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Assessment of serum levels of IgE in psoriasis: the relationship with clinical types of the disease

Lotfi, Ranya A.a; El-Sayed, Mahira H.a; El-Gabry, Shaymaa H.b

Journal of the Egyptian Women's Dermatologic Society: January 2015 - Volume 12 - Issue 1 - p 63–67
doi: 10.1097/01.EWX.0000450678.40084.23
Original articles
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Background Although it is believed that psoriasis vulgaris is a prototypic T helper 1 (Th1)-associated autoimmune disease, elevation in serum IgE in several cases of psoriasis has been reported. These observations suggest a possible shift from a Th1 to a Th2 cytokine response.

Objective To assess serum concentrations of total IgE in different types of psoriasis.

Patients and methods The study included 90 psoriatic patients (30 patients with chronic plaque psoriasis, 30 with erythrodermic psoriasis, and 30 with pustular psoriasis) and 30 healthy controls. Serum IgE levels were measured by the ELISA technique in the sera of all participants. The duration of psoriasis, the Psoriasis Area and Severity Index severity scoring, and the number of relapses were recorded in each patient.

Results The serum IgE level showed a statistically highly significant elevation in cases compared with controls (P≤0.01). A statistically highly significant difference was found between the four groups with regard to the median of the total serum IgE (P≤0.01), being the highest in erythrodermic psoriasis followed by pustular psoriasis, chronic plaque psoriasis, and then controls. A significant positive correlation was found between the total serum level of IgE and the Psoriasis Area and Severity Index score, the duration and the number of relapses in erythrodermic psoriasis only.

Conclusion The serum IgE level is significantly elevated in erythrodermic psoriatic patients, which may denote a shift from Th1- to Th2-directed immune mechanism.

Departments of aDermatology and Venereology, Faculty of Medicine, Ain Shams University

bEl Haud El-Marsoud Hospital, Cairo, Egypt

Correspondence to Ranya Adel Lotfi, MD, Department of Dermatology, Faculty of Medicine, Ain-Shams University, Cairo, Egypt Tel: +2010 0155 0123; e-mail: rkuku2000@yahoo.com

Received January 28, 2014

Accepted April 18, 2014

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Introduction

Psoriasis is a complex, multifactorial disease that appears to be influenced by genetic and immune-mediated components. It is a chronic inflammatory disease mediated by a complex interplay between the immune system and keratinocytes. Psoriasis is considered to be a mixed T helper 1 (Th1) and Th17 immune response 1. Although it is believed that psoriasis vulgaris is a prototypic Th1-associated autoimmune disease with an overexpression of proinflammatory cytokines produced by Th1 cells, elevation of serum IgE, the prototypical marker of Th2 immunity, has been reported in several cases of psoriasis 2–4.

It is now well established that the induction of IgE synthesis in human B cells requires three types of signals: the first signal is delivered through the B-cell antigen receptor; the second signal is provided primarily by cytokines derived from Th2 cells, for example, interleukin (IL)-4 and IL-13, which stimulate the transcription of IgE through the immunoglobulin constant region genes; and the third signal is provided through the interaction between the constitutively expressed CD40 molecule on B lymphocytes and CD154 (CD40 ligand), a molecule expressed on T lymphocytes after activation 5,6.

Several disorders are known to be associated with an imbalance between the Th1 and the Th2 arms of the cellular immune system as in atopic dermatitis, lichen planus, and systemic sclerosis 7. However, limited data are available regarding the altered Th1/Th2 balance in psoriasis. Many researchers have tried to explain the cause of increased IgE, the prototypical marker of Th2 immunity, in some cases of psoriasis, although it has always been known that psoriasis is a Th1 immune response. It appears that there is a relation between the serum level of IgE and psoriasis, whether Th2 immune response is incriminated in the pathogenesis of psoriasis or not.

Elevation of serum IgE is characteristic in common allergies including atopic eczema and allergic asthma, although increased levels of serum IgE are not necessarily associated with allergic symptoms.

The purpose of the current study was to assess the serum concentration of total IgE among the different types of psoriasis.

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Patients and methods

Patients

Ninety patients with psoriasis were included in this study, recruited from the Dermatology Outpatient Clinic, Ain-Shams University Hospital and El Houd El Marsoud Hospital, from March 2012 to March 2013. The control group consisted of 30 age and sex matched generally healthy participants.

In this case–control study, participants were divided into four groups:

  • Group 1: 30 patients with chronic plaque psoriasis (CPP).
  • Group 2: 30 patients with erythrodermic psoriasis (EP).
  • Group 3: 30 patients with pustular psoriasis (PP).
  • Group 4: 30 nonpsoriatic healthy volunteers serving as controls.

