Menoufia Medical Journal

ORIGINAL ARTICLE
Year
: 2015  |  Volume : 28  |  Issue : 2  |  Page : 488--493

Assessment of serum interferon-γ in psoriasis


Mohamed A Shoeib1, Eman N El-Shafey1, Ahmed A Sonbol2, Shimaa E Radwan Lashin1,  
1 Department of Dermatology, Andrology and STDs, Menofiya University, Menofiya, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menofiya University, Menofiya, Egypt

Correspondence Address:
Shimaa E Radwan Lashin
Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menofiya University, Menofiya
Egypt

Abstract

Background Psoriasis is a common chronic, recurrent, and immune-mediated disease of the skin and joints that follows a relapsing and remitting course. Psoriasis represents a T-cell-mediated inflammatory skin disease that includes the activation of both Th1, which produces interferon-g (IFN-γ), tumor necrosis factor-α, and interleukin-2 (IL-2), and Th17, which produces IL-17, tumor necrosis factor-α, IL-6, and IL-22. Objective We planned this study to determine probable associations between IFN-γ, Th1 cytokine, in the sera of psoriatic patients and the possible correlation to disease severity. Materials and methods We studied the level of serum IFN-γ in 40 cases of plaque psoriasis, erythrodermic, and guttatepsoriasis using PASI score for assessing the severity, and in the serum of healthy 40 controls. Results There was a statistically significant positive correlation between the PASI score and the level of IFN-γ in all clinical types. This can suggest that serum IFN-g is a psoriasis severity and prognostic marker. Conclusion Serum IFN-γ in psoriatic patients can be used as a severity and prognostic marker, and then anti-IFN-γ may eventually become a useful therapeutic approach in psoriasis.



How to cite this article:
Shoeib MA, El-Shafey EN, Sonbol AA, Radwan Lashin SE. Assessment of serum interferon-γ in psoriasis.Menoufia Med J 2015;28:488-493


How to cite this URL:
Shoeib MA, El-Shafey EN, Sonbol AA, Radwan Lashin SE. Assessment of serum interferon-γ in psoriasis. Menoufia Med J [serial online] 2015 [cited 2020 Apr 3 ];28:488-493
Available from: http://www.mmj.eg.net/text.asp?2015/28/2/488/163907


Full Text

 Introduction



Psoriasis is a persistent chronic, relapsing, inflammatory, and hyperproliferative skin disorder affecting ~2-3% of the population. The most characteristic lesions consist of red scaly, sharply demarcated, indurated plaques [1].

Although the initial events triggering a psoriatic lesion are still unknown, many environmental factors have been shown to play a role in psoriasis pathogenesis. External triggers such as physical trauma, infection, stress, drug, and alcohol can trigger an initial episode of psoriasis in those individuals who already have a genetic predisposition [2] .

Psoriasis is a T-cell immune-mediated disease with a complex role for a variety of cytokine interactions between keratinocytes and T lymphocytes [3] .

Interferon-g (IFN-g) is a dimerized, soluble cytokine that is the only member of the type II class of IFNs [4] . IFN-g is a helper T-cell 1 (Th1)-derived cytokine and plays a critical role for both innate and adaptive immunity against viral and intracellular bacterial infections and for tumor control. In normal skin, IFN-g promotes growth arrest of normal keratinocytes [5] . It was suggested that IFN-g plays a role in many autoimmune diseases, including alopecia areata [6] , systemic lupus erythematosus [7] , and lichen planus [8] .

IFN-g is considered a key cytokine in the pathogenesis of psoriasis. The suggested mechanisms are that IFN-g mediates interactions between inflammatory T cells and keratinocytes, facilitating T-cell migration to lesional epidermis [9] . It induces antiapoptotic activity, thus promoting keratinocyte proliferation. IFN-g also enhances CD1d expression on keratinocytes that plays a major role in the development and activation of natural killer T cells [10] .

The aim of this study was to assess the level of serum IFN-g in psoriatic patients and its relation with the severity of the disease.

 Materials and methods



Patients

This study was conducted on 40 patients (32 male and eight female) suffering from plaque, erythrodermic, and guttate psoriasis, with age ranging from 12 to 76 years, attending Dermatology Clinic of Menofiya University Hospital. The patients did not receive any topical or systemic therapy before the study, and all patients were subjected to complete history taking, full general examination, and detailed dermatological examination, including assessment of PASI score [11] . They were compared with 40 age-matched and sex-matched healthy volunteers and blood donors. Venous blood samples (5-10 ml) were taken from patient and control groups under sterile conditions. Using the enzyme-linked immunosorbent assay (ELISA, USA) kit, serum IFN-g was measured.

