|Year : 2018 | Volume
| Issue : 3 | Page : 805-809
Serum interleukin-17 level in patients with ankylosing spondylitis and its relation with disease activity
Abd El-Samad I Al Hewala1, Samar G Soliman2, Manal A Saafan3, Alaa A Labeeb2, Amany M Hashish4
1 Rheumatology, Physical Medicine and Rehabilitation Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Physical Medicine and Rehabilitation Department, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
3 Biochemistry Department, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
4 Rheumatology and Rehabilitation at Ministry of Health, Menoufia, Egypt
|Date of Submission||30-Jul-2017|
|Date of Acceptance||08-Oct-2017|
|Date of Web Publication||31-Dec-2018|
Amany M Hashish
Rheumatology and Rehabilitation at Ministry of Health, Tala, Menoufia
Source of Support: None, Conflict of Interest: None
The aim of this study is to measure the level of interleukin-17 (IL-17) in the serum of patients with ankylosing spondylitis (AS) and correlating it with disease activity.
AS is a chronic inflammatory disease that affects axial joints, characterized by a diffuse stiffness, with the advanced stage producing a rigid spine from the occiput to the sacrum. IL-17 may play a role in the pathogenesis, activity, and clinical manifestations of AS. IL-17 is produced by T helper 17 cells.
Fifty patients with AS (male:female 48:2) and 20 age-matched healthy male volunteers as controls were included in this study. Patients were diagnosed as having AS according to Assessment of SpondyloArthritis International Society criteria. All were subjected to demographic data, clinical examination, and laboratory investigations including serum level of IL-17A by enzyme-linked immunosorbent assay. The results were correlated with disease activity, which was assessed by Bath Ankylosing Spondylitis Disease Activity Index and Ankylosing Spondylitis Disease Activity Score.
In our study, the serum levels of IL-17A in patients were significantly higher than those of the healthy controls (P < 0.001). There was a positive correlation between serum IL-17A and both Bath Ankylosing Spondylitis Disease Activity Index and Ankylosing Spondylitis Disease Activity Score and negative correlation between serum IL-17A and disease duration.
Serum IL-17A levels of patients with AS were significantly higher than healthy controls, and it was positively correlated with disease activity.
Keywords: ankylosing, interleukin-17, interleukin-17A, sacrum, spine, spondylitis
|How to cite this article:|
Al Hewala AE, Soliman SG, Saafan MA, Labeeb AA, Hashish AM. Serum interleukin-17 level in patients with ankylosing spondylitis and its relation with disease activity. Menoufia Med J 2018;31:805-9
|How to cite this URL:|
Al Hewala AE, Soliman SG, Saafan MA, Labeeb AA, Hashish AM. Serum interleukin-17 level in patients with ankylosing spondylitis and its relation with disease activity. Menoufia Med J [serial online] 2018 [cited 2019 Jan 22];31:805-9. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/805/248747
| Introduction|| |
Ankylosing spondylitis (AS) is a chronic inflammatory disease with unclear pathogenesis, which affects the sacroiliac joints and the spine with a progressive course. Etiopathogenesis of AS is not clearly known, but many of genetic and environmental factors have a role. Moreover, recent data have reported that elevated blood levels of proinflammatory cytokines such as interleukin (IL)-1, interferon γ, tumor necrosis factor-α, IL-6, IL-17, and IL-23 might play a role in pathogenesis. This role is supported by that disease symptoms and activity could be affected by blocking of the cytokines. High levels of serum IL-17 have been reported in AS. IL-17 is a proinflammatory cytokine released in response to invasion of extracellular pathogens for immunity, and it acts synergistically with IL-1 and tumor necrosis factor. IL-17 is produced by T-helper cells and is induced by IL-23; it acts as a potent mediator by increasing chemokine production in tissues in delayed-type reactions, finally causing damage and destruction of tissue.
