Psoriasis patients generate increased serum levels of autoantibodies to tumor necrosis factor-α and interferon-α

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Abstract

Background

It has been shown in experimental animal models that were extended to humans that during autoimmune conditions, the immune system generates beneficial autoantibody (auto Ab) response to a limited number of inflammatory mediators that drive the pathogenesis of the disease.

Objective

To investigate the presence of auto Abs to cytokines and chemokines in psoriasis.

Methods

Sera were obtained from patients with psoriasis (n = 37), atopic dermatitis (AD) (n = 18) and healthy volunteers (n = 56). The titers of auto (Abs) to TNF-α, interferon-α (IFN-α), interleukin-17 (IL-17), and chemokines CCL2, CCL3 and CCL5 were determined using enzyme-linked immunosorbant assay. Neutralizing activities of high-titer auto Abs to TNF-α and IFN-α were determined using functional in vitro assays.

Results

Highly significant increased titers of auto Abs to TNF-α and IFN-α were detected in patients with psoriasis compared with healthy subjects and patients with AD (mean titers more than fourfold). These auto Abs demonstrated some neutralizing activity in vitro, but their serum levels did not correlate with the intensity and duration of the disease and with phototherapy induced remissions. Significantly increased titers albeit to a lesser extent, of auto Abs to CCL3 were detected in AD.

Conclusions

Psoriasis patients produce markedly increased levels of auto Abs to TNF-α and IFN-α which are two of the key cytokines in this disorder. The presence of these auto Abs which possess some neutralizing activity in vitro, may be an epiphenomenon or might play a role in attempting to suppress the ongoing inflammatory process.

Introduction

Psoriasis is a chronic, immunologically based inflammatory skin disease in which cytokines and chemokines released from cutaneous antigen-presenting cells, T cells and keratinocytes are believed to play a key role [1], [2]. Biological treatments that target cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL) 12/23 have shown effectiveness in controlling psoriasis [3], [4].

We have previously shown in experimental animal models that during different experimental autoimmune conditions, the immune system generates a beneficial autoantibody (auto Ab) response to a limited number of inflammatory mediators that drive the pathogenesis of each disease [5], [6], [7], [8], [9], [10], [11], [12], [13]. One of these studies which has been extended to human rheumatoid arthritis (RA) [11] showed that subjects with active RA, but not osteoarthritis (OA) develop a selective auto Ab response to TNF-α, but not to many other cytokines, even though they are expressed at the autoimmune site. Anti-TNF-α therapy is highly effective for RA, but not OA [14]. We sought to detect auto Abs against several pro-inflammatory cytokines and chemokines, most of which are believed to participate in psoriasis. Our results show for the first time that psoriasis patients produce highly significant increased levels of auto Abs against two of the key players in the pathogenesis of psoriasis: TNF-α and interferon-α (IFN-α) [2], and that these auto Abs demonstrate some neutralizing activity in vitro.

Section snippets

Study design and serum samples

The present study was conducted in accordance with the declaration of Helsinki (Institutional Review Board certification No 2577). Sera were collected from 37 patients with psoriasis vulgaris prior to phototherapy: 25 males and 12 females, aged 20–76 years (yrs), median 43.5 yrs; 18 patients with atopic dermatitis (AD): 10 males and 8 females, aged 19–69 yrs, median 30 yrs; and 56 healthy subjects (36 males and 20 females; aged 27–62 yrs, median 45.5 years). The psoriasis area and severity

Auto Abs to the cytokines and chemokines

Highly significant increased titers of auto Abs to TNF-α and IFN-α, but not to CCL2, CCL3 and CCL5 were detected in the sera of the psoriasis patients compared with the healthy subjects (p < 0.0001) and AD patients (p = 0.002 and 0.0004, respectively) (Fig. 1, Fig. 2). The mean titers of these two auto Abs in the psoriasis group were more than fourfold the mean titers in the other two groups (Fig. 1, Fig. 2). The serum titers of IL-17 of the psoriasis patients were borderline significantly

Discussion

The present study demonstrated that psoriasis patients generate markedly increased serum levels of auto Abs against TNF-α and IFN-α compared to AD patients and healthy subjects, and that these auto Abs demonstrate some neutralizing activity in vitro. Significantly increased levels of anti-TNF-α auto Abs have been recently demonstrated by our group in patients suffering from RA compared with patients with OA and healthy controls [11]. Furthermore, TNF-α specific auto Abs produced in rats with

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