Informed consent was obtained from all participants. This work had been approved by Ethics Committee of Menofiya University.

Immunoassay

All samples were received at the Department of Clinical Pathology, Faculty of Medicine, Menofiya University. The Assay Max Human IFN-g ELISA kits were used for the detection of human IFN-g in serum samples. This assay uses a quantitative sandwich enzyme immunoassay technique that measures human IFN-g in less than 5 h. IFN-g in standards and samples was sandwiched by the immobilized antibody and biotinylated polyclonal antibody specific for IFN-g, which was recognized by a streptavidin-peroxidase conjugate. All unbound material was then washed away and a peroxidase enzyme substrate was added. The color development was stopped and the intensity of the color was measured.

Evaluation

The absorbance was read on a microplate reader at a wavelength of 450 nm immediately. Then the mean value of the duplicate or triplicate readings for each standard and sample was calculated. A standard curve was generated by plotting the standard concentrations on the x-axis and the corresponding mean of 450 nm absorbance on the y-axis. The concentration of IFN-g in the samples was determined directly from this curve. The minimum detectable dose of IFN-g is typically 0.016 ng/ml. The normal value of serum IFN was 89-111 ng/ml (Assay Max).

Statistical analysis

Results were collected, tabulated, and statistically analyzed by IBM SPSS version 11. The types of statistics used were described, including mean (x), SD, percentage (%), range, and analytic statistics. These included:

χ2 -test, used for comparison between qualitative variable in different groups;Student's t-test, used for comparison between two groups having quantitative variables;Mann-Whitney U-test, used for comparison between two groups not normally distributed having quantitative variables;F-test, an analysis of variance test used for comparison between three groups of normally distributed variables; andPearson correlation (r) test, used to measure the association between two quantitative variables. P-value of less than 0.05 was considered statistically significant; high significance was considered when P-value was less than 0.001, and insignificance was considered when P-value was greater than 0.05.

 Results



The clinical data of cases and controls were shown in [Table 1].{Table 1}

There was no significant difference between psoriatic cases and control groups regarding age and sex (P > 0.05) [Table 2].{Table 2}

Regarding the level of IFN-g, it showed that the mean value of the level of IFN-g was highly significant (P < 0.001) in psoriatic cases compared with the control group [Table 3].{Table 3}

There was no significant statistical difference between male and female patients with regard to the PASI score (P > 0.05). Psoriasis subgroups with age below 40 years showed significant association with the PASI score (P < 0.05) compared with age above 40 years' subgroup. There was no significant association between family history and PASI score. There was a statistically significant association between nail affection and PASI score in the studied cases (P < 0.05), and there was no statistical difference between patients with Koebner's phenomenon regarding PASI score (P > 0.05) [Table 4].{Table 4}

There was no significant statistical difference between male and female patients with regard to the level of IFN (P > 0.05). There was no significant difference between psoriasis patients with age below 40 years compared with age above 40 years with regard to the level of IFN-g (P > 0.05). There was no significant association between family history and the level of IFN-g. There was a highly statistical significant association between nail affection and IFN level in the studied cases (P < 0.001), and there was no statistical difference between patients with Koebner's phenomenon with regard to the level of IFN (P > 0.05) [Table 5].{Table 5}

Psoriasis cases with severe PASI score showed highly significant elevated serum IFN-g (P < 0.001) compared with the moderate and mild cases [Table 6].{Table 6}

There was no significant difference between plaque and guttate psoriasis groups with regard to the PASI score and IFN level (P > 0.05). However, there was a significant difference between erythrodermic psoriasis group, on one hand, and both plaque and guttate psoriasis groups, on the other hand, in terms of the same parameters (P < 0.05) [Table 7].{Table 7}

 Discussion



Psoriasis is a chronic relapsing, complex inflammatory skin disease that affects 2-3% of the population worldwide. The most characteristic lesions consist of red scaly, sharply demarcated, indurated plaques present, particularly over the extensor surfaces and scalp. The disease is variable in extent, duration, and periodicity of flares [12] .

