The Role of Alpha Defensins in Patients with Ankylosing Spondylitis

Abstract

Objectives Defensins are a family of antimicrobial peptides. Elevated levels of human neutrophil peptides (HNP 1–3) are seen in blood samples of patients with inflammatory bowel disease (IBD) and in many rheumatic diseases. It has been suggested that they may play a significant role in the progression and pathogenesis of these diseases. Therefore, we aimed to investigate the levels of HNP 1–3 in sera of patients with ankylosing spondylitis (AS) and its association with disease activity and other clinical features of AS.

Methods A total of 36 patients, who met the Modified New York Criteria for AS, and 50 healthy controls (HCs) were included in this study. The Bath AS Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) were used to assess disease activity. The Bath AS Radiology Index (BASRI) was used to assess radiological damage. Spinal and hip measurements were determined by the Bath AS Metrology Index (BASMI). An AS Quality of Life (ASQoL) questionnaire was administered to assess the disease-related quality of life. Serum HNP 1–3 levels were determined using the ELISA kit.

Results Mean serum HNP 1–3 levels were significantly higher in patients with AS (287.01±201.307 vs. 152.09±43.75 pg/ml) compared with HCs (p=0.001). HNP 1–3 levels did not correlate with BASDAI (p=0.519), ASDAS-CRP (p=0.424), BASRI (p=0.280), BASMI (p=0.168), ASQoL (p=0.307), ESR (p=0.706) and CRP (p=0.157) values.

Conclusion Elevated serum levels of HNP 1–3 may play an important role in the pathogenetic mechanisms of AS. This result may give us an opportunity to develop new treatment strategies considering the role of these peptides in the pathogenetic mechanisms of AS.

Zusammenfassung

Zielsetzung Defensine sind eine Familie antimikrobieller Peptide. Erhöhte Spiegel an humanen neutrophilen Peptiden (HNP 1–3) wurden in Blutproben von Patienten mit entzündlicher Darmerkrankung (IBD) und bei vielen rheumatischen Erkrankungen gezeigt. Es wurde vermutet, dass sie eine bedeutende Rolle bei der Progression und Pathogenese dieser Krankheiten spielen könnten. Daher wollten wir die HNP 1–3-Spiegel in Seren von Patienten mit ankylosierender Spondylitis (AS) und deren Zusammenhang mit der Krankheitsaktivität und anderen klinischen Merkmalen untersuchen.

Methoden Insgesamt 36 Patienten, die die modifizierten New Yorker Kriterien für AS und 50 gesunde Kontrollen (HCs) erfüllten, wurden in diese Studie eingeschlossen. Der Bath AS Disease Activity Index (BASDAI) und der Ankylosing Spondylitis Disease Activity Score (ASDAS) wurden verwendet, um die Krankheitsaktivität zu bewerten. Der Bath AS Radiology Index (BASRI) wurde verwendet, um radiologische Schäden zu bewerten. Wirbelsäulen- und Hüftmessungen wurden mit dem Bath AS Metrology Index (BASMI) bestimmt. Zur Beurteilung der krankheitsbedingten Lebensqualität wurde ein ASQoL-Fragebogen (AS Quality of Life) ausgefüllt. Die Serum-HNP-1–3-Spiegel wurden unter Verwendung eines ELISA-Kits bestimmt.

Ergebnisse Der mittlere HNP 1–3-Spiegel im Serum war bei Patienten mit AS signifikant höher (287,01±201,307 gegenüber 152,09±43,75 pg / ml) als bei HCs (p=0,001). Die HNP 1–3-Spiegel korrelierten nicht mit BASDAI (p=0,519), ASDAS-CRP (p=0,424), BASRI (p=0,280), BASMI (p=0,168), ASQoL (p=0,307), ESR (p =) 0,706) und CRP (p=0,157).

Schlussfolgerung Erhöhte Serumspiegel von HNP 1–3 können eine wichtige Rolle für die pathogenetischen Mechanismen der AS spielen. Dieses Ergebnis könnte uns eine neue Gelegenheit geben, neue Therapiestrategien unter Berücksichtigung der Rolle dieser Peptide in den pathogenetischen Mechanismen der AS zu entwickeln.

