Egyptian Rheumatology and Rehabilitation

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 46  |  Issue : 2  |  Page : 108--112

Relation of ischemia-modified albumin to disease manifestations and activity in Egyptian patients with Behҫet’s disease


Nermeen A Fouad1, Tarek I Ahmed2, Olfat G Shaker3, Omayma O Abdelaleem4,  
1 Department of Rheumatology and Rehabilitation, Faculty of Medicine, Fayoum University, Fayoum, Egypt
2 Department of Internal Medicine, Faculty of Medicine, Fayoum University, Fayoum, Egypt
3 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt
4 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Fayoum, Egypt

Correspondence Address:
Nermeen A Fouad
Department of Rheumatology, Faculty of Medicine, Fayoum University, Fayoum, 63511
Egypt

Abstract

Aim of work To determine level of ischemia-modified albumin (IMA) in patients with Behçet’s disease (BD) and to assess its role in disease manifestations and activity. Patients and methods The study included 48 patients with BD and 38 matched controls. Disease activity was estimated by the BD current activity form. Serum IMA was measured. Results Mean age of the patients was 33.8±7.9 years. There were 42 males and six females, and the disease duration was 52.9±48.8 months. The serum IMA level was significantly increased in the patients with BD (50.9±12.9 U/ml) compared with the control (7.76±1.6 U/ml) (P<0.001). There was a statistically significant association between IMA level and disease activity, with high mean IMA level among active cases (P=0.01). There was no statistically significant association between IMA level and any of other clinical characteristics in patients with BD. Sensitivity and specificity test for IMA level in detection of cases illustrated accuracy of 98.5% with sensitivity 95.8% and specificity 78.9% at cutoff value of 9.4 U/ml. Conclusion There is growing evidence indicating the role of oxidative stress in BD. IMA is accepted as an essential marker of oxidative stress in patients with BD. It has a potential diagnostic value for the detection of the disease. Furthermore, it correlates with the disease activity.



How to cite this article:
Fouad NA, Ahmed TI, Shaker OG, Abdelaleem OO. Relation of ischemia-modified albumin to disease manifestations and activity in Egyptian patients with Behҫet’s disease.Egypt Rheumatol Rehabil 2019;46:108-112


How to cite this URL:
Fouad NA, Ahmed TI, Shaker OG, Abdelaleem OO. Relation of ischemia-modified albumin to disease manifestations and activity in Egyptian patients with Behҫet’s disease. Egypt Rheumatol Rehabil [serial online] 2019 [cited 2020 Mar 30 ];46:108-112
Available from: http://www.err.eg.net/text.asp?2019/46/2/108/256503


Full Text



 Introduction



Behçet’s disease (BD) is a recurring inflammatory multisystem disease; it is characterized by recurrent oral aphthosis, genital ulceration, ocular and variable skin is frequently associated with vascular thrombosis and formation of arterial aneurysms [1]. Male individuals are more frequently affected compared with female individuals, and it is more common in the second to fourth decade of life [2].

The etiology, pathogenesis, and mechanisms that underlie vascular disease occurring in BD are unknown. Alterations of the immunoregulatory system have been suggested to play an important role; many proinflammatory cytokines and B-cell activation have been involved in the pathogenesis of the disease [3],[4]. Endothelial dysfunction and disturbed neutrophil functions, such as phagocytosis, chemotaxis, and generation of reactive oxygen species (ROS) have been suggested to be factors in the pathophysiology and etiology of BD. Overproduction of ROS with decreased level of antioxidant defense system was found to occur in BD, leading to increase of oxidative stress [5].

Ischemia-modified albumin (IMA) is recently accepted as a biomarker of ischemia and oxidative stress. It is broadly studied in many types of ischemic diseases [6],[7],[8]. In addition, its level is found to be elevated in diseases accompanied by vascular endothelial cell dysfunction [9].

The aim of this study is to determine levels of IMA in patients with BD and to assess its role in disease manifestations and activity.

 Patients and methods



A total of 48 patients with BD and 38 age-matched and sex-matched healthy volunteers as controls were recruited in the study. BD diagnosis was made based on The International Criteria for Behçet’s Disease [10].

The study was approved by the Local Research Ethical Committee of Fayoum University and conforms to the 1995 Declaration of Helsinki. After obtaining informed consent from all of the study participants, complete systemic and ophthalmologic examinations were done for all patients to define systemic and ophthalmic involvement. The current activity form of Behçet’s disease was assessed [11]. Patients having any systemic disease were excluded from the study.