Although the initial events triggering a psoriatic lesion are still unknown, many environmental factors have been shown to play a role in psoriasis pathogenesis [13] . These triggers activate dendritic cells, such as Langerhans cell, inducing their migration to the skin-draining lymphatics. Here, antigen-specific T cells are primed by the migrated skin dendritic cells to differentiate into effector T cells, and then traffic to the skin, where they together induce the formation of a primary psoriatic plaque. During this step, some T cells and dendritic cells start to infiltrate the epidermis, releasing proinflammatory cytokines, which in turn stimulate keratinocyte proliferation. Psoriasis can be considered as a T-cell-mediated disease, complex role for a variety of cytokine interaction between keratinocytes, and T lymphocytes including IFN-g, leading to the production of psoriatic lesion [14] .

IFN-g is a helper T-cell 1 (Th1)-derived cytokine and plays a critical role for both innate and adaptive immunity. In normal skin, IFN-g promotes growth arrest of normal keratinocytes, normal differentiating epidermal keratinocytes in in-vitro culture undergo apoptosis when they are stimulated by IFN-g [15] . In psoriasis, it induces antiapoptotic protein BCLx and alters the expression of the apoptotic catalytic enzymes, cathepsin D and zinc-α2 glycoprotein, in psoriatic skin, thus promoting keratinocyte proliferation playing a major role in psoriasis pathogenesis [10] .

The aim of this study was to assess the level of serum IFN-g in psoriatic patients and its relationship with the severity of the disease.

In the present study, male patients were more affected than female patients. This was in agreement with the results of Arican et al. [16] and can be attributed to more male exposure to environmental factors that may increase the risk of psoriasis from two-fold to three-fold.

In the current study, there was a significant negative correlation between age and the severity of the disease. This can be explained by that the genetic predisposition in early-onset group can be related to increase in the severity of the disease. This result is in agreement with the results of Abdel-Hamid et al. [17] . In the present study, there is no correlation between age and serum level of IFN-g, and this agrees with the results of Arican et al. [16] .

In the current study, the mean value of serum levels of IFN-g were significantly higher in the group with psoriasis compared with the control group; this may provide evidence about its role in psoriasis pathogenesis. This result is in agreement with the result of Szegedi et al. [18] . The suggested mechanisms are that IFN-g is capable of inducing the expression of intercellular adhesion molecule 1 (ICAM-1) and HLA-DR, thus mediating interactions between inflammatory T cells and keratinocytes, facilitating T-cell migration to the lesional epidermis. IFN-g also stimulates the release of a number of cytokines, such as interleukin (IL-1), IL-6, IL-8, tumor necrosis factor-α, and inflammatory mediators, in addition to inducing the expression of ICAM-1, HLA-DR, and vascular ICAM-1 on keratinocytes and endothelial cells, thereby attracting lymphocytes from circulation. Hong et al. [19] suggested that IFN-g is mainly concerned with the promotion of keratinocyte proliferation, thus enhancing disease severity, and it is not essential for the induction and maintenance of pathogenic inflammatory Th1 cells.

In the current study, there was a significant positive correlation between PASI score and level of IFN-g in all clinical types and psoriasis cases, with severe PASI score showing highly significant elevated serum IFN-g (P < 0.001) compared with moderate and mild cases. This can suggest that serum IFN-g is a severity of psoriasis and prognostic marker, and this result is in agreement with the result of Abdallah et al. [20] . In contrast with our study, Almakhzangy and Gaballa [21] found no correlation between the PASI score and serum level of IFN-g. This explained that IFN-g has a role in psoriasis but not the proximal regulator or sole player in its pathogenesis. In addition to that, Abdel-Hamid et al. [17] concluded that IFN-g was inaccurate for testing disease severity.

In the present study, there was a significant difference between the erythrodermic psoriasis group, on one hand, and both plaque and guttate psoriasis groups, on the other hand, with regard to the IFN level and PASI score. This result is in agreement with the result of Abdallah et al. [20] .

In the current study, there was no association between the severity of the disease and level of IFN-g with regard to the Koebner's phenomenon. This agreed with the result of Griffiths [22] , who studied the effect of subcutaneous injection of recombinant human IFN-g in patients with psoriatic arthritis, and ~25% of treated participants developed foci of psoriasis at the injection sites. This reaction did not occur at the sites of saline injection, implying that the lesions did not develop because of the Koebner's phenomenon.

In the present study, there was a significant association between nail affection and severity of the disease. In addition, there was a highly significant association between nail affection and IFN-g in studied cases. This can be explained by the same mechanism of IFN-g in psoriasis. No similar results detected with or against these findings ([Figure 1] [Figure 2] [Figure 3] [Figure 4]).{Figure 1}{Figure 2}{Figure 3}{Figure 4}

 Conclusion



Serum IFN-g in psoriatic patients can be used as severity and prognostic marker; then, anti-IFN-g may eventually become a useful therapeutic approach in psoriasis.

