Recognition of oxidized albumin and thyroid antigens by psoriasis autoantibodies: A possible role of reactive-oxygen-species induced epitopes in chronic plaque psoriasis

Objectives:

To investigate the role of reactive-oxygen-species (ROS) induced epitopes on human-serum-albumin (HSA) and thyroid antigens in psoriasis autoimmunity.

Methods:

This study was performed in the College of Medicine, Qassim University, Buraidah, Saudi Arabia between May 2014 and February 2015. The study was designed to explore the role of ROS-induced epitopes in psoriasis autoimmunity. Singlet-oxygen (or ROS)-induced epitopes on protein (ROS-epitopes-albumin) was characterized by in-vitro and in-vivo. Thyroid antigens were prepared from rabbit thyroid, and thyroglobulin was isolated from thyroid extract. Immunocross-reactions of protein-A purified anti-ROS-epitopes-HSA-immunoglobulin G (IgGs) with thyroid antigen, thyroglobulin, and their oxidized forms were determined. Binding characteristics of autoantibodies in chronic plaque psoriasis patients (n=26) against ROS-epitopes-HSA and also with native and oxidized thyroid antigens were screened, and the results were compared with age-matched controls (n=22).

Results:

The anti-ROS-epitopes-HSA-IgGs showed cross-reactions with thyroid antigen, thyroglobulin and with their oxidized forms. High degree of specific binding by psoriasis IgGs to ROS-epitopes-HSA, ROS-thyroid antigen and ROS-thyroglobulin was observed. Immunoglobulin G from normal-human-controls showed negligible binding with all tested antigens. Moreover, sera from psoriasis patients had higher levels of carbonyl contents compared with control sera.

Conclusion:

Structural alterations in albumin, thyroid antigens by ROS, generate unique neo-epitopes that might be one of the factors for the induction of autoantibodies in psoriasis.Psoriasis, a chronic skin disorder is known to be the most prevalent autoimmune disorder in humans.1 It is characterized by hyperplasia of the epidermis, infiltration of leukocytes of dermis and epidermis as well as dilatation and proliferation of blood vessels, which are likely to be triggered by multiple factors such as drugs, physical and psychological stress, bacterial infections, or injury.2 Psoriasis appears in different clinical variants and the most frequently is the plaque psoriasis (also known as psoriasis vulgaris), presents with scaly red plaques on common areas, such as on scalp, the back, dorsal skin of the elbows, and ventral skin of knees.3 Although, the role of immunologic and environmental factors in the pathogenesis of plaques psoriasis has been proposed, but the precise etiology of disease remains poorly understood.1,3 It is well documented that oxidative stress is one of the major factors involved in the pathogenesis of psoriasis4-6 and now it has been well established that excess generation of reactive oxygen species (ROS) by the immune system play a vital role in the development of psoriasis.7 Cellular events such as cell proliferation, apoptosis, cell differentiation, and immune response are influenced by ROS, and these events are altered in psoriasis patients.4-7 Although the exact pathogenesis of psoriasis is unknown, but the occurrence of autoimmune reactions has been assumed,8-10 the presence of autoantibodies and various underlying immunologic abnormalities in the affected sites of these patients have also been reported.8,11-15 The autoimmune etiology has been also proposed on the basis of its association with various autoimmune diseases,8,10 but the precise mechanism of generation of autoantibodies in psoriasis remains unclear.Thyroid disorders have a high prevalence in medical practice; they are associated with a wide range of diseases with which they may or may not share etiological factors. One of the organs which best show this wide range of clinical signs of thyroid dysfunctions is the skin.16-18 Thyroid abnormalities are well documented in psoriasis patients, thyroid gland causes an increase of epidermal growth factor levels, which has an important role in keratinocytes proliferation in psoriasis.19-21 In addition, a high prevalence of thyroid associated autoimmunity has also been reported in patients with psoriasis.20 Moreover, elevated ROS levels are often seen to be associated with thyroid dysfunctions, and now it is proposed that the thyroid hormones influence the ROS steady-state environment in the cell.22-24 The most common idea is the hyperthyroidism, which enhances the ROS production that perturbs the ROS steady-state environment to facilitate the cellular damage or damage to the cellular components as also reported in psoriasis patients.22,25 Therefore, it is assumed that in psoriasis, cells or cellular components are continuously exposed to oxidative stress, so that alterations in conformation and function of these cellular components may occur, which may results in modification of their biological properties. In view of these, this study was aimed to investigate the role of ROS-induced epitopes on albumin and thyroid antigens in psoriasis autoimmunity. To test this, ROS-modified epitopes were generated on albumin and antibodies against ROS-modified-albumin (anti-ROS-modified-epitopes antibodies) were experimentally generated. Cross-reactions of affinity purified anti-ROS-modified-epitopes immunoglobulin Gs (IgGs) with native- and ROS- modified thyroid antigen, thyroglobulin or human DNA were determined. Our data showed that anti-ROS-modified-epitopes-IgGs showed immunospecificity with thyroid antigen, thyroglobulin and with their oxidized forms. Importantly, the antigen(s) binding characteristics of naturally occurring chronic plaque psoriasis antibodies to ROS-modified epitopes, thyroid antigen, ROS-modified thyroid antigen, thyroglobulin, ROS-modified thyroglobulin, human DNA, and ROS-modified human DNA were determined.