Pulmonary involvement in paediatric systemic lupus erythematosus (pSLE) is not an uncommon finding; however, subclinical affection occurs more frequently. Many studies have reported that cytokine dysregulation as interleukin-17 (IL-17) over-expression plays a key role in the pathogenesis of systemic lupus erythematosus (SLE). We aim to assess serum levels of IL-17 A and their association with pulmonary involvement in children with SLE.
Methods
Serum IL-17A levels – determined by solid phase sandwich ELISA – were assessed in forty-two pSLE patients and compared to 45 age-matched healthy controls. All patients were subjected to pulmonary function tests to detect subclinical pulmonary affection. High-resolution CT (HRCT) chest scan was carried out in patients with abnormal pulmonary function tests (PFTs) and those with chronic respiratory symptoms.
Results
Abnormal PFTs were found in 73% of patients; of them, only 25% had abnormal findings in HRCT chest. Serum levels of IL-17 A were significantly elevated in pSLE patients as compared to healthy controls (p < 0.001). The serum levels of IL-17 A had a highly significant positive correlation with SLEDAI (r = 0.811 and p < 0.001) Strong negative correlation was found between serum levels of IL-17A with both FEV1 and FVC (p < 0.05).
Conclusions
Serum IL-17A is elevated in pSLE patients, which correlates with disease activity. IL-17 seems to have a possible role in the pathogenesis of subclinical lung affection. Abnormal PFTS may be found in pSLE patients even with normal radiology.
NathSKKilpatrickJHarleyJB. Genetics of human systemic lupus erythematosus: the emerging picture. Curr Opin Immunol2004; 16: 794–800.
2.
RanuHWildeMMaddenB. Pulmonary function tests. Ulster Med J2011; 80: 84–90.
3.
HappelKI1ZhengMYoungE. Cutting edge: roles of Toll-like receptor 4 and IL- 23 in IL-17 expression in response to Klebsiella pneumoniae infection. J Immunol2003; 170: 4432–4436.
4.
CowanJPandeySFilionLGAngelJBKumarACameronDW. Comparison of interferon-γ-, interleukin (IL)-17- and IL-22-expressing CD4 T cells, IL-22-expressing granulocytes and proinflammatory cytokines during latent and active tuberculosis infection. Clin Exp Immunol2012; 167: 317–329.
5.
WongCKLitLCTamLSLiEKWongPTLamCW. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol2008; 127: 385–393.
6.
WongCKHoCYLiEKLamCW. Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus2000; 9: 589–593.
7.
GenoveseMC1DurezPRichardsHB, et al.Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study. Ann Rheum Dis2013; 72: 863–869.
LillebyVAaløkkenTMJohansenBFørreØ. Pulmonary involvement in patients with childhood-onset systemic lupus erythematosus. Clin Exp Rheumatol2006; 24: 203–208.
10.
AbdullaEAl-ZakwaniIBaddarSAbdwaniR. Extent of subclinical pulmonary involvement in childhood onset systemic lupus erythematosus in the Sultanate of Oman. Oman Med J2012; 27: 36–39.
11.
BullensDMTruyenECoteurL, et al.IL-17 mRNA in sputum of asthmatic patients: Linking T cell driven inflammation and granulocytic influx?Respir Res2006; 7: 135–135.
12.
AgacheICiobanuCAgacheCAnghelM. Increased serum IL-17 is an independent risk factor for severe asthma. Respir Med2010; 104: 1131–1137.
13.
NewcombDCPeeblesRSJr. Th17-mediated inflammation in asthma. Curr Opin Immunol2013; 25: 755–760.
14.
JiXLiJXuL, et al.IL4 and IL-17A provide a Th2/Th17-polarized inflammatory milieu in favor of TGF-β1 to induce bronchial epithelial–mesenchymal transition (EMT). Int J Clin Exp Pathol2013; 6: 1481–1492.
15.
NembriniC1MarslandBJKopfM. IL-17-producing T cells in lung immunity and inflammation. J Allergy Clin Immunol2009; 123: 986–994.
16.
HochbergMC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1997; 40: 1725–1725.
17.
