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Cellular Immune Response in Patients with Chronic Plaque Type Psoriasis: Evaluation of Serum Neopterin, Procalcitonin, Anti-Streptolysin O and C Reactive Protein LevelsYaşar Ibrahimbaş1, Mualla Polat1*, Erdinç Serin2 and Ali Haydar Parlak1

1Abant Izzet Baysal University, Izzet Baysal Medical Faculty, Department of Dermatology, Bolu, Turkey2Abant Izzet Baysal University, Izzet Baysal Medical Faculty, Department of Biochemistry, Bolu, Turkey

Keywords: Psoriasis; Antistreptolysin O; C reactive protein;Procalcitonin; Neopterin

IntroductionPsoriasis is a common chronic inflammatory dermatose that shows

exacerbations and remission attacks. However, the etiopathogenesis of the disease has not yet been exactly explained. It is concluded that environmental factors including β hemolytic streptococcus infections and multiple genetic components may be responsible for the pathogenesis of the disease [1-4].

C-reactive protein (CRP) has special importance for psoriasisdue to its relation with cytokines which are responsible for skin inflammation [5]. Neopterin is a marker in aromatic pteridin group and determines the activities of monocyte and macrophage system [6]. Although several studies showed that CD4+ T cells were important in the pathogenesis of psoriasis, the studies on neopterin which is the non-specific marker of the activation of cellular immunity are not adequate [1,3,6,7]. Procalcitonin (PCT) is a prohormone and converts into calcitonin. It is accepted as a specific marker of bacterial infections [8]. Antistreptolysin O (ASO) is a non-specific antibody for streptococcal infections and its level changes according to the level of streptococcus toxin and the number of organism in the body [9,10].

We aimed to determine the roles of streptococcal infections and cellular immune response in the etiopathogenesis of chronic plaque type psoriasis via using biochemical markers such as ASO, CRP, neopterin and PCT.

Material and MethodsForty patients who had chronic plaque psoriasis with

*Corresponding author: Mualla Polat, Izzet Baysal Medical Faculty, Department of Dermatology, 14280 Golkoy – Bolu, Turkey, Tel: +90 374 2534656; E-mail: polatmualla@gmail.com

Received September 14, 2010; Accepted November 03, 2010; Published November 08, 2010

Citation: Ibrahimbaş Y, Polat M, Serin E, Parlak AH (2010) Cellular Immune Response in Patients with Chronic Plaque Type Psoriasis: Evaluation of Serum Neopterin, Procalcitonin, Anti-Streptolysin O and C Reactive Protein Levels. J Clin Exp Dermatol Res 1:107. doi:10.4172/2155-9554.1000107

Copyright: © 2010 Ibrahimbaş Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

exacerbations in their and 40 healthy volunteers without any known dermatologic or systemic disease and family history of psoriasis were included in the study between July 2008 and February 2009. The lesions in the patients who stated that the number of their lesions increased more than twice within the last three weeks were accepted as exacerbations. The patient’s exclusion criteria were as follows: patients younger than 18 years of age; patients with palmoplantar or guttate psoriasis; usage of immunosuppressive drugs; presence of immunosuppressive disease; apodeictic, upper respiratory tract, urinary tract, lung, skin infections or connective tissue diseases (SLE, RA, FMF etc.); acute or chronic systemic inflammatory diseases; and taking systemic treatment of psoriasis in which ASO, CRP, neopterin and PCT could be elevated. All patients signed an informed consent form and the study was approved by institutional review board.

After recording demographic and clinical characteristics, punch

AbstractBackground: Psoriasis is characterized by T-cell mediated hyperproliferation of keratinocytes initiated by antigen-

presenting cells on the skin. Environmental factors including β hemolytic streptococcus infections and multiple genetic components may be responsible for the pathogenesis of the disease. However the antigen which initiates the immunologic reactions has not yet been known. We aimed to evaluate the relationship between streptococcal as well as other bacterial infections and psoriasis via measurement of some infection markers.

Materials and methods: The study included 40 patients with exacerbations of chronic plaque type psoriasis lesions and 40 healthy individuals. Disease activity in study group was determined according to the score of psoriasis area and severity index. Antistreptolysin O, C-reactive protein, procalcitonin and neopterin levels of patients with psoriasis were compared to those of control subjects.

Results: The levels of procalcitonin (p=0.002) and neopterin (p=0.001) in patients with psoriasis were significantly higher than those in control subjects. Additionally, there was significant correlation between psoriasis area and severity index scores and neopterin (p< 0.001) as well as C-reactive protein (p=0.006) levels. However ASO levels in patients with psoriasis did not differ significantly from those in control subjects (p=0.86).

Conclusions: Significant increased levels of serum procalcitonin during exacerbation period of chronic plaque type psoriasis may be resulted from the presence of a bacterial antigenic stimulus and significant elevated levels of neopterin may indicate elevated cellular immune system activity following bacterial antigenic stimulation. However, absence of significant elevated antistreptolysin O levels indicates the possible role of bacterial infections in the pathogenesis of psoriasis rather than streptococcal infections.

