Commentary 3
Makaleler > Tam Makale · 2008
Yazarlar: Huseyin Onay
Experimental Dermatology, Uluslararası, Wos, 2008, cilt 17, ss 153-154
DOI: 10.1111/j.1600-0625.2007.00666_8.x
Özet
Mannose-binding lectin (MBL) is one of the infamous foot soldiers that defend the body against micro-organisms in the never-ending ‘trench warfare’ fought within the body’s perimeter. It fights on four different fronts: (1) complement activation; (2) opsonophagocytosis; (3) modulation of inflammatory response; and (4) the promotion of apoptosis (1–3). Poorly equipped or insufficient numbers of soldiers are not capable of operating effectively and allow attacking micro-organisms to infiltrate the body which trigger a series of events resulting in the destruction of the body (autoimmune diseases) as is stated by Werth et al. Cleaning up the battlefield (clearance of the apoptotic cells) after the war between the micro-organisms and the immune-competent cells is one of the soldiers’ main functions (4). Inefficient clearance leads to a harmful autoimmune response (5,6). The MBL infantry plays a role in controlling the body’s overreactions represented by proinflammatory cytokines and the clearance of immune response remnants, such as immune complexes and adhesion molecules on inflammatory cells, which often lead to casualties on both sides (7,8). There have been a number of reports showing associations between MBL deficiency and autoimmune disorders such as systemic lupus erythematosus (SLE), dermatomyositis and cutaneous lupus erythematosus (4,9–11). In the process of vitiligo, there may be a specific antigenic stimulus which initiates the defensive actions of immune-competent cells in the skin. During these actions, a number of immune-competent skin cells go into apoptosis resulting in alterations of membrane carbohydrates. MBL has the ability to bind to these altered carbohydrates and to facilitate the clearance of apoptotic cells (4,6). Inadequate clearance of the apoptotic cells may cause continuous stimulation of the immune system and antibody production resulting in vitiligous changes in the skin cells (Fig. 1). In the aetiopathogenesis of vitiligo, low serum MBL levels may be associated with the impaired defense in the first step of immune response and insufficient clearance of apoptotic cells resulting in autoimmune reactions in the skin cells. It has also been shown that there is insufficient calcium (Ca) uptake in melanocytes and keratinocytes from vitiliginous skin (12,13). The infantry’s (MBL) command and supply chain rely heavily on Ca uptake. We hypothesize that a weak supply and command chain (Ca) and insufficient infantry (MBL) may contribute to undesirable consequences of the war (vitiligo). Therefore, we consider that sufficient numbers of infantry (normal MBL alleles/levels) provide a strong level of protection on the war against vitiligo. A reduced infantry may also result in a predisposition to attack from specific viral agents such as cytomegalovirus, Epstein–Barr virus, hepatitis E, and of course, the AIDS virus on weakened war fronts (14,15). For example, Grimes et al. identified cytomegalovirus DNA in skin biopsy specimens of patients with vitiligo (16). All of these notions support the idea that MBL deficiency may play an important role in susceptibility to vitiligo and replacement of deficient MBL may be helpful in combating vitiligo lesions and/or prevent its progression. Recently, recombinant human MBL (rMBL) has been produced (17) and a phase I study has been designed to evaluate the safety, tolerability, pharmakogenetic and immunogenetic profile of rMBL (18,19). In one of these, this phase I study no adverse effects of intravenous rMBL were observed in healthy but MBL deficient males (18). Protective role of mannose-binding lectin in a murine model of invasive pulmonary aspergillosis was also shown by Kaur et al. (20). Regarding the protective roles of normal MBL levels in patients with vitiligo, we propose that patients be treated with a topical application of a gel or pomade (name of it can be ‘vitiliMBL’) containing rMBL which is already available (17). We also consider the addition of Ca to this pomade or/and an increased Ca intake to be even more effective in the treatment of vitiligo.