ORIGINAL PAPER
Inflammatory bowel disease-related arthritis – clinical evaluation and possible role of cytokines
More details
Hide details
Submission date: 2015-10-08
Final revision date: 2015-10-23
Acceptance date: 2015-10-24
Online publication date: 2015-12-08
Publication date: 2015-12-31
Reumatologia 2015;53(5):236-242
KEYWORDS
TOPICS
ABSTRACT
Objectives: In inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation, rheumatic abnormalities ranging from arthralgia to spondyloarthritis (SpA) are the most common extraintestinal manifestations. The pathogenesis of IBD-related arthritis is unclear. In this study, we search for clinical and immunological differences between patients with IBD-associated spondyloarthritis and IBD patients without SpA symptoms.
Material and methods: Patients with an established diagnosis of IBD, suffering from Leśniowski-Crohn disease (L-CD, n = 24) or ulcerative colitis (UC, n = 27), were enrolled in the study. Clinical evaluation of patients, based on medical history, blood tests, physical and radiological examinations, allowed two subgroups of patients to be established. One subgroup comprised patients fulfilling criteria for both IBD and SpA (IBD + SpA, n = 29), while the other included IBD patients with arthralgia only (IBD, n = 22). Serum concentrations of interleukins (IL-6, IL-10, IL-21, IL-22, IL-23) and interferon (IFN-) were measured by specific enzyme-linked immunosorbent assays (ELISA).
Results: Patients with IBD + SpA were characterized by shorter disease duration (3 vs. 9 years), higher frequency of HLA-B27 positivity (60.7% vs. 4.5%) and uveitis (20.7% vs. 0%), compared with the IBD subgroup. The serum concentrations of C-reactive protein (CRP) and tested cytokines did not differ between IBD + SpA and IBD patients, or between L-CD and UC groups. However, in the IBD + SpA subgroup there was weak to moderate positive correlation between serum concentrations of CRP and several cytokines (IL-6, IL-21, IFN-), and additional moderate positive correlation between serum concentrations of IL-23 and clinical activity of SpA. By contrast, in IBD subgroup a strong inverse correlation between serum concentrations of Interleukin 23 and CRP was found.
Conclusions: IBD-related spondyloarthritis occurs relatively early, affects mostly HLA-B27(+) individuals, and is often accompanied by ocular involvement. In these patients several circulating cytokines are associated with systemic inflammation. IL-23 seems to be protective in IBD while detrimental in IBD-related spondyloarthritis.
REFERENCES (31)
1.
Salvarani C, Fries W. Clinical features and epidemiology of spondyloarthritides associated with inflammatory bowel disease. World J Gastroenterol 2009; 15: 2449-2455.
2.
Salvarani C, Vlachonikolis IG, van der Heijde DM, et al. Musculoskeletal manifestations in population-based cohort of inflammatory bowel disease patients. Scand J Gastroenterol 2001; 36: 1307-1313.
3.
Rodríguez-Reyna TS, Martínez-Reyes C, Yamamoto-Furusho JK.
4.
Rheumatic manifestations of inflammatory bowel disease. World J Gastroenterol 2009; 15: 5517-5524.
5.
Leirisalo-Repo M, Turunen U, Stenman S, et al. High frequency of silent inflammatory bowel disease in spondylarthropathy. Arthritis Rheum 1994; 37: 23-31.
6.
Shih DQ, Targan SR, McGovern D. Recent advances in IBD pathogenesis: genetics and immunobiology. Curr Gastroenterol Rep 2008; 10: 568-575.
7.
De Keyser F, Baeten D, Van den Bosch F, et al. Gut inflammation and spondyloarthropathies. Curr Rheumatol Rep 2002; 4: 525-532.
8.
Mielants H, De Keyser F, Baeten D, et al. Gut inflammation in the spondyloarthropathies. Curr Rheumatol Rep 2005; 7: 188-194.
9.
Alonso Farto JC, Arias IA, Lopez Longo FJ, et al. Clinical significance of abdominal scintigraphy using 99mTc-HMPAO-labelled leucocytes in patients with seronegative spondyloarthropathies. Eur J Nucl Med 2000; 27: 1768-1773.