Citation: Ibrahimbaş Y, Polat M, Serin E, Parlak AH (2010) Cellular Immune Response in Patients with Chronic Plaque Type Psoriasis: Evaluation of Serum Neopterin, Procalcitonin, Anti-Streptolysin O and C Reactive Protein Levels. J Clin Exp Dermatol Res 1:107. doi:10.4172/2155-9554.1000107

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biopsy was applied to all patients and diagnosis of psoriasis was confirmed with histopathologic evaluation. Disease activity was determined according to the score of psoriasis area and severity index (PASI). Blood samples of the study and control groups were taken in the morning hours and ASO as well as CRP values were studied immediately. For the evaluation of PCT and neopterin, serums were kept at -70°C until the day on which they were studied. Just before the analysis, frozen samples were defrosted and studied.

The levels of serum ASO and CRP were measured by nephelometric method (BN prospec, DadeBehring Marburg, Germany). Serum PCT levels were measured using the Kryptor Brahms sensitive procalcitonin reagents on the fully automated random-access immunoassay system (Kryptor B∙R∙A∙H∙M∙S System Hennigsdorf, Germany).

Micro ELISA device with DRG neopterin ELISA enzymimmunoassay kit (Instruments GmbH, Germany) were used to measure neopterin levels and levels below 10 nmol/L were accepted as normal.

For statistical analysis of the data, packaged software called ″SPSS (Statistical Package for Social Sciences) for Windows 16.0″ was used. Descriptive statistics (mean and standard deviation) were computed. Continuous variables were compared with student t test and categorical variables were compared with chi square test. The relationship among neopterin, ASO, CRP and PCT was evaluated by means of Pearson correlation test. A p value less than 0.05 was accepted as statistically significant.

ResultsThe clinical characteristics and laboratory parameters of the study

and control groups are given in Table 1. According to the baseline characteristics of the analyzed patients, the difference between the two groups was not significant with regards to the age (p=0.16) and gender (p=0.82). The mean PASI score was 8.5 ± 6 in the study group and its mean level in male and female patients was 9.35 ± 6.4 and 7.08 ± 5.06, respectively (p=0.264).

The plasma levels of ASO in patients with psoriasis did not differ significantly from those in control subjects (p=0.86). CRP levels tended to be high in patients with psoriasis without showing and statistical significance (p=0.058). However PCT (p=0.002) and neopterin (p=0.001) levels of patients with psoriasis were significantly higher than those of control subjects (Figure 1). Additionally PASI score significantly correlated with CRP (p=0.006) and neopterin (p<0.001) (Figure 2). There were no correlations between PASI scores and ASO, as well as PCT (Table 2).

DiscussionPsoriasis has been accepted as a multi-factorial disease with

genetic susceptibility. The lesions in psoriasis develop secondary to T-cell mediated hyperproliferation of keratinocytes which is induced by antigen-presenting cells on the skin [11]. Although the immunogen that initiates immunologic events in psoriasis is still unknown, some

hypotheses such as molecular resemblance between streptococcal M proteins and human keratin 6 and 17 structures and aberrant self-presentation of cutaneous proteins have been asserted [1,2].

Peripheral blood lymphocyte response against Group A streptococcal immunogen increases in patients with guttate and chronic plaque type psoriasis [12-16] and the relationship between acute β hemolytic streptococcus infections and guttate psoriasis has been recently reported in patients with chronic plaque type psoriasis [16,18,19,20]. Saxena and Dogra [17] treated 30 patients successfully by using long term therapy with benzathine penicillin

Study (n=40) Control (n=40) P valueAge (years) 39.8±13.9 39.28±11.8 0.16Female Gender 15 (37.5 %) 17 (42.5 %) 0.82PASI 8.5±6 - -ASO (IU/mL) 165±120 134±78 0.86CRP (mg/L) 7.54±10.8 4.12±2.5 0.058PCT (ng/ml) 0.31±0.15 0.2±0.18 0.002Neopterin (nmol/L) 2.08±0.74 1.58±0.57 0.001

Table 1: Comparison of clinical and laboratory parameters between study and control groups.

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Figure 2: Correlation of PASI scores with Neopterin (A) and CRP (B) levels.

Table 2: Correlation of PASI score with ASO, CRP, PCT and Neopterin in patients with psoriasis.

PASI Correlation coefficient P valueASO (IU/mL) - 0.179 0.27CRP (mg/L) 0.429 0.006PCT (ng/ml) - 0.178 0.271Neopterin (nmol/L) 0.534 < 0.001

Figure 1: Graphics of ASO (A), CRP (B), neopterin (C) and procalcitonin (D) levels in study and control groups. Each box represents mean ± standart deviation.