Exclusion criteria included a positive personal or family history of allergy, the presence of concomitant disorders including cardiovascular disease, systemic, viral and parasitic infections and neoplastic disease, and the use of systemic or topical corticosteroids before serum immunoglobulin assessment. Patients receiving phototherapy 6 months before this study were also excluded.

Participants were subjected to a thorough history taking, complete clinical examination (ENT and chest), determination of the duration and the number of previous relapses of psoriasis, careful dermatological examination to determine the type and the extent of psoriasis, and evaluation of the severity by the Psoriasis Area and Severity Index (PASI).

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The Psoriasis Area and Severity Index score

It is a score used for the determination of the severity of psoriasis in relation to three parameters including erythema (E), infiltration (I), and desquamation (D) 8.

All participants gave written informed consent after full explanation of the purpose and the nature of the study and all procedures. The study was approved by the Ain-Shams University Ethics Committee.

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Methods

From each participant, a minimum of 3 ml of venous blood was drawn under complete aseptic conditions. They were subjected to the determination of the total serum IgE level using the IgE Quantitative Enzyme Immunoassay Technique ELISA Kit (ImmunoSpec Corporation; Canogo Park, California, USA).

The assay system utilizes one anti-IgE antibody for solid-phase (microtiter wells) immobilization and another anti-IgE antibody in the antibody–enzyme (horseradish peroxidase) conjugate solution. The test specimen (serum) is added to IgE antibody-coated microtiter wells and incubated with the zero buffer. If human IgE is present in the specimen, it will combine with the antibody on the well. The well is then washed to remove any residual test specimen, and IgE antibody labeled with horseradish peroxidase (conjugate) is added. The conjugate will bind immunologically to the IgE on the well, resulting in the IgE molecules being sandwiched between the solid-phase and the enzyme-linked antibodies. After incubation at room temperature, the wells are washed with water to remove unbound labeled antibodies. 3,3′,5,5′-Tetramethyl benzidine is added and incubated for 20 min, resulting in the development of a blue color. The color development is stopped with the addition of 2 N HCl, and the color is changed to yellow and measured spectrophotometrically at 450 nm. The concentration of IgE is directly proportional to the color intensity of the test sample.

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Statistical analysis

The collected data were revised, coded, tabulated, and introduced to a PC using the statistical package for the social sciences (SPSS 15.0, 2001; SPSS Inc., Chicago, Illinois, USA) for Windows. Statistical analysis was performed using the Mann–Whitney U-test for two independent samples, The Kruskal–Wallis test for multiple independent samples, the χ2-test to examine the relationship between two qualitative variables and correlation analysis were performed by calculating the Spearman coefficient correlation. A P value of 0.05 or less was considered statistically significant and P value of 0.01 or less was considered highly significant.

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Results

The study included 90 psoriatic patients and 30 control participants. The patients were divided into three groups (30 patients with CPP, 30 with EP, and 30 with PP). There were 55 (61.1%) male and 35 (38.8%) female patients. Their age ranged from 10 to 75 years, with a mean of 41.8 years.

The control group consisted of 30 generally healthy participants: 17 (56.7%) men and 13 (43.3%) women with an age range of 24–72 years and a mean age of 40.16 years.

The number or percentage of patients who had an increased IgE level was highest with EP [17 (56.7%)], followed by PP [seven (23.3%)], and then CPP [six (20%)] and no increase in the total serum IgE was detected in the control group, with a highly statistical difference between them (P≤0.01).

Comparison between cases and controls with regard to the median of the serum level of total IgE levels (IU/ml) showed a statistically highly significant elevation in cases (87.5 IU/ml) compared with controls (24 IU/ml) (P≤0.01).

No relation was found between the serum level of IgE and age, sex, or a family history of psoriasis.

Statistical comparison between the four groups with regard to the median of the serum level of total IgE was highly significant (P≤0.01) (Table 1), being the highest in EP followed by PP, CPP, and then controls.

Table 1

Table 1

No statistically significant differences were found among psoriasis groups regarding the PASI score (P>0.05), which were 27.3, 30.4, and 32, in CPP, EP, and PP, respectively.

A direct highly significant positive correlation between the disease duration and serum levels of total IgE was found in EP (r=0.52, P<0.01) (Fig. 1). In contrast, such a correlation was not found in PP or CPP. A direct significant positive correlation between the PASI score and serum levels of total IgE was found among EP (r−0.45, P<0.05) (Fig. 2). However, such a correlation was not found among CPP or PP. Again, a direct highly significant positive correlation was found between serum levels of total IgE and the number of relapses in EP (r=0.54, P<0.01) (Fig. 3), whereas no correlation was found among patients with CPP and PP (Table 2).