The aim of our study was to measure the levels of IL-17A in the serum of patients with AS and its correlation with disease activity.
| Patients and Methods|| |
Fifty patients diagnosed as having AS and 20 healthy control patients were included in this study. They were randomly recruited from the Internal Medicine, Physical Medicine, Rheumatology, and Rehabilitation Clinic of Menoufia University Hospitals during the years 2015–2016. The study included both sexes. A total of 48 (96%) patients were males and two (4%) were females. Their ages ranged from 20 to 47 years. Their disease duration ranged from 1 to 20 years.
Patients were diagnosed as having AS according to Assessment of SpondyloArthritis International Society (ASAS) criteria.
According to disease activity, which was assessed by Bath Ankylosing Spondylitis Disease Activity Index score and Ankylosing Spondylitis Disease Activity Score (ASDAS), patients were divided into two groups: group I included patients in disease activity, with a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score more than 4, and group II included patients in remission, with a BASDAI score less than 4.
All patients and control group gave written informed consent for our study. The study was conducted according to the guidelines of Menofiya University Ethical Committee after obtaining approval from the ethical committee.
Randomization was done as listed by randomization technique in Microsoft Excel Program (Microsoft for windows, USA).
All patients were subjected to demographic data recording, history taking, and clinical examination, including general examination by examination of the pulse, temperature, blood pressure, eye, mouth, skin and nail, lymph nodes, chest, and heart. Moreover, abdominal and neurological examinations were done.
Patients were also subjected to local examination of joints; all joints of the body were examined with the routine articular physical examination that include inspection, palpation, and range of motion. Disease activity assessment was done by using BASDAI score and ASDAS.
All patients underwent complete blood count, erythrocyte sedimentation rate (ESR), rheumatoid factor, and C-reactive protein (CRP) assessment. aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT), serum urea, creatinine level, rheumatoid factor, human leukocyte antigen B27, and IL-17 in serum by enzyme-linked immunosorbent assay (ELISA) using human IL-17 ELISA Kit (Glory Science Co. Ltd, Del Rio, Texas, USA) were recorded. Moreover, radiological examination included plain radiography of sacroiliac joints and plain radiography of lumbosacral spine.
The data collected were tabulated and analyzed by statistical package for the social sciences, version 22.0, on IBM compatible computer (SPSS Inc., Chicago, Illinois, USA). Two types of statistics were done: descriptive statistics included percentage, range, mean, and SD, and analytical statistics comprised Student's t-test, Mann–Whitney U-test, and Fisher's exact test. P value of more than 0.05 was considered nonsignificant, less than 0.05 was considered significant difference, and less than 0.001 was considered highly significant difference.
| Results|| |
This study included 50 patients, with 48 (96%) males and two (4%) females. The mean age was 26.6 ± 7.1 years, ranging from 20 to 47 years.
In this study, there was nonsignificant difference between the patients' groups and between the patient and control groups regarding age and sex [Table 1].
|Table 1: Demographic data and serum interleukin-17A levels among patients and control groups|
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There was a highly significant statistical difference regarding IL-17A level in the blood between the patients' groups and patient groups versus control (P < 0.01) [Table 1].
There was a positive correlation between serum IL-17A and BASDAI and ASDAS (ESR and CRP) scores. Moreover, a negative correlation was found between serum IL-17A and disease duration in both groups [Table 2] and [Table 3].
|Table 2: Correlation between serum interleukin-17A levels and disease activity measures in patients of group I|
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|Table 3: Correlation between serum interleukin-17A levels and disease activity measures in patients of group II|
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There was a highly significant difference between patients groups regarding pain, morning stiffness [visual analogue scale (VAS)], patient global assessment (VAS), BASDAI, tender joints count, and swollen joints count (P < 0.01) and significant difference regarding CRP and ESR (P < 0.05) [Table 4].
|Table 4: Comparison between disease activity measures and patients groups|
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| Discussion|| |
AS is a chronic inflammatory disease that predominantly affects the spine and sacroiliac joints, and it is also associated with human leukocyte antigen B27. High levels of serum IL-17 have been reported in AS.
