Current concepts in the immunopathogenesis of psoriasis

There is much evidence to support the concept that psoriasis is a type 1 autoimmune disease, primarily mediated by interferon gamma and other inflammatory cytokines. There has been renewed interest in the role of components of the innate immune system, however,and it may be that overlap between the innate and acquired arms of the immune system can better explain immunopathogenesis in psoriasis. Relevant cell types, receptors, and immune mediators within these traditional boundaries of the immune system are discussed.Finally, pathogenic contributions from important psoriatic mouse models and recent genomic data using the new gene chip technology are elaborated.     

Reviewing concepts in the immunopathogenesis of psoriasis

Insights into the pathogenesis of psoriasis led to the development of therapeutic tools aimed at blocking its immunological trigger. In parallel, cytokines such as the tumor necrosis factor (TNF) have been recognized as playing a crucial role in the pathogenesis of psoriasis and its associated comorbidities. Genetic and immunological studies have contributed effectively towards establishing the currently held concepts regarding this complex disease.     

Possible involvement of epidermodysplasia verruciformis human papillomaviruses in the immunopathogenesis of psoriasis: a proposed hypothesis

We have shown previously in psoriasis a very high prevalence of epidermodysplasia verruciforms-associated human papillomavirus 5 (EVHPV5) DNA and antibodies to human papillomavirus 5 (HPV5) virus-like particle (VLP) L1, and we suggested that this benign hyperproliferative disorder could be a reservoir for EVHPVs. Here we provide new data confirming the expression of EVHPVs in psoriasis and present our hypothesis on their possible involvement in the immunopathogenesis of the disorder. The new important finding was detection by radioimmunoprecipitation assay of a very high prevalence of antibodies to E6/E7 HPV5 oncoproteins, known to enhance keratinocyte proliferation. More recently, EV genes were identified, EVER1 and EVER2, whose mutations are responsible for epidermodysplasia verruciformis. Eidermodysplasia verruciforms-associated human papillomaviruses are harmless to the general population as a result of genetic restriction, which in psoriasis appears to be partly alleviated, and this may allow the viral gene expression. We hypothesize that induction of keratinocyte proliferation in psoriasis by various stimuli initiates the EVHPV life cycle with expression of early (E6/E7) and late (L1) viral proteins. The early proteins may, in turn, enhance the keratinocyte proliferation, and the late proteins could serve as target for specific-B- and T-cell-mediated responses. Immune responses against the viral antigens in the epidermis may result in the chemoattraction of leukocytes and Munro abscess formation, as well as in production of the psoriatic process. The novel immunomodulatory therapies could also inhibit immune responses against EVHPV proteins, leading to decreased cytokine production, keratinocyte proliferation and EVHPV expression. Thus the beneficial effect of these therapies is not discordant with the propose hypothesis of possible involvement of EVHPVs in the immunopathogenesis of psoriasis.     

Speculations on the immunopathogenesis of psoriasis: T-cell violation of a keratinocyte sphere of influence

The thesis is advanced that the differences in antigen processing and presentation described for "fresh" and "cultured" Langerhans cells in vitro reflect similar differences between intraepidermal and intranodal Langerhans cells in vivo. The functional properties of Langerhans cells are dependent upon the microenvironment in which they reside; thus, intraepidermal Langerhans cells are under the influence of cytokines secreted by keratinocytes, whereas intranodal Langerhans cells come under the influence of lymphokines from T lymphocytes. It is speculated that a genetic lesion in psoriasis robs keratinocytes of their capacity to create an "appropriate" epidermal microenvironment. As a consequence, intraepidermal Langerhans cells adopt the functional program of intranodal cells. When "uninvolved" psoriatic skin receives a cutaneous challenge with antigen, Langerhans cells, by activating naive T cells in situ, unwittingly engender a microenvironment that is more appropriate to a lymph node. This skin becomes "involved" as it gradually acquires features associated with lymph nodes (such as high endothelial venules). And the derangement is further complicated by abnormalities of proliferation and differentiation among keratinocytes and dermal fibroblasts as they respond to the inappropriate T-cell-derived lymphokines, giving rising to the typical, active psoriatic lesion.     

New developments in the treatment of psoriasis.

During the previous 10 years, important innovations have been developed in the treatment of psoriasis. Calcipotriol has been introduced in most countries already 10 years ago and more recently 2 other vitamin D(3) analogues have become available: calcitriol and tacalitol. In some countries, the topical retinoid tazarotene has been registered as a routine treatment in psoriasis. Evidence-based data on the efficacy and safety of combination treatments are accumulating. In particular, the combination of calcipotriol and topical corticosteroids has been shown to be very effective and safe. The combination of systemic treatments is controversial. In individual patients, the risk of combining major therapies should be balanced against the need to enhance efficacy in individuals. New leads in experimental treatments are new vitamin D(3) analogues and new retinoids as well as 4-hydroxylase- and 24-hydroxylase inhibitors. Important innovations in immunomodulatory treatments are: tacrolimus, ascomycine, anti-CD4, anti-CD25, peptide T and LFA3TIP.     

New systemic therapies of psoriasis

The metabolic-pathophysiological pathways are of prime importance when considering psoriasis therapy. Present-day concepts recognize that central growth hormone controls the metabolic route and that the peripheral pathway is under the control of several growth factors. Both the central and peripheral pathways induce pathological proliferation. A selection of six routine drugs, all with specific biochemical properties, induced part to total remission in about 75% of the 442 psoriasis patients.     

梅毒免疫学机制研究进展

在梅毒螺旋体感染的不同病期,细胞免疫和体液免疫均有部分涉及,目前认为主要与T细胞介导的免疫反应有关,血清抗体仅有部分保护作用,同时还存在不同程度的免疫抑制现象。梅毒早期出现的体液免疫和细胞免疫对梅毒螺旋体的清除起重要作用,而在晚期出现的细胞免疫反应则主要引起组织损害。本文就近年来关于梅毒螺旋体的免疫原性、感染梅毒后机体的免疫反应以及梅毒螺旋体免疫逃逸等方面的研究进展作一综述。     

New developments in our understanding of the biology of psoriasis

Increased keratinocyte proliferation and inflammation are two hallmarks of psoriasis. In this paper new developments in skin biology and biochemistry that help us to understand these two features of the disease are discussed. Methods to control proliferation and inflammation based on these scientific developments are presented.     

New trends in the use of metals in jewellery

Owing, on the one hand, to the constant increase in the %s of nickel sensitization in the majority of allergy departments of dermatology and, on the other, to the fact that sensitization to nickel is almost always through contact with jewellery and imitation jewellery, an update was carried out on the metal alloys principally used in the manufacture of such jewellery (earrings, bracelets, necklaces, rings, watch straps, etc.) The conclusions of this review demonstrate that nickel is irreplaceable in the majority of the alloys, because of its excellent technical properties and low price and, as a result, the % of sensitizations to this allergen will not only maintain their present high level but will probably increase in the future.