Key words

humane neutrophile Peptide 1–3 - Spondylitis ankylosans - Krankheitsaktivität

Schlüsselwörter

human neutrophil peptides 1–3 - ankylosing spondylitis - disease activity

Publication History

Article published online:
06 October 2020

• References

• 1 Mielants H, Veys EM, Cuvelier C. et al. HLA-B27 related arthritis and bowel inflammation. Part 2. Ileocolonoscopy and bowel histology in patients with HLA-B27 related arthritis. J Rheumatol 1985; 12: 294-298
• 2 Mielants H, Bosch F. Inflammatory bowel disease spondyloarthritis: epidemiology, clinical features, and treatment. In Ankylosing Spondylitis and the Spondlyoarthropathies. 1 edition Edited by Weisman MH, Reveille JD, van der Heijde D Philadelphia, PA: Mosby; 2006
• 3 Matzkies FG, Targan SR, Berel D. et al. Markers of intestinal inflammation in patients with ankylosing spondylitis: a pilot study. Arthritis Res Ther 2012; 14: R261
• 4 Turkcapar N, Toruner M, Soykan I. et al. The prevalence of extraintestinal manifestations and HLA association in patients with inflammatory bowel disease. Rheumatol Int 2006; 26: 663-668
• 5 Elewaut D. Linking Crohn’s disease and ankylosing spondylitis: it’s all about genes. PLoS Genet 2010; 6: e1001223
• 6 Yang D, Biragyn A, Hoover DM. et al. Multiple roles of antimicrobial defensins, cathelicidins, and eosionphil- derived neurotoxin in host defence. Annu Rev Immunol 2004; 22: 181-215
• 7 Wehkamp J, Stange EF, Fellermann K. Defensin-immunology in inflammatory bowel disease. Gastroenterol Clin Biol 2009; 33: 137-144
• 8 Ramasundara M, Leach ST, Lemberg DA. et al. Defensins and inflammation: the role of defensins in inflammatory bowel disease. J Gastroenterol Hepatol 2009; 24: 202-208
• 9 Cunliffe RN. Alpha-defensins in the gastrointestinal tract. Mol Immunol 2003; 40: 463-467
• 10 Ciccia F, Bombardieri M, Rizzo A. et al. Over-expression of paneth cell-derived anti-microbial peptides in the gut of patients with ankylosing spondylitis and subclinical intestinal inflammation. Rheumatology (Oxford) 2010; 49: 2076-2083
• 11 Garrett S, Jenkinson T, Kennedy LG. et al. A new approach to defining disease status in ankylosing spondylitis: the bath ankylosing spondylitis disease activity index. J Rheumatol 1994; 21: 2286-2291
• 12 Lukas C, Landewe R, Sieper J. et al. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009; 68: 18Y24
• 13 Mackay K, Mack C, Brophy S. et al. The Bath Ankylosing Spondylitis Radiology Index (BASRI). A new validated approach to diseases assessment. Arthritis Rheum 1998; 41: 2263
• 14 Jenkinson TR, Mallorie PA, Whitelock HC. et al. Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. J Rheumatol 1994; 21: 1694-1698
• 15 Doward LC, Spoorenberg A, Cook SA. et al. Development of ASQoL: a quality of life instrument specific to ankylosing spondylitis. Ann Rheum Dis 2003; 62: 20-26
• 16 Pöllänen R, Sillat T, Pajarinen J. et al. Microbial antigens mediate HLA-B27 diseases via TLRs. J Autoimmun 2009; 32: 172-177
• 17 Menendez A, Brett FB. Defensins in the immunology of bacterial infections. Curr Opin Immunol 2007; 19: 385-391
• 18 Soehnlein O. Kai-Larsen et al. Neutrophil primary granule proteins HBP and HNP1-3 boost bacterial phagocytosis by human and murine macrophages. J Clin Invest 2008; 118: 3491-3502
• 19 Stebbings SM, Taylor C, Tannock GW. et al. The immune response to autologous bacteroides in ankylosing spondylitis is chacacterized by reduced interleukin 10 production. J Rheumatol 2009; 36: 797-800
• 20 Simms LA, Doecke JD, Walsh MD. et al. Reduced alpha-defensin expression is associated with inflammation and not NOD2 mutation status in ileal Crohn’s disease. Gut 2008; 57: 903-910
• 21 Yamaguchi N, Isomoto H, Mukae H. et al. Concentrations of alpha- and beta-defensins in plasma of patients with inflammatory bowel disease. Inflamm Res 2009; 58: 192-197
• 22 Van Praet L, Van den Bosch FE, Jacques P. et al. Microscopic gut inflammation in axial spondyloarthritis: a multiparametric predictive model. Ann Rheum Dis 2013; 72: 414-417
• 23 Kanmura S, Uto H, Numata M. et al Human neutrophil peptides 1–3 are useful biomarkers in patients with active ulcerative colitis. Inflamm Bowel Dis 2009; 15: 909-917
• 24 Bokarewa MI, Jin T, Tarkowski A. Intraarticular release and accumulation of defensins and bactericidal/permeability-increasing protein in patients with rheumatoid arthritis. J Rheumatol 2003; 30: 1719-1724
• 25 Vordenbäumen S, Fischer-Betz R, Timm D. et al. Elevated levels of human beta-defensin 2 and human neutrophil peptides in systemic lupus erythematosus. Lupus 2010; 19: 1648-1653
• 26 Cunliffe RN, Kamal M, Rose F. et al. Expression of antimicrobial neutrophil defensins in epithelial cells of active inflammatory bowel disease mucosa. J Clin Pathol 2002; 55: 298-304
• 27 Bokarewa MI, Jin T, Tarkowski A. Intraarticular release and accumulation of defensins and bactericidal/permeability-increasing protein in patients with rheumatoid arthritis. J Rheumatol 2003; 30: 1719-1724
• 28 Okçu M, Oktayoglu P, Mete N. et al. A useful marker in assessment of remission and activation of disease in patients with rheumatoid arthritis: Serum human neutrophil peptides 1-3. J Back Muscoloskelet Rehabil 2018; 31: 1145-1150
• 29 Bodur H, Ataman S, Bugdaycı DS. et al. Turkiye Romatizma Araştırma ve Savaş Derneği [TRASD] (Turkish League Against Rheumatism) Ankylosing Spondylitis [AS] Study Group. Description of the registry of patients with ankylosing spondylitis in Turkey: TRASD-IP. Rheumatol Int 2012; 32: 169-176