Analysis of Th1/Th2 response pattern for erythrodermic psoriasis

Abstract

As one of the most serious types of psoriasis, pathogenesis of erythrodermic psoriasis (EP) is unclear so far. In this study, we aimed to detect the levels of Th1/Th2 cytokine-associated transcription factors and T-lymphocyte clone in peripheral blood mononuclear cells (PBMCs) derived from EP patients, and gene expression level of T-bet/GATA-3 in skin lesion. The potential role of Th1/Th2 reaction pattern played in the pathogenesis of EP was also discussed. Serum levels of IFN-γ, IL-2, IL-4 and IL-10 were quantified by ELISA among 16 EP patients, 20 psoriasis vulgaris (PV) patients and 15 healthy controls. The expression levels of T-bet/GATA-3 in the skin lesion and PBMCs were examined by real-time qPCR. The ratio of Th1/Th2 was measured by flow cytometry. The levels of IFN-γ, IL-2, IL-4 and IL-10 were higher in EP patients than in the healthy controls. The levels of IL-4 and IL-10 were 69.44±11.45 and 12.62±4.57 pg/mL, respectively, in EP patients, significantly higher than those in PV patients and healthy controls (P<0.05). Flow cytometry revealed the levels of both Th1 and Th2 in PBMCs from EP patients were higher than those in healthy controls, and the Th1/Th2 ratio was dramatically lower than in PV patients (P<0.01). The ratios of IFN-γ/IL-4 and T-bet/GATA-3 in EP patients were both less than 1.0, suggesting a reversal when compared with the other two groups. Our study indicated that the EP patients exerted a Th1/Th2 bidirectional response pattern, and the balance of Th cell subsets inclines to Th2, which might be one of the important mechanisms of EP pathogenesis.

Erythrodermic Psoriasis: Current and Future Role of Biologicals

“…A similar assumption could justify the high level of immunoglobulin E (IgE) found in some EP patients [12,13]. The importance of Th2 response in EP is supported by evidence observed in a recent study in 16 EP patients: (1) Th1/Th2 ratio in peripheral blood significantly lower in EP patients than in those affected by psoriasis vulgaris; (2) higher serum levels of interleukin (IL)-4 and -10, two important Th2 cytokines, in subjects with EP compared with patients with psoriasis vulgaris and a healthy control group; (3) inverted ratios (\1.0) of both interferon (IFN)-c/IL-4 (serum levels) and T-bet/GATA-3 (levels in both skin lesions and peripheral blood mononuclear cells) in EP patients [12]. However, contrary to such findings, based on analysis of cytokine synthesis capability in peripheral blood T cells in an EP patient, some authors have speculated that a remarkable increase of Th1 cytokines such as IL-2 and IFN-c might be responsible for the development of erythroderma in psoriatic subjects, while a shift towards type 2 cytokine predominance would contribute to its resolution [14,15], as previously hypothesized for the improvement of plaquetype psoriasis [16].…”

“…Serious side effects directly related to acitretin therapy in EP would seem uncommon given that only a case of severe myopathy of all four limbs (arose after 2 weeks of treatment) has been reported [25]. However, the remarkable ability of acitretin to cause cutaneous fragility on erythrodermic skin, with consequent increased risk of S. aureus colonization [1], should be taken into account in EP patients since they are notorious for having an intrinsic increased susceptibility to developing sepsis due to such microorganisms [1,8,12]. Cyclosporine is commonly considered the classic firstline therapy for severe unstable cases of EP because of its rapid onset of action.…”

“…Some authors state that, although both T helper (Th)-1 and -2 lymphocytes are involved in the pathogenesis of EP, such forms of psoriasis would be characterized by a Th1/Th2 imbalance with a relatively weak expression of Th1 and greater Th2 advantage [12]. A similar assumption could justify the high level of immunoglobulin E (IgE) found in some EP patients [12,13].…”

“…Some authors state that, although both T helper (Th)-1 and -2 lymphocytes are involved in the pathogenesis of EP, such forms of psoriasis would be characterized by a Th1/Th2 imbalance with a relatively weak expression of Th1 and greater Th2 advantage [12]. A similar assumption could justify the high level of immunoglobulin E (IgE) found in some EP patients [12,13]. The importance of Th2 response in EP is supported by evidence observed in a recent study in 16 EP patients: (1) Th1/Th2 ratio in peripheral blood significantly lower in EP patients than in those affected by psoriasis vulgaris; (2) higher serum levels of interleukin (IL)-4 and -10, two important Th2 cytokines, in subjects with EP compared with patients with psoriasis vulgaris and a healthy control group; (3) inverted ratios (\1.0) of both interferon (IFN)-c/IL-4 (serum levels) and T-bet/GATA-3 (levels in both skin lesions and peripheral blood mononuclear cells) in EP patients [12].…”

“…Recent evidence suggests that biological agents, including both anti-tumor necrosis factor (TNF)-a agents and ustekinumab, may be more useful in the management of EP [2,8,12,20]. Unfortunately, subjects with EP are usually excluded from all pivotal trials involving biological agents, and this evidence is currently dispersed in small case series and single case reports.…”