Molecular defects in the mannose binding lectin pathway in dermatological disease: Case report and literature review

The skin represents the largest organ of the innate immune system, composing not only a physical barrier but also containing numerous elements important in the immunological response against invading pathogens (e.g. keratinocytes, macrophages, Langerhans cells, dendritic cells, dermal fibroblasts). Damage to this barrier predisposes the body to a more susceptible environment for microbial dissemination, while improper immune surveillance can be a triggering factor for several inflammatory skin diseases [1]. This is an intricately orchestrated defense system constituted by a local response at the level of the epidermis and dermis, as well as by systemic involvement, with migration of additional immune cells to the site of antigenic stimulus.A member of the collectin group of pattern recognition receptors, mannose-binding lectin (MBL) is part of the innate immune system, a primordial defense mechanism that serves as the initial response to host invasion by pathogens in an antibody-independent fashion (Figure 1). This is achieved through direct opsonization of bacteria, recruitment of phagocytic cells that promote phagocytosis of pathogens, along with complement activation and immunomodulatory cytokine production that promote chemotaxis and recruitment of inflammatory cells, thereby limiting pathogenic spread. Defective MBL production is regarded as the most common immune deficiency in the general population, affecting approximately 5-7% of individuals [2], although some descriptions have delineated higher figures among Caucasians (up to 30%) [3]. The implications of low MBL levels have been the target of a large volume of research, with an unequivocal influence on host susceptibility to a variety of recurrent infectious processes and autoimmune disorders. However, propensity to dermatological disease has not been explored to any great extent. One report using MBL-deficient mice demonstrated upregulation of inflammatory cytokines and chemokines, thinning of the dermis