Our study included 50 patients with AS, who were divided into two groups according to disease activity score BASDAI and ASDAS, with mean age of 31.36 ± 8.06 and 28.45 ± 4.8 years, and with mean disease duration of 6 ± 4.7 and 6 ± 5.4 years for group I and group II, respectively, in addition to 20 healthy controls. The patients were diagnosed as having AS according to Assessment of SpondyloArthritis International Society (ASAS) criteria.
The present study shows presence of high levels of IL-17A in serum of patients with AS more than controls and also significant difference between the patients groups and between patient and control groups regarding IL-17A levels in the blood.
This comes in agreement with Liu et al. who revealed a strong correlation between elevated serum IL-17 serum levels and the development of AS. Moreover, serum IL-17A levels of patients were significantly higher than those of the healthy controls. Therefore, IL-17A could be used as a marker for diagnosis and assessment of treatment outcomes in patients with AS.
In the same line, Chen et al. performed a study on 49 patients with AS and 25 healthy control patients. The serum IL-17 levels by ELISA, CRP, ESR, BASDAI, BASFI, and Bath Ankylosing Spondylitis Patient Global Score were measured, and they reported higher serum levels of IL-17A in patients with AS compared with normal control patients.
Moreover, Londono et al., showed high levels of IL-17A in patients with SpA when compared with healthy patients.
In agreement with our results, Romero-Sanchez et al. reported higher serum levels of IL-17A in patients with SpA than healthy controls, but there were no differences among the subtypes of SpA.
Mei et al. and Wang et al. reported that IL-17A levels in serum when measured in patients with AS were significantly higher than those in healthy controls. Moreover, Wendling et al. found that the levels of IL-17A were elevated in established and active patients with AS, when compared with the normal control patients.
Another study that partially supported our results was conducted by Taylan et al. who reported that certain cytokines that were measured by ELISA including IL-17A were high in the serum of patients with AS when compared with healthy control patients (P < 0.05), but theses cytokines were similar between patients groups, which were divided according to activity and remission of disease.
Wendling and Toussirot reported elevated serum levels of IL-17A in patients with AS when compared with healthy patients, but no difference was found between patients when compared regarding BASDAI score as a method of activity measurement or laboratory measures of inflammation.
The present study showed positive correlation between serum IL-17 and BASDAI and ASDAS (ESR and CRP) scores in both patient groups.
This comes in agreement with Chen et al. who reported that in the patients with AS, the BASDAI scores had positive correlation with the serum IL-17A and with other activity measures such as the BASFI, Bath Ankylosing Spondylitis Patient Global Score, and parameters related to physical mobility.
In contrast, Muntean et al. reported that IL-17A levels were not correlated with markers of disease activity or with functional disability, although it were elevated in patients with active disease. Moreover, Sveaas et al., who measured serum IL-17A levels of patients with AS but reported no differences between the groups, also found no significant difference between disease activity measures and inflammatory markers.
Our study showed there was a highly significance difference between the patients groups regarding activity measures [pain, morning stiffness (VAS), patient global assessment (VAS), BASDAI, tender joints count, and swollen tender joints], and significance difference between the patient groups regarding ESR and CRP.
This come in agreement with Yildrim et al. who reported a highly significant difference between the groups regarding activity signs [pain, morning stiffness (VAS)], patient global assessment (VAS), BASDAI, tender joints count, swollen joints count except CRP titer show significance difference. Moreover, when they analyzed acute-phase reactant (APR) values for the BASDAI, they found positive correlation between CRP and BASDAI.
Moreover, Korkosz et al. reported significance difference regarding ESR, CRP, and BASDAI score when comparing groups of high disease activity and low disease activity.
On analyzing the correlation of clinical, laboratory, and disease activity parameters in Milanez et al., we found highly significant differences between the patients groups regarding CRP, ESR, BASFI, and ASDAS (CRP).