 Acknowledgements



Conflicts of interest

There are no conflicts of interest.

References

1Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009; 361 : 496-509.
2Dika E, Bardazzi F, Balestri R, Maibach H. Enviromental factors and psoriasis. Curr Probl Dermatol 2007; 35 :118-135.
3Saha B, Jyothi Prasanna S, Chandrasekar B, Nandi D. Gene modulation and immunoregulatory roles of interferon gamma. Cytokine 2010; 50 :1-14.
4Bureau J, Bihl F, Brahic M, Le Paslier D. The gene coding for interferon gamma is linked to the D12S335 and D12S313 microsatellites and to the MDM2 gene. Genomics 1995; 28 :109-112.
5Saunders N, Jetten A. Control of growth regulatory and differentiation-specific genes in human epidermal keratinocytes by interferon gamma. Antagonism by retinoic acid and transforming growth factor β1. J Biol Chem 1994; 269 :2016-2022.
6to T, Ito N, Saathoff M, Bettermann A, Takigawa M, Paus R. Interferon-gamma is a potent inducer of catagen like changes in cultured human anagen hair follicles. Br J Dermatol 2005; 152 :623-631.
7Robak E, Smolewski P, Wozniacka A, Sysa-Jedrzejowska A, Stepieñ H, Robak T. Relationship between peripheral blood dendritic cells and cytokines involved in the pathogenesis of systemic lupus erythematosus. Eur Cytokine Netw 2004; 15 :222-230.
8Wenzel J, Tuting T. An IFN-associated cytotoxic cellular immune response against viral, self-, or tumor antigens is a common pathogenetic feature in "Interface Dermatitis". oerg.wenzel@ukb.unibonn.de, published online 17 April, 2008.
9Liu Y, Krueger JG, Bowcock A. Psoriasis: genetic associations and immune system changes. Genes Immun 2007; 8 :1-12.
10Nickoloff BJ, Nestle F. Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest 2004; 113 :1664-1675.
11Dawson B, Trapp R. Basic clinical biostatistics. 3rd ed. New York: Mc-Graw Hill; 2001.
12Griffiths C, Camp R, Barker J. Psoriasis. In: Rook's textbook of dermatology. Burns T, Breathnach S, Cox N, et al. 7th edition. Blackwell science 2004. 35 :1-62.
13Blauvet A. New concepts in the pathogenesis and treatment of psoriasis: key roles for Il-23, IL-17 and TOF-B1. Expert Rev Dermatol 2007; 2 : 69-78.
14Ghoreschi K, Weigert C, Rocken M. Immunopathogenesis of T-cells in psoriasis. Clin Dermatol 2007; 25 :574-580.
15Brysk M, Selvanayagam P, Arany I, Brysk H, Tyring S, Rajaraman S. Induction of apoptotic nuclei by interferon-g and by predesquamin in cultured keratinocytes. J Interferon Cytokine Res 1995; 15 :1029-1035.
16Arican O, Aral M, Sasmaz S, Ciragil P. Serum levels of TNF-α, IFN-g, IL-6, IL-8, IL-12, IL-17,and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm 2005; 273-279.
17Abdel-Hamid MF, Aly DG, Saad NE, Emad HM, Ayoub DF. Serum levels of interleukin-8, tumor necrosis factor-alpha and gamma interferon in Egyptian psoriatic patients and correlation with disease severity. J Dermatol 2011; 38 :442-446.
18Szegedi A, Aleksza M, Gonda A, Irinyi B, Sipka S, Hunyadi J, et al. Elevated rate of T helper1 lymphocytes and serum IFN-g levels in psoriatic patients. Immunol Lett 2003; 86 :277-280.
19Hong K, Chu A, Lúdviksson B, Berg E, Ehrhadt R. IL-12 independently of IFN-gamma plays a crucial role in the pathogenesis of a murine psoriasis like skin disorder. J mmunol 1999; 162 :7480-7491.
20Abdallah MA, Abdel-Hamid MF, Kotb AM, Mabrouk EA. Serum interferon-gamma is a psoriasis severity and prognostic marker. Cutis 2009; 84 :163-168.
21Almakhzangy I, Gaballa A. Serum level of IL-17, IL-22, IFN-g in patients with psoriasis. Egypt Dermatol Online J 2009; 5 :4.
22Griffiths CE. The immunological basis of psoriasis. J Eur Acad Dermatol Venereol 2003; 17 :1-5.