, pp.877~918 (2010)
- Johnson F, "Superoxide dismutases and their impact upon human health", Mol Aspects Med, 26, pp.340~352 (2005)