Moreover, Popescu et al. reported that there was a significant difference regarding disease activity, inflammatory markers, and the functional and activity indices (BASFI, BASDAI) ESR (P = 0.005), CRP (P = 0.012), BASDAI (P < 0.001) and BASFI (P < 0.001) when comparing patients with active and inactive disease; disease activity was measured by BASDAI and BASFI score.
On the contrary, Liu et al. reported no correlation between ESR, CRP, and the disease activity measures and that neither ESR nor CRP is superior for measuring AS disease activity. Moreover, Ozgocmen et al. reported that although acute-phase reactants (ESR and CRP) are important in evaluation of disease and response to treatment, there was a weak relation between APR and AS disease activity.
In the present study, we used BASDAI score and ASDAS (CRP and ESR) as methods for measuring disease activity in AS which were more accurate than other measures.
This comes in agreement with Du et al. who reported BASDAI and ASDAS as good measurements of AS disease activity, and they found that ASDAS is more accurate as clinical indicator of the disease activity of AS, with highest sensitivity reported with ASDAS CRP, and also positive significant correlation when correlating BASDAI and ASDAS with disease activity, which was measured by the patients' global score and the physician global score.
In the same line, Nas et al. and Bobek et al. reported that the ASDAS has the ability to defined the high and low disease activity in subgroups according to BASDAI, which also correlated well with other activity measurements.
| Conclusion|| |
From the present study, we concluded that serum IL-17A levels were significantly higher in patients with AS than in healthy controls and positively correlated with disease activity. These results suggest the role of IL-17A in the pathogenesis of AS. Clinical trials suggested that blocking of this cytokine could partially relieve inflammatory symptoms and also appears to reduce disease activity.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Tam LS, Gu J, Yu D. Pathogenesis of ankylosing spondylitis. Nat Rev Rheumatol 2010; 6
Bal A, Unlu E, Bahar G, Aydog E, Eksioglu E, Yorgancioglu R. Comparison of serum IL-1 beta, sIL-2R, IL-6, and TNF-alpha levels with disease activity parameters in ankylosing spondylitis. Clin Rheumatol 2007; 26
Baeten D, Baraliakos X, Braun J, Sieper J, Emery P, van der Heijde D, et al
. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet 2013; 382
Mei Y, Pan F, Gao J, GeR, Duan Z, Zeng Z, et al
. Increased serum IL-17 and IL-23 in the patient with ankylosing spondylitis. Clin Rheumatol 2011; 30
Chiricozzi A, Guttman-Yassky E, Suárez-Fariñas M, Nograles KE, Tian S, Cardinale I, et al
. Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol 2011; 131
Rouvier E, Luciani MF, Mattéi MG, Denizot F, Golstein P. CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol 1993; 150
Rudwaleit M, Braun J, Sieper J. ASAS classification criteria for axial spondyloarthritis Assessment of Spondylo Arthritis international Society. Z Rheumatol 2009; 68
Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994; 21
Lukas C, Landewé R, Sieper J. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009; 68
Chen WS, Chang YS, Lin KC, Lai CC, Wang SH, Hsiao KH, et al
. Association of serum interleukin-17 and interleukin-23 levels with disease activity in Chinese patients with ankylosing spondylitis. J Chin Med Assoc 2012; 75
Londono J, Romero-Sanchez MC, Torres VG, Bautista WA, Fernandez DJ, Quiroga Jde A, et al
