Hydroxychloroquine protects melanocytes from autoantibody-induced injury by reducing the binding of antigen-antibody complexes

Li,Dong‑Guang; Hu,Wen‑Zhi; Ma,Hui‑Jun; Liu,Wen; Yang,Qing‑Qi; Zhao,Guang

doi:10.3892/mmr.2016.5354

August-2016 Volume 14 Issue 2

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August-2016 Volume 14 Issue 2

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Article

Hydroxychloroquine protects melanocytes from autoantibody-induced injury by reducing the binding of antigen-antibody complexes

Authors:
- Dong‑Guang Li
- Wen‑Zhi Hu
- Hui‑Jun Ma
- Wen Liu
- Qing‑Qi Yang
- Guang Zhao
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Affiliations: Department of Dermatology, The General Hospital of Air Force, Beijing 100142, P.R. China, Department of Dermatology, The 309th Hospital of Chinese PLA, Beijing 100091, P.R. China
Pages: 1275-1282
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Published online on: June 1, 2016

https://doi.org/10.3892/mmr.2016.5354
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Abstract

Vitiligo is a polygenic autoimmune disorder characterized by loss of pigmentation due to melanocyte destruction. Hydroxychloroquine (HCQ) is an effective immunosuppressant widely used in the treatment of autoimmune disorders. As generalized vitiligo (GV) is commonly considered to be a T cell and autoantibody-induced immune disorder, the present study aimed to determine whether HCQ protects melanocytes from autoantibody‑induced disruption. Anti‑melanocyte antibodies were obtained from the serum of patients with progressive GV and the effects of HCQ on prevent the autoantibody‑induced disruption of melanocytes was observed. Cell‑based ELISA, indirect immunofluorescence and western blotting were used to analyze the autoantibody content of sera samples obtained from 32 patients with progressive GV. The cytotoxicity of HCQ was detected by MTT assay, and 1 µg/ml HCQ was applied to human primary melanocytes (HMCs) to examine whether it could exert protective effects against autoantibody‑induced immune injury. Flow cytometry was used to measure autoantibody binding to the surface of HMCs. Complement‑dependent cytotoxicity (CDC) and antibody‑dependent cell‑mediated cytotoxicity (ADCC) were monitored by MTT and lactate dehydrogenase‑releasing assays. The concentration of autoantibodies in sera samples taken from GV patients was significantly higher than in controls, particularly in patients who had >10% of their body surface affected by vitiligo. The majority of the autoantibodies presented in the HMCs and human keratinocytes (HKCs) and were predominantly localized to the cell surface and cytoplasm. The molecular weights of the autoantigens were identified as 30, 37‑39, 42, 53, 60‑75, 90, 100, 110, and 126 kDa; the 30 kDa protein was observed only in HMCs. The addition of HCQ at a concentration of 1 µg/ml produced no significant cytotoxicity in HMCs and was demonstrated to reduce the binding of GV immunoglobulin G (IgG) to the surface of HMCs. HCQ also significantly decreased the effects of ADCC and CDC that were mediated by GV IgG. The present study provides evidence that HCQ dissociates autoantibody-antigen complexes on the surface of HMCs and reverses ADCC and CDC activity in vitro. Thus, in addition to its effectiveness as an antimalarial therapeutic agent, HCQ may also be a promising potential treatment for patients with vitiligo.

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1	Guerra L, Dellambra E, Brescia S and Raskovic D: Vitiligo: Pathogenetic hypotheses and targets for current therapies. Curr Drug Metab. 11:451–467. 2010. View Article : Google Scholar : PubMed/NCBI
2	Njoo MD and Westerhof W: Vitiligo: Pathogenesis and treatment. Am J Clin Dermatol. 2:167–181. 2001. View Article : Google Scholar
3	Michelsen D: The double strike hypothesis of the vitiligo pathomechanism: New approaches to vitiligo and melanoma. Med Hypotheses. 74:67–70. 2010. View Article : Google Scholar
4	Furst DE: Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases. Lupus. 5(Suppl 1): S11–S15. 1996. View Article : Google Scholar : PubMed/NCBI
5	Taïeb A and Picardo M; VETF Members: The definition and assessment of vitiligo: A consensus report of the Vitiligo European Task Force. Pigment Cell Res. 20:27–35. 2007. View Article : Google Scholar : PubMed/NCBI
6	Ma HJ, Yue XZ, Wang DG, Li CR and Zhu WY: A modified method for purifying amelanotic melanocytes from human hair follicles. J Dermatol. 33:239–248. 2006. View Article : Google Scholar : PubMed/NCBI
7	Cui J and Bystryn JC: Melanoma and vitiligo are associated with antibody responses to similar antigens on pigment cells. Arch Dermatol. 131:314–318. 1995. View Article : Google Scholar : PubMed/NCBI
8	Yu HS, Kao CH and Yu CL: Coexistence and relationship of antikeratinocyte and antimelanocyte antibodies in patients with non-segmental-type vitiligo. J Invest Dermatol. 100:823–828. 1993. View Article : Google Scholar : PubMed/NCBI
9	Ruiz-Argüelles A, Brito GJ, Reyes-Izquierdo P, Pérez-Romano B and Sánchez-Sosa S: Apoptosis of melanocytes in vitiligo results from antibody penetration. J Autoimmun. 29:281–286. 2007. View Article : Google Scholar : PubMed/NCBI
10	Fox RI: Mechanism of action of hydroxychloroquine as an anti-rheumatic drug. Semin Arthritis Rheum. 23(2 Suppl 1): S82–S91. 1993. View Article : Google Scholar
11	van den Borne BE, Dijkmans BA, de Rooij HH, le Cessie S and Verweij CL: Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells. J Rheumatol. 24:55–60. 1997.PubMed/NCBI
12	Rand JH, Wu XX, Quinn AS, Chen PP, Hathcock JJ and Taatjes DJ: Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers. Blood. 112:1687–1695. 2008. View Article : Google Scholar : PubMed/NCBI
13	Holtz G, Mantel W and Buck W: The inhibition of antigen-antibody reactions by chloroquine and its mechanism of action. Z Immunitatsforsch Exp Klin Immunol. 146:145–157. 1973.PubMed/NCBI
14	Costedoat-Chalumeau N, Amoura Z, Hulot JS, Aymard G, Leroux G, Marra D, Lechat P and Piette JC: Very low blood hydroxychloroquine concentration as an objective marker of poor adherence to treatment of systemic lupus erythematosus. Ann Rheum Dis. 66:821–824. 2007. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Hydroxychloroquine protects melanocytes from autoantibody-induced injury by reducing the binding of antigen-antibody complexes

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