Serum IMA was measured quantitatively using the Human IMA ELISA Kit (Sun Long Biotech Co. Ltd) according to the manufacturer’s protocol. To obtain serum, blood samples were centrifuged at 3000 rpm for 10 min and stored at −80°C. IMA levels were detected by adding 40 µl of sample dilution buffer and 10 µl of sample (dilution factor is 5) in sample wells; empty well was left as blank control. Closure plate membrane was used to cover wells to be incubated at 37°C for 30 min. According to the manufacturer’s protocol, dilution of the concentrated buffer with distilled water washing was done. The plate was incubated and washed after adding 50 µl HRP-conjugate reagents to each well excluding the blank control well. Then, 50 µl of chromogen solution A and 50 µl of chromogen solution B were then added to each well for 15 min in the dark. The color reaction was terminated by adding 50 µl of stop solution to each well to terminate the reaction. By comparing the absorbance values at 450 nm using a Microtiter Plate Reader, IMA concentrations were measured.

Statistical analysis

Data were analyzed by statistical package of social science software, version 18, in Windows 7 (Milton, QLD, Australia). Simple descriptive analyses in the form of numbers and percentages were used for qualitative data, and arithmetic means as central tendency measurement and standard deviations as measure of dispersion were used for quantitative parametric data. Quantitative data included in the study was first tested for normality by one-sample Kolmogorov–Smirnov test in each study group, and then inferential statistic tests were selected. For quantitative parametric data, independent Student’s t test was used for comparing measures of two independent groups of quantitative data. For qualitative data, χ2 test was used to compare two or more than two qualitative groups. Bivariate Pearson’s correlation test was used to test association between variables. Sensitivity and specificity of IMA level in diagnosis of Behçet’s disease with receiver operating characteristic (ROC) curve. The P value less than or equal to 0.05 was considered as the cut-off value for significance.

 Results



The mean age of study group was 33.8±7.9 years, with 87.5% were males and 12.5% were females. The patients’ characteristics are presented in [Table 1]. The serum level of IMA was significantly increased in the group of patients with BD (50.9±12.9 U/ml) compared with the control group (7.76±1.6 U/ml) (P<0.001) ([Figure 1]).{Table 1}{Figure 1}

There was a statistically significant association between IMA level and disease activity, with high mean IMA level among active cases (P=0.01). There was no statistically significant association between IMA level and any of other clinical characteristics of patients with BD ([Table 2]). Moreover, there was no statistically significant correlation (P value more than 0.05) between IMA level and any of age of the patients or duration of the disease (r=0.03, P=0.9 and r=−0.40, P=0.06, respectively), which indicated that there was no effect of these variables on IMA level.{Table 2}

Sensitivity and specificity test for IMA level in detection of cases illustrated accuracy of 98.5% with sensitivity 95.8% and specificity 78.9% at cutoff value of 9.4 U/ml ([Figure 2]).{Figure 2}

 Discussion



BD is a systemic relapsing inflammatory disease; vascular involvement commonly occurs and predisposes to thrombosis [12]. Oxidative stress plays a major role in endothelial dysfunction and vascular injury [13],[14].

ROS and lipid peroxides have been involved in the pathogenesis of various immune-mediated diseases [15],[16]. IMA has been studied in diseases associated with oxidative stress and endothelial dysfunction [9],[17],[18]. Moreover, it is considered as a biomarker of ischemia, oxidative stress, and endothelial dysfunction [9],[19].

Levels of IMA are increased as a result of oxidative stress induced during inflammation. As a marker of oxidative stress, IMA is assumed to be connected to the pathogenesis of BD [20]. It is a metabolic variant of the protein which is generated during acute ischemic conditions owing to a free radical damage, resulting in decrease in the albumin-binding capacity for transition metals, such as cobalt, copper, and nickel [19],[21]. The binding capacity of the albumin to transition metals can also be modified as a result of oxidative stress [22].In the present study, IMA level was detected, and the association between it and specific clinical features and disease activity of BD was investigated, and it was found that level of serum IMA was significantly increased in the patients with BD compared with the control. In addition, it significantly correlated with Behçet disease current activity form.

In accordance with the current study, Kılıç et al. [23] found that the IMA values of patients with BD during the active phase of the disease were significant as compared with the inactive phase and with the control group. Moreover, a study by Ozyazgan et al. [20] showed higher level of IMA in patients with BD during the active state of the disease.

Capkın et al. [18] concluded that IMA is a marker for patients with BD with vascular affection. They found that IMA levels were statistically significantly higher in patients with BD with vascular manifestations. However, the present study did not confirm this association.