10.
Breese E, Braegger CP, Corrigan CJ, et al. Interleukin-2 and interferon-gamma secreting T cells in normal and diseased human intestinal mucosa. Immunology 1993; 78: 127-131.
11.
Noguchi M, Hiwatashi N, Liu Z, et al. Enhanced interferon-gamma production and B7-2 expression in isolated intestinal mononuclear cells from patients with Crohn’s disease. J Gastroenterol 1995; 30 (Suppl 8): 52-55.
12.
Fujino S, Andoh A, Bamba S, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 2003; 52: 65-70.
13.
Ahern PP, Izcue A, Maloy KJ, et al. The interleukin-23 axis in intestinal inflammation. Immunol Rev 2008; 226: 147-159.
14.
Abraham C, Cho J. Interleukin-23/Th17 pathways and inflammatory bowel disease. Inflamm Bowel Dis 2009; 15: 1090-1100.
15.
Monteleone I, Pallone F, Monteleone G. Interleukin-23 and Th17 cells in the control of gut inflammation. Meditors Inflamm 2009; 2009: article ID 297645.
16.
Hamilton MJ, Snapper SB, Blumberg RS. Update on biologic pathways in inflammatory bowel disease and their therapeutic relevance. J Gastroenterol 2012; 47: 1-8.
17.
Singh AK, Misra R, Aggrawal A. Th-17 associated cytokines in patients with reactive arthritis/undifferentiated spondyloarthropathy. Clin Rheumatol 2011; 30: 771-776.
18.
Rasmussen TK, Andersen T, Hvid M, et al. Increased interleukin 21 (IL-21) and IL-23 are associated with increased disease activity and with radiographic status in patients with early rheumatoid arthritis. J Rheumatol 2010; 37: 2014-2020.
19.
Braat H, Peppelenbosch MP, Hommes DW. Interleukin-10-based therapy for inflammatory bowel disease. Expert Opin Biol Ther 2003; 3: 725-731.
20.
Kontny E, Maśliński W. Sieć cytokin i implikacje terapeutyczne w chorobach reumatycznych. In: Leczenie biologiczne chorób reumatycznych. Wiland P (ed.). Termedia Wydawnictwo Medyczne, Poznań 2009.
21.
Rudwaleit M, van der Heijde D, Landewé R, et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011; 70: 25-31.
22.
Korolkova OY, Myers JN, Pellom ST, et al. Characterization of serum cytokine profile in predominantly colonic inflammatory bowel disease to delineate ulcerative and Crohn’s colitides. Clin Med Insights Gastroenterol 2015; 8: 29-44.
23.
Kontny E. Nowe aspekty patogenezy spondyloartropatii zapalnych. Część I – uwarunkowania genetyczne, rola cząsteczek HLA-B27. Reumatologia 2014; 52: 105-111.
24.
Neurath MF. New targets for mucosal healing and therapy in inflammatory bowel diseases. Mucosal Immunol 2014; 7: 6-19.
25.
Przepiera-Będzak H, Fischer K, Brzosko M. Serum IL-6 and IL-23 levels and their correlation with angiogenic cytokines and disease activity in ankylosing spondylitis. Mediators Inflamm 2015; 2015: article ID 785705.
26.
De Nitto D, Sarra M, Pallone F, et al. Interleukin-21 triggers effector cell response in the gut. World J Gastroenterol 2010; 7: 3638-3641.
27.
Madej M, Nowak B, Świerkot J, et al. Cytokine profiles in axial spondyloarthritis. Reumatologia 2015; 53: 9-13.
28.
Chen WS, Chang YS, Lin KC, 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: 303-308.
29.
Becker C, Dornhoff H, Neufert C, et al. Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. J Immunol 2006; 177: 2760-2764.
30.
Sandborn WJ, Gasink C, Gao LL. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med 2012; 367: 1519-1528.
31.
van den Bosch F, Deodhar A. Treatment of spondyloarthritis beyond TNF-αlpha blockade. Best Pract Res Clin Rheumatol 2014; 28: 819-827.
Copyright: © Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie. This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (
https://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.