Vitiligo Autoimmunity Research Articles

Possible roles of B lymphocyte activating factor of the tumour necrosis factor family in vitiligo autoimmunity

Vitiligo is a cutaneous pigmentary disorder characterized by the loss of epidermal melanocytes. Strong evidence supports the theory that autoimmune mechanisms, namely B cell auto-antibody production and auto-reactive T cell cytotoxicity, are involved in this affliction. It is well known that autoimmunity results from a breakdown of self-tolerance. However, the mechanism which leads to the break-down of self-tolerance and subsequently causes the development of autoimmunity in vitiligo remains obscure. B lymphocyte activating factor of the tumour necrosis factor family is a recently identified ligand that is required for peripheral B-cell survival and homeostasis, the excessive production of which may lead to autoimmunity. Based on a collection of indirect evidences, we postulate that in individuals predisposed through inheritance, over-expression of the B lymphocyte activating factor may cause a breakdown of self-tolerance and subsequently cause autoimmune vitiligo via several possible mechanisms: B lymphocyte activating factor activates self-reactive B cells to produce auto-antibodies against melanocytes; these B cells may function as cellular adjuvants for the activation of the CD4+ T cells, enhancing their helper effect on the activation of the CD8+ T cells; CD4+ T cells assist CD8+ T cells to respond to melanocytes antigen, leading to the autoreactive reaction; B lymphocyte activating factor activated B cells capture antigen and present it directly to the CD8+ T cells; and, B lymphocyte activating factor delivers a complete costimulation signal to the T cells (both CD4+ and CD8+ subset), playing an additional role in the autoimmune response in vitiligo. Future challenges remain to test these propositions. Advancement in the treatment of vitiligo is still unsatisfactory, and thus novel modalities of therapy need to be developed. Recently, B lymphocyte activating factor has been evaluated as an attractive target for immune therapy. Once the hypothesis of B lymphocyte activating factor mediating the breakdown of self-tolerance in vitiligo is corroborated, it can become a novel target for treatment of vitiligo.

Abnormal expression of MHC class II and ICAM‐1 by melanocytes in vitiligo

The relationship between damage to cutaneous melanocytes and antimelanocyte autoimmunity in vitiligo is unclear. We have demonstrated abnormal expression of MHC class II molecules by perilesional melanocytes in 13/21 patients with vitiligo and a six-fold increase in the number expressing the intercellular adhesion molecule ICAM-1. These molecules have important roles in normal antigen presentation and activation of helper T lymphocytes, and their expression by melanocytes may contribute to the abnormal immune response in vitiligo. MHC class II is not expressed by melanocytes in psoriasis and is unlikely to be induced in vitiligo by cytokines released from activated non-melanocyte-specific T lymphocytes.

Autoimmune aspects of three skin diseases: pemphigus, cutaneous lupus erythematosus and vitiligo.

SummaryThis paper discusses three skin diseases due to or associated with autoimmunity: pemphigus vulgaris, cutaneous lupus erythematosus and vitiligo.In pemphigus vulgaris there is an autoantibody to an. antigen in. the inter‐epithelial or cell‐wall region of the prickle‐cell layer of stratified squamous epithelium. The site of reaction of this antibody corresponds with the acantholytic lesions of pemphigus vulgaris.In cutaneous lupus erythematosus antinuclear antibody may enter mildly damaged cells of stratified squamous epithelium and react with the cell nucleus. This results in the formation and deposition of antigen‐antibody complexes at the dermal‐epidermal junction, and these complexes may be distributed systemically and trapped in the kidney, causing glomerulonephritis. Thus the skin could be a site of primary importance in the genesis of the systemic lesions of lupus erythematosus.Vitiligo is known to coexist with a group of diseases which are clinically and serologically interrelated and are attributable to autoimmunity: pernicious anaemia, Hashimoto's thyroiditis and thyrotoxicosis, and adrenal atrophy. Striking clinical examples of these associations exist, but no specific autoantibody system is demonstrable. Hence the case for autoimmunity in vitiligo rests only on “guilt by association”.