Figure 1

Figure 1

Figure 2

Figure 2

Figure 3

Figure 3

Table 2

Table 2

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Discussion

Previous data on serum IgE in patients with psoriasis are very limited and results are controversial. Therefore, the aim of this work was to assess the total serum levels of IgE in psoriasis, and compare its levels between patients with EP, PP, CPP and healthy individuals.

Comparison between patients and controls revealed that there was a highly significant difference between both groups with regard to the median total serum IgE. These findings most likely indicate the possible association of IgE and psoriasis.

Results of this study demonstrated that the median serum level of total IgE was significantly elevated in 33.3% of psoriatic patients, being the highest in EP followed by PP and CPP, and the statistical difference between them was highly significant.

Elevation of serum IgE has been reported in several types of erythroderma with different etiopathogeneses; hence, it is worth mentioning that serum hyper-IgE may be a common phenomenon in erythroderma, including EP, no matter its pathogenesis. It may be explained by the diffuse dermatitis, which is a common feature in erythroderma. This dermatitis leads to a loss of integrity of the epidermal layer, resulting in epicutaneous sensitization to antigens and subsequent induction of a strong Th2 cell response, and this might underlie the elevated IgE levels that are seen in different etiologies of erythroderma such as EP, atopic dermatitis, hyper-IgE syndrome, and Netherton’s syndrome 2,9.

The concomitant occurrence of psoriasis and atopy has been reported by Pigatto 10. They stated that the production of cytokines of Th1 lymphocytes occurs during the early phase of psoriasis, whereas the cytokines of Th2 lymphocytes are active during the stable plaque-type phase and hence is more associated with IgE-mediated allergies. Therefore, in clinical practice, patients with chronic psoriasis are more likely to develop IgE-mediated diseases, whereas in the active phase, they will be more likely to be affected by contact dermatitis 11.

A recent comprehensive genome-wide association study provides support for the association of psoriasis with the IL23R gene and the zinc-finger protein 313 (ZNF313) within the nuclear factor κB pathway and of a genetic region that is potentially involved in the modulation of Th2 immune responses to enhance the transcription of Cε germline transcripts through nuclear factor κB, which leads to the rearrangement of the IgE genomic locus and the production of IgE antibodies 12,13.

In the current study, there was a direct statistically significant positive correlation between the serum level of total IgE and the PASI score, the duration of the disease and the number of relapses of psoriasis among EP. These findings are consistent and can be explained by another study performed by Jain et al. 14, which was conducted to assess the systemic Th1/Th2 imbalance in Indian psoriasis patients presenting with variable durations of the disease. Interferon γ (IFN-γ) for a Th1 response and IL-4 and IL-10 for a Th2 response were assayed. The study showed significant elevation of IFN-γ levels in patients presenting with either the first episode or up to five relapses of the disease, which indicates an active Th1 (type 1) immune response occurring during the early course of the disease. However, it was observed that IFN-γ levels waned in patients presenting with more than five relapses of the disease, and they were associated with a significant increase in IL-10 production, which may inhibit type 1 cytokine production. This suggests a shift in the polarization from a Th1-type to a more chronic Th2-type immune response.

In allergic diseases such as atopic eczema, overproduction of IgE is usually associated with a Th2 immune pattern, whereas in psoriasis, the Th1/Th17 immune response prevails, which is characterized by the production of the signature cytokine IL-17A.

In the current study, the number or percentage of patients who had an increased IgE level was highest with EP [17 (56.7%)], followed by PP [seven (23.3%)], and then CPP [six (20%)], and no increase in the total serum IgE was detected in the control group, with a highly statistical difference between them. Comparison between each group with the control regarding the median of serum level of total IgE showed a statistically nonsignificant difference between CPP and control, a statistically highly significant difference between EP and control, and a statistically significant difference between PP and control. In accordance with our results, Ding et al.15 found an elevation in the serum IgE level in 76.2% of the patients with generalized PP and 46% of the patients with psoriasis vulgaris. The study assumed that IL-17A causes neutrophil influx and regulates neutrophil-mediated inflammatory responses, the latter being more prominent in generalized pustular psoriasis than in psoriasis vulgaris, and assumed that IL-17A could directly promote the differentiation of IgE-secreting cells and IgE production. Hence, in contrast to previous studies 14, they suggested 15 that a shift from Th1 to Th2 may not be present in patients with psoriasis who have increased IgE levels.

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Conclusion

This study supports the evidence that elevation of total serum IgE is associated with psoriasis, especially EP. Additional studies are clearly warranted to verify mechanisms of such a phenomenon.

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Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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References

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Keywords:

IgE; psoriasis; serum

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