Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2010

Open Access 01-02-2010 | Research article

Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment

Authors: Lisa GM van Baarsen, Carla A Wijbrandts, François Rustenburg, Tineke Cantaert, Tineke CTM van der Pouw Kraan, Dominique L Baeten, Ben AC Dijkmans, Paul P Tak, Cornelis L Verweij

Published in: Arthritis Research & Therapy | Issue 1/2010

Login to get access

Abstract

Introduction

Cross-regulation between TNF and type I IFN has been postulated to play an important role in autoimmune diseases. Therefore, we determined the effect of TNF blockade in rheumatoid arthritis (RA) on the type I IFN response gene activity in relation to clinical response.

Methods

Peripheral blood from 33 RA patients was collected in PAXgene tubes before and after the start of infliximab treatment. In a first group of 15 patients the baseline expression of type I IFN-regulated genes was determined using cDNA microarrays and compared to levels one month after treatment. The remaining 18 patients were studied as an independent group for validation using quantitative polymerase chain reaction (qPCR).

Results

Gene expression analysis revealed that anti-TNF antibody treatment induced a significant increase in type I IFN response gene activity in a subset of RA patients, whereas expression levels remained similar or were slightly decreased in others. The findings appear clinically relevant since patients with an increased IFN response gene activity after anti-TNF therapy had a poor clinical outcome. This association was confirmed and extended for an IFN response gene set consisting of OAS1, LGALS3BP, Mx2, OAS2 and SERPING1 in five EULAR good and five EULAR poor responders, by qPCR.

Conclusions

Regulation of IFN response gene activity upon TNF blockade in RA is not as consistent as previously described, but varies between patients. The differential changes in IFN response gene activity appear relevant to the clinical outcome of TNF blockade in RA.
Appendix
Available only for authorised users
Literature
1.
Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, Shark KB, Grande WJ, Hughes KM, Kapur V, Gregersen PK, Behrens TW: Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci USA. 2003, 100: 2610-2615.PubMedCentralCrossRefPubMed
2.
Baechler EC, Gregersen PK, Behrens TW: The emerging role of interferon in human systemic lupus erythematosus. Curr Opin Immunol. 2004, 16: 801-807.CrossRefPubMed
3.
Ronnblom LE, Alm GV, Oberg KE: Autoimmunity after alpha-interferon therapy for malignant carcinoid tumors. Ann Intern Med. 1991, 115: 178-183.CrossRefPubMed
4.
Feldmann M, Maini RN: Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?. Annu Rev Immunol. 2001, 19: 163-196.CrossRefPubMed
5.
Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, Leeb B, Breedveld FC, Macfarlane JD, Bijl H: Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet. 1994, 344: 1105-1110.CrossRefPubMed
6.
Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T, DeWoody KL, Schaible TF, Rutgeerts PJ: A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med. 1997, 337: 1029-1035.CrossRefPubMed
7.
Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP: Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008, 117: 244-279.CrossRefPubMed
8.
Banchereau J, Pascual V, Palucka AK: Autoimmunity through cytokine-induced dendritic cell activation. Immunity. 2004, 20: 539-550.CrossRefPubMed
9.
Palucka AK, Blanck JP, Bennett L, Pascual V, Banchereau J: Cross-regulation of TNF and IFN-alpha in autoimmune diseases. Proc Natl Acad Sci USA. 2005, 102: 3372-3377.PubMedCentralCrossRefPubMed
10.
Kimura Y, Pinho P, Walco G, Higgins G, Hummell D, Szer I, Henrickson M, Watcher S, Reiff A: Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol. 2005, 32: 935-942.PubMed
11.
Mavragani CP, Niewold TB, Moutsopoulos NM, Pillemer SR, Wahl SM, Crow MK: Augmented interferon-alpha pathway activation in patients with Sjogren's syndrome treated with etanercept. Arthritis Rheum. 2007, 56: 3995-4004.PubMedCentralCrossRefPubMed
12.
Mariette X, Ravaud P, Steinfeld S, Baron G, Goetz J, Hachulla E, Combe B, Puechal X, Pennec Y, Sauvezie B, Perdriger A, Hayem G, Janin A, Sibilia J: Inefficacy of infliximab in primary Sjogren's syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjogren's Syndrome (TRIPSS). Arthritis Rheum. 2004, 50: 1270-1276.CrossRefPubMed
13.
Pouw Kraan van der TC, Wijbrandts CA, van Baarsen LG, Voskuyl AE, Rustenburg F, Baggen JM, Ibrahim SM, Fero M, Dijkmans BA, Tak PP, Verweij CL: Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients. Ann Rheum Dis. 2007, 66: 1008-1014.PubMedCentralCrossRefPubMed
14.
Bokarewa M, Tarkowski A, Lind M, Dahlberg L, Magnusson M: Arthritogenic dsRNA is present in synovial fluid from rheumatoid arthritis patients with an erosive disease course. Eur J Immunol. 2008, 38: 3237-3244.CrossRefPubMed
15.
van Gestel AM, Prevoo ML, van 't Hof MA, van Rijswijk MH, Putte van de LB, van Riel PL: Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum. 1996, 39: 34-40.CrossRefPubMed
16.
Fransen J, van Riel PL: The Disease Activity Score and the EULAR response criteria. Clin Exp Rheumatol. 2005, 23: S93-S99.PubMed
17.
van Gestel AM, Haagsma CJ, van Riel PL: Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998, 41: 1845-1850.CrossRefPubMed
18.
19.
Pouw Kraan van der TC, van Baarsen LG, Rustenburg F, Baltus B, Fero M, Verweij CL: Gene expression profiling in rheumatology. Methods Mol Med. 2007, 136: 305-327.CrossRefPubMed
20.
Demeter J, Beauheim C, Gollub J, Hernandez-Boussard T, Jin H, Maier D, Matese JC, Nitzberg M, Wymore F, Zachariah ZK, Brown PO, Sherlock G, Ball CA: The Stanford Microarray Database: implementation of new analysis tools and open source release of software. Nucleic Acids Res. 2007, 35: D766-D770.PubMedCentralCrossRefPubMed
21.
22.
van Baarsen LG, Pouw Kraan van der TC, Kragt JJ, Baggen JM, Rustenburg F, Hooper T, Meilof JF, Fero MJ, Dijkstra CD, Polman CH, Verweij CL: A subtype of multiple sclerosis defined by an activated immune defense program. Genes Immun. 2006, 7: 522-531.CrossRefPubMed
23.
24.
Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, Pascual V: Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med. 2003, 197: 711-723.PubMedCentralCrossRefPubMed
25.
Han GM, Chen SL, Shen N, Ye S, Bao CD, Gu YY: Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray. Genes Immun. 2003, 4: 177-186.CrossRefPubMed
26.
Kirou KA, Lee C, George S, Louca K, Peterson MG, Crow MK: Activation of the interferon-alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum. 2005, 52: 1491-1503.CrossRefPubMed
27.
Baechler EC, Bauer JW, Slattery CA, Ortmann WA, Espe KJ, Novitzke J, Ytterberg SR, Gregersen PK, Behrens TW, Reed AM: An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity. Mol Med. 2007