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Citation: Ibrahimbaş Y, Polat M, Serin E, Parlak AH (2010) Cellular Immune Response in Patients with Chronic Plaque Type Psoriasis: Evaluation of Serum Neopterin, Procalcitonin, Anti-Streptolysin O and C Reactive Protein Levels. J Clin Exp Dermatol Res 1:107. doi:10.4172/2155-9554.1000107

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and concluded that continuous sub clinical streptococcal infections might be responsible for chronic plaque type psoriasis. Gudjonsson et al. [2] showed that patients with chronic plaque type psoriasis had more throat infections than healthy subjects and β-hemolytic streptococcus (M protein-positive streptococcus) which takes place in Groups A, C and G was more prevalent in throat cultures of these patients. They also reported that there was an apparent increase in the psoriatic lesions within four days after beginning of throat ache.

In the present study, ASO levels did not differ between study and control groups. In addition, there was no significant correlation between PASI score and ASO levels. Therefore we conclude that the patients with chronic psoriasis do not have laboratory signs of streptococcal infection. However it does not rule out the possible role of streptococcal infection in the etiology of psoriasis.

CRP is an acute phase reactant and it may increase in all kind of infectious and tissue damage processes [21, 22]. Rocha-Pereira et al.

[23] reported that CRP level was high in 97 to 100% of patients with moderate to severe acute psoriasis. They also found that CRP levels were significantly higher in patients with active psoriasis lesions than those in patients who were not in active period. Chodorowska et al. [5] showed that the levels of α2-makroglobulin and CRP were significantly elevated in patients with active phase psoriasis than those in inactive phase patients. Similarly, CRP levels tended to be high in patients with chronic psoriasis than those in control subjects in the present study. Coimbra et al. [24] reported similar correlation between CRP and severity of the disease. In the present study, CRP levels tended to be high in patients with chronic psoriasis than those in control subjects. Additionally, CRP levels significantly correlated with PASI scores.

The key role of PCT after the inflammation has not yet been explained clearly. CRP generally increases in bacterial, viral and autoimmune diseases. However PCT is more sensitive and specific than other acute phase reactans including CRP, IL–6 and TNF-α for identification of bacterial infections [25,26]. On the other hand, it was concluded that CRP was more sensitive and specific than serum PCT for non-specific inflammation [26]. PCT is accepted as a specific marker of the bacterial infections which are responsible for the etiology of guttate psoriasis. PCT is an important survey issue in chronic plaque type psoriasis. Although we have found increased levels of PCT in patients indicating bacterial infection, it was not correlated with the PASI score. This difference can be based on the different kinetics and profiles of CRP and PCT. The kinetics of CRP is slower than that of PCT. Additionally, delayed admission of the patients to the hospital and decreasing the levels of PCT except in acute exacerbations may play a role.

Neopterin is a non-specific marker that shows the activation of cellular immune system. It is considered that the response of cellular immune system which is formed against immunogen plays an important role in psoriasis. Neopterin is formed by the activation of T cells which originate from human monocytes and macrophages by stimulation of IFN-γ. There are some studies in the literature in which serum neopterin levels were researched and compared to PASI values. Fuchs et al. [27] showed that the neopterin in urine and blood increased in very few patients and decreased after the patients get recovered. Harland et al. [28] found that the ratio of neopterin to creatinine was significantly higher in 40 patients with psoriasis than those in control subjects and decreased after treatment. There was significant correlation between the neopterin levels as well as ratio of neopterin to creatinin before the treatment and PASI scores.

Sanchez-Regana et al. [29] found that the levels of serum neopterin significantly elevated in patients with psoriasis than those in control subjects and decreased after treatment. They also indicated that the serum neopterin levels might be an indicator of the psoriasis activity and used to measure the efficiency of the treatment.

Some virus infections, various cardiovascular risk factors, ethnic origin and body mass index of the patients can also influence the levels of neopterin [30]. Moreover, serum neopterin levels were found to be higher in patients with some skin disorders such as acute and chronic spontaneous urticaria, atopic dermatitis and lichen planus. However it is not necessary to be related with concomitant infectious disease [6,31,31]. Our study demonstrated that serum neopterin levels eleveted in psoriais. Therefore high neopterin levels may indicate possible immune system activity and clinically associated infections.

In conclusion, we have shown increased activation of cellular immune system by means of neopterin, evidence of possible bacterial antigenic stimulation by means of PCT and absence of recent streptococcal infection by means of ASO measurement. These findings indicate the possible role of bacterial infection rather than the streptococcal infections in the pathogenesis of psoriasis. However the small number of the patients in study and control groups is the main limitation of the present study. It would be interesting to include a control group with stable psoriasis and compared it with control subjects as well as with patients who had psoriasis with exacerbations in their lesions. Neopterin levels also can show some differences between the age groups. However the patients could not be separated according to their ages due to the small number of patients in the present study. Additional studies with a large number of patients are needed to validate the exact pathophysiologic relationship between the psoriasis and bacterial infections.

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Citation: Ibrahimbaş Y, Polat M, Serin E, Parlak AH (2010) Cellular Immune Response in Patients with Chronic Plaque Type Psoriasis: Evaluation of Serum Neopterin, Procalcitonin, Anti-Streptolysin O and C Reactive Protein Levels. J Clin Exp Dermatol Res 1:107. doi:10.4172/2155-9554.1000107

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