. The association between serum levels of potential biomarkers with the presence of factors related to the clinical activity and poor prognosis in spondyloarthritis. Rev Bras Reumatol 2012; 52
Romero-Sanchez C, Jaimes DA, Londoño J, De Avila J, Castellanos JE, Bello JM, et al
. Association between Th-17 cytokine profile and clinical features in patients with spondyloarthritis. Clin Exp Rheumatol 2011; 29
Baek HJ, Shin KC, Lee YJ, Kang SW, Lee EB, Yoo CD, et al
. Clinical features of adult-onset ankylosing spondylitis in Korean patients: patients with peripheral joint disease (PJD) have less severe spinal disease course than those without PJD. Rheumatology Oxf 2004; 43
Liu XY, XueB, Wang Y, Liu XY, Xue B, Wang Y, et al
. Elevated serum levels of IL-6 and IL-17 may associate with the development of ankylosing spondylitis. Int J Clin Exp Med 2015; 8
Wang X, Lin Z, Wei Q, Jiang Y, Gu J. Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis. Rheumatol Int 2009; 29
Wendling D, Cedoz JP, Racadot E, Dumoulin G. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine 2007; 74
Taylan A, Sari I, Kozaci DL, Yildiz Y, Bilge S, Coker I, et al
. Evaluation of the T helper 17 axis in ankylosing spondylitis. Clin Rheumatol 2012; 31
Wendling D, Toussirot E. Bone and matrix remodeling markersa new tool for assessment of treatment efficacy in ankylosingspondylitis?. J Rheumatol 2007; 34
Muntean L, Lungu A, Gheorghe SR, Valeanu M, Craciun AM, Felea I, et al
. Elevated serum levels of sclerostin are associated with high disease activity and functional impairment in patients with axial spondyloarthritis. Clin Lab 2016; 62
Sveaas SH, Berg IJ, Provan SA, Semb AG, Olsen IC, Ueland T, et al
. Circulating levels of inflammatory cytokines and cytokine receptors in patients with ankylosing spondylitis: a cross-sectional comparative study. Scand J Rheumatol 2015;44
Yildirim K, Erdal A, Karatay S, Melikoğlu MA, Uğur M, Senel K. Relationship between some acute phase reactants and the Bath Ankylosing Spondylitis Disease Activity Index in patients with ankylosing spondylitis. South Med J 2004; 97
Korkosz M, Gąsowski J, Leszczyński P, Pawlak-Buś K, Jeka S, Kucharska E, et al
. High disease activity in ankylosing spondylitis is associated with increased serum sclerostin level and decreased wingless protein-3a signaling but is not linked with greater structural damage. BMC Musculoskelet Disord 2013; 14
Milanez FM, Saad CG, Viana VT, Moraes JC, Périco GV, Sampaio-Barros PD, et al
. IL-23/Th17 axis is not influenced by TNF-blocking agents in ankylosing spondylitis patients. Arthritis Res Ther 2016; 18
Popescu C, Trandafir M, Bădică AM, Morar F, Predeţeanu D. Ankylosing spondylitis functional and activity indices in clinical practice. J Med Life 2014; 7
Liu B, Guo CY, Liu WQ, Wu N, Xing Q. The value of erythrocyte sedimentation rate and C-reactive protein in evaluating disease activity in ankylosing spondylitis. Zhonghua Nei Ke Za Zhi 2005; 44
Ozgocmen S, Godekmerdan A, Ozkurt-Zengin F. Acute-phase response, clinical measures and disease activity in ankylosing spondylitis. Joint Bone Spine 2007; 74
Du XN, Li Y, Zhang SL, Zhu J, Huang F. The value of ankylosing spondylitis disease activity score in evaluating disease activity of ankylosing spondylitis. Zhonghua Nei Ke Za Zhi 2012; 51
Nas K, Yildirim K, Cevik R, Karatay S, Erdal A, Baysal O, et al
. Discrimination ability of ASDAS estimating disease activity status in patients with ankylosing spondylitis. Int J Rheum Dis 2010; 13
Bobek D, Zagar I, Kovač-Durmiš K, Perić P, Ćurković B, Babić-Naglić Ð. Scoring of disease activity using BASDAI and ASDAS method in ankylosing spondylitis. Reumatizam 2012; 59
[Table 1], [Table 2], [Table 3], [Table 4]