 Conclusion



There is growing evidence indicating the role of oxidative stress in BD. IMA is accepted as an essential marker of oxidative stress in patients with BD. It has a potential diagnostic value for the detection of the disease. Furthermore, it correlates with the disease activity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Mahr A, Belarbi L, Wechsler B, Jeanneret D, Dhote R, Fain O et al. Population based prevalence study of Behcet’s disease differences by ethnic origin and low variation by age at immigration. Arthritis Rheum 2008; 58:3951–3959.
2Khabbazi A, Rashtchizadeh N, Ghorbanihaghjo A, Hajialiloo M, Ghojazadeh M, Taei R, Kolahi S. The status of serum vitamin D in patients with active Behcet’s disease compared with controls. Int J Rheum Dis 2014; 17:430–434.
3Gheita TA, Raafat H, Khalil H, Hussein Serum H. Level of APRIL/BLyS in Behçet’s disease patients: clinical significance in uveitis and disease activity. Mod Rheumatol 2013; 23:542–546.
4Gheita TA, Gamal SM, Shaker I, El Fishawy HS, El Sisi R, Shaker OG et al. Clinical significance of serum interleukin-23 and A/G gene (rs17375018) polymorphism in Behçets disease: relation to neuro-Behçet, uveitis and disease activity. Joint Bone Spine 2015; 82:213–215.
5Taysi S, Kocer I, Memisogullari R, Kiziltunc A. Serum oxidant/antioxidant status in patients with Behçet’s disease. Ann Clin Lab Sci 2002; 32:377–382.
6Behera S, Mangaraj M, Mohapatra PC. Diagnostic efficacy of ischemia modified albumin and its correlation with lipid profile, oxidative stress in acute myocardial infarct patients on admission. Asian Pac J Trop Dis 2012; 2:62–65.
7Jena I, Mohapatra PC, Mohanty NR. Ischemia modified albumin: a biochemical marker of acute stroke. Int J Pharm Bio Sci 2016; 7:15–19.
8Gunduz A, Turedi S, Mentese A, Karahan SC, Hos G, Tatli O et al. Ischemia-modified albumin in the diagnosis of acute mesenteric ischemia: a preliminary study. Am J Emerg Med 2008; 26:202–205.
9Ozdemir M, Kivici A, Balevi A, Mevlitoğlu I, Peru C. Assessment of ischaemia-modified albumin level in patients with psoriasis. Clin Exp Dermatol 2012; 37:610–614.
10Davatchi F, Assaad-Khalil S, Calamia KT, Crook JE, Sadeghi-Abdollahi B, Schirmer M et al. The International Criteria for Behçet’s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol 2014; 28:338–347.
11Bhakta BB, Brennan P, James TE, Chamberlain MA, Noble BA, Silman AJ. Behçet’s disease: evaluation of a new instrument to measure clinical activity. Rheumatology (Oxford) 1999; 38:728–733.
12Emmi G, Silvestri E, Squatrito D, Amedei A, Niccolai E, D’Elios MM et al. Thrombosis in vasculitis: from pathogenesis to treatment. Thromb J 2015; 13:15.
13Niwa Y, Miyake S, Sakane T, Shingu M, Yokoyama M. Auto-oxidative damage in Behcet’s disease endothelial cell damage following the elevated oxygen radicals generated by stimulated neutrophils. Clin Exp Immunol 1982; 49:247–255.
14Chambers JC, Haskard DO, Kooner JS. Vascular endothelial function and oxidative stress mechanisms in patients with Behcet’s syndrome. J Am Coll Cardiol 2001; 37:517–520.
15Taysi S, Gul M, Sari RA, Akcay F, Bakan N. Serum oxidant/antioxidant status in serum of patients with systemic lupus erythematosus. Clin Chem Lab Med 2002; 40:684–688.
16Karkucak M, Capkin E, Alver A, Akyuz A, Kiris A, Ak E et al. The effect of anti-TNF agent on oxidation status in patients with ankylosing spondylitis. Clin Rheum 2010; 29:303–307.
17Aydin O, Ellidag HY, Eren E, Kurtulus F, Yaman A, Yılmaz N. Ischemia modified albumin is an indicator of oxidative stress in multiple sclerosis. Biochem Med (Zagreb) 2014; 24:383–389.
18Capkin E, Karkucak M, Kola M, Karaca A, Aydin Capkin A, Caner Karahan S. Ischemia-modified albumin (IMA): a novel marker of vascular involvement in Behçet’s disease? Joint Bone Spine 2015; 82:68–69.
19Lippi G, Montagnana M, Guidi GC. Albumin cobalt binding and ischemia modified albumin generation: An endogenous response to ischemia? Int J Cardiol 2006; 108:410–411.
20Ozyazgan S, Andican G, Erman H, Tuzcu A, Uzun H, Onal B, Ozyazgan Y. Relation of protein oxidation parameters and disease activity in patients with Behçet’s disease. Clin Lab 2013; 59:819–825.
21Eom JE, Lee E, Jeon KH, Sim J, Suh M, Jhon GJ et al. Development of an albumin copper binding (ACuB) assay to detect ischemia modified albumin. Anal Sci 2014; 30:985–990.
22Roy D, Quiles J, Gaze DC, Collinson P, Kaski JC, Baxter GF. Role of reactive oxygen species on the formation of the novel diagnostic marker ischaemia modified albumin. Heart 2006; 92:113–114.
23Kılıç S, Işık S, Hiz MM, Çakır DÜ, Türkön H, Cevizci S, Ogretmen Z. The ischemia modified albumin and mean platelet volume levels in patients with Behçet’s disease. Postepy Dermatol Alergol 2016; 33:345–348.