ORIGINAL ARTICLE Year : 2021  |  Volume : 41  |  Issue : 2  |  Page : 71-74

Assessment of serum amyloid A level and the severity of atopic dermatitis

Fathia M Khattab1, Hoda A Ibraheem2
1 Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission09-Jan-2020Date of Acceptance30-Jul-2020Date of Web Publication30-Jun-2021

Correspondence Address:
MD Fathia M Khattab
Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig University, 44519
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ejdv.ejdv_27_19

Background Serum amyloid A (SAA) is an acute-phase protein that activates immune cells and induces cytokines and chemokine. SAA levels in the blood have been reported to be elevated in case of inflammation, infections, neoplasia, and tissue injury. This study measured the SAA in patients with atopic dermatitis (AD) and evaluated the association between the severity of AD and their values.
Patients and methods A total of 52 patients with AD (22 males and 30 females) were involved in our study. Subjects were characterized as having atopic eczema (eAD; n=25) extrinsic type AD or nonatopic (iAD; n=27) intrinsic AD by serum immunoglobulin E level. Serum soluble IL-2R (IL-2R) and SAA levels were measured.
Results The serum SAA levels was detectable in all patients with AD, showing significantly higher levels (P=0.026) in the patients with eAD (207 pg/ml; 95% confidence interval: 172–242 pg/ml) compared with those with iAD (144 pg/ml; 95% confidence interval: 116–178 pg/ml). The serum SAA levels were significantly correlated with eosinophil counts and sIL-2R levels and showed a tendency to correlate with SCORAD index and serum immunoglobulin E levels.
Conclusion These results suggest SAA level as a parameter of AD activity and may support its possible role in the pathogenesis of AD.

Keywords: atopic dermatitis, SCORAD index, serum soluble IL-2R

How to cite this article:
Khattab FM, Ibraheem HA. Assessment of serum amyloid A level and the severity of atopic dermatitis. Egypt J Dermatol Venerol 2021;41:71-4
How to cite this URL:
Khattab FM, Ibraheem HA. Assessment of serum amyloid A level and the severity of atopic dermatitis. Egypt J Dermatol Venerol [serial online] 2021 [cited 2021 Jul 1];41:71-4. Available from: http://www.ejdv.eg.net/text.asp?2021/41/2/71/319626   Introduction 

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by eczematous skin lesions and intense pruritus [1]. AD is characterized by allergies characterized by a T-helper cell type 2 (Th2). It is a highly inflammatory disease of the skin and highly expresses Th2 cytokines [2]. Interleukin (IL)-2 initiates and develops the immune response through binding to the interleukin-2 receptor (IL-2R) on T cells.

Levels of soluble IL-2R (sIL-2R) may be estimated as a sign of T-cell activation in the serum of patients having many disorders involving aberrant immune activation and serum levels of soluble interleukin (IL)-2 receptor (sIL-2R), which reflect disease severity in patients with AD [3]. There is an increased eosinophil number in peripheral blood and elevated serum levels of immunoglobulin (Ig)E [4].

Serum amyloid A (SAA) is an evolutionary conserved approximately 12-kDa acute-phase protein. Although SAA is mainly produced in the liver, it can also be produced by macrophages, neutrophils, and smooth muscle cells [5]. In chronic inflammatory diseases, such as rheumatoid arthritis, metabolic syndrome, and atherosclerosis, prolonged elevation of SAA may contribute to tissue damage and degradation [6]. Moreover, SAA is known to activate immune cells and induce cytokines and chemokines [7].

SAA is an apolipoprotein that is a component of high-density lipoprotein particles in the blood and is increased in the case of inflammation, infections, neoplasia, and tissue injury [8].

So, the aim of the present work was the estimation of the serum levels of SAA as immunological factors in patients with AD and to test the correlation between these serum levels and SCORAD index.

  Patients and methods 

From February 2019 to February 2020, 52 patients with AD were recruited from the Department of Dermatology Zagazig University, after obtaining the approval of the research ethics committee. The diagnosis of AD was based on the Hanifin and Rajka criteria [9]. The severity of AD was assessed using the SCORAD Index of Dermatitis (SCORAD) [10]. The topic history, family history, and allergic medication were examined. Eosinophil counts of peripheral blood, serum IgE levels, and serum soluble IL‐2 receptor (sIL‐2 R) levels were also measured as markers for AD activity [11].

Allergy test

Serum IgE level and peripheral blood eosinophil count were measured as a basic allergy test. The reported mean values of total serum IgE value less than 150 kU/l have been used for an indication of endogenous AD [12].

Serum biomarker measurement

Enzyme-linked immunosorbent assay (ELISA): SAA levels in blood were quantified using a Human Serum Amyloid A ELISA kit (LSBio, Seattle, Washington State, USA). Optical densities were measured at 450 nm using a Bio-Rad Model 550 microplate reader (Bio-Rad Laboratories, Hercules, California, USA). The concentrations were calculated from the standard curve generated by a four-parameter curve-fitting program.The levels of sIL‐2 R were assessed with a commercially available enzyme-linked immunosorbent assay (ELISA; Diaclone, Besancon Cedex, France), and its normal range was 124–466 U/ml.

Statistical analysis

It was performed using the IBM SPSS ver. 22.0 (IBM Co., Armonk, New York, USA). The Mann–Whitney U-test or the Spearman rank correlation was used to comparing the results. Results were considered significant at P less than 0.05.