BombardierCGladmanDDUrowitzMBCaronDChangCH. Derivation of the SLEDAI. A disease activity index for lupus patients. Arthritis Rheum1992; 35: 630–640.
18.
American Thoracic Society. Standardization of Spirometry, 1994 Update. Am J Respir Crit Care Med1995; 152: 1107–1136.
19.
JinDZhangLZhengJZhaoY. The inflammatory Th 17 subset in immunity against self and non-self antigens. Autoimmunity2008; 41: 154–162.
20.
MarwahaAKLeungNJMcMurchyAN. TH17 Cells in Autoimmunity and Immunodeficiency: Protective or Pathogenic?Front Immunol2012; 3: 129–129.
21.
RanaAMinzRWAggarwalRAnandSPasrichaNSinghS. Gene expression of cytokines (TNF-α, IFN-γ), serum profiles of IL-17 and IL-23 in paediatric systemic lupus erythematosus. Lupus2012; 21: 1105–1112.
22.
LiDGuoBWuHTanLChangCLuQ. Interleukin-17 in systemic lupus erythematosus: a comprehensive review. Autoimmunity2015; 48: 353–361.
23.
VincentFBNorthcottMHoiAMackayFMorandEF. Clinical associations of serum interleukin-17 in systemic lupus erythematosus. Arthritis Res Ther2013; 15: R97–R97.
24.
WenZXuLXuWYinZGaoXXiongS. Interleukin-17 expression positively correlates with disease severity of lupus nephritis by increasing anti-double-stranded DNA antibody production in a lupus model induced by activated lymphocyte derived DNA. PLoS One2013; 8: e58161–e58161.
25.
HoffmanIELauwerysBRDe KeyserF, et al.Juvenile-onset systemic lupus erythematosus: different clinical and serological pattern than adult-onset systemic lupus erythematosus. Ann Rheum Dis2009; 68: 412–415.
26.
HammadAMosaadYMHammadEM, et al.Interleukin-17A rs2275913, Interleukin-17F rs763780 and rs2397084 gene polymorphisms as possible risk factors in Juvenile lupus and lupus related nephritis. Autoimmunity2015; 30: 1–10.
27.
Abd El-KhalikKAEl-SayedZAFaheemMSFoudaEAbdurrahmanLAbd El-GhanyS. High resolution computed tomography and pulmonary function tests in childhood systemic lupus erythematosus and juvenile rheumatoid arthritis. Egypt J Pediatr Allergy Immunol2004; 2: 8–15.
28.
CrispínJCOukkaMBaylissG, et al.Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J Immunol2008; 181: 8761–8766.
29.
ZhangZKyttarisVCTsokosGC. The role of IL-23/IL-17 axis in lupus nephritis. J Immunol2009; 183: 3160–3169.
30.
AlamMMSarkarSGhoshP, et al.Spirometric evaluation in juvenile systemic lupus erythematosus. Indian Pediatr2014; 51: 909–911.
31.
LotfyHHalawaEEl BazM. Pulmonary involvement in juvenile-onset systemic lupus erythematosus patients asymptomatic for respiratory disease. Egypt J Bronchol2015; 9: 59–59.
32.
FenlonHMDoranMSantSMBreatnachE. High-resolution chest CT in systemic lupus erythematosus. Am J Roentgenol1996; 166: 301–307.
33.
SantSMDoranMFenelonHMBreatnachES. Pleuropulmonary abnormalities in patients with systemic lupus erythematosus: assessment with high resolution computed tomography, chest radiography and pulmonary function tests. Clin Exp Rheumatol1997; 15: 507–513.
34.
TrapaniSCamiciottoliGErminiMCastellaniWFalciniF. Pulmonary involvement in juvenile systemic lupus erythematosus: a study on lung function in patients asymptomatic for respiratory disease. Lupus1998; 7: 545–550.
35.
ChangYAl-AlwanLRissePA, et al.Th17-associated cytokines promote human airway smooth muscle cell proliferation. FASEB J2012; 26: 5152–5160.
36.
AlcornJFCroweCRKollsJK. Th17 cells in asthma and COPD. Annu Rev Physiol2010; 72: 495–516.