  Results 

A total of 52 patients with AD (22 males and 30 females) were involved in our study. Subjects were characterized as having atopic eczema (eAD; n=25) extrinsic type AD or nonatopic (iAD; n=27) intrinsic AD by serum Ig E level. Their mean age was 28.0 years (range: 13–43 years), and their mean disease duration was 14.4 years (range: 2–25 years). The mean age and sex of the two AD groups were not different ([Table 1]). The SCORAD index was significantly higher in the eAD group than in the iAD group (37.67±13.29 vs 20.87±9.16, P<0.001) ([Table 1]).

Eosinophil counts, serum IgE levels, and serum sIL-2R levels were 871/lL [95% confidence interval (CI): 624–1118/ll], 9124 IU/ml (95% CI: 6320–11928 IU/ml), and 852U/ml (95% CI: 654–1049 U/ml), respectively.

SCORAD index correlated significantly with eosinophil counts (r=0.54; P=0.007), IgE levels (r=0.42; P=0.034), and sIL-2R levels (r=0.64; P=0.002) ([Table 1]). Eosinophil counts correlated with sIL-2R (r=0.45; P=0.023), whereas eosinophil counts did not show a significant correlation with serum IgE levels (r=0.35; P=0.077). Serum IgE levels did not correlate with sIL-2R levels (r=0.13; P=0.532).

SAA was detectable in all patients with AD and showed significantly higher levels (P=0.026) in the patients with eAD (207 pg/ml; 95% CI: 172–242 pg/ml) compared with iAD (144 pg/ml; 95% CI: 116–178 pg/ml) ([Figure 1]).

SAA levels correlated significantly with eosinophil counts (r=0.47; P=0.019) and sIL-2R levels (r=0.48; P=0.016) and showed a tendency to correlate with SCORAD index (r=0.39; P=0.0516) and serum IgE levels (r=0.38; P=0.060) ([Table 2]).

Table 2 Correlation among SCORAD index and other parameters by the Spearman rank correlation

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  Discussion 

In this study, SAA levels were significantly higher in patients with eAD than in iAD. Furthermore, SAA levels correlated with the clinical activities, suggesting that SAA production is increased in patients with eAD and that measurement of SAA levels is an objective laboratory parametter for AD activity.

AD is a hypersensitivity reaction caused by immunological mechanisms mediated by IgE antibodies [2]. IgE is essential for the initiation and spread of the inflammatory cascade and allergic reactions [3].

To our knowledge, this is the first study to measure SAA in AD and correlation with IgE and clinical activity of the disease. In this study, we found that serum SAA was detectable in all patients with AD and showed significantly higher levels in the patients with eAD compared with those with iAD. Therefore, measurement of SAA levels is an objective laboratory parameter for AD activity.

SAA levels correlated significantly with eosinophil counts and sIL-2R levels and showed a tendency to correlate with SCORAD index and serum IgE levels.

SAA, an endogenous mediator, induces innate immune cytokine production, neutrophilia, and polarizes Th17 responses to innocuous inhaled antigens [12]. It reported that SAA stimulates the extracellular toll-like receptor 2 (TLR2) [13]. SAA induces interferon-γ production in synergy with IL-12 but it also induces IL-13, a Th2 cytokine, in synergy with IL-2 in the absence of interferon-γ [14]. Therefore, it has been suggested that SAA has diverse abilities to cross-regulate Th1/Th2 derivation and function depending on the experimental conditions [15].

The pharmacologic antagonism of the IL-1 receptor prevents IL-17 production in vitro, and IL-1 receptor-deficient (IL-1R) mice do not undergo Th17 polarization in response to SAA-inducing exposures that promote allergic sensitization to ovalbumin or combined administration of SAA and ovalbumin [16]. Finally, SAA increases Th2 cytokine production and serum IgE levels and induces eosinophil recruitment, which suggests that SAA may contribute to the pathogenesis of allergic reaction [17].

Suzuki et al. [18] examined SAA levels in the blood of patients with AD and cutaneous T‐cell lymphoma (CTCL). SAA levels in sera of patients with AD, those of patients with CTCL, and those of healthy controls were not significantly different. In patients with AD, however, SAA levels positively correlated with the number of eosinophils in peripheral blood, and patients with AD without topical steroid treatment and patients with CTCL without narrowband ultraviolet B therapy showed increased levels of SAA, which suggested that SAA levels may easily fluctuate with treatment.

In psoriatic skin, keratinocytes contribute to the pathogenesis via the production of A-SAA and that its autocrine response maintains a cutaneous Th17-polarized inflammation [19].

The association between SAA and urticarial was investigated and there was an association between SAA levels and urticaria. Higher SAA levels were associated with AU and more severe CU [20].

The limit of this study was a low number of patients. In the future, we will need a large-scale prospective randomized study and histopathological examination to determine the correlation between SAA and SIL-2R.

  Conclusion 

Serum SAA reflects the severity of AD, suggesting that SAA may play an important role in understanding the pathophysiology of AD, and prognosis. Thus, SAA and sIL-2R are probable to mediate early allergic response after allergic exposure and attribute to the growth of Th-dominant inflammation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest‏.

 

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  [Figure 1]
 
 
  [Table 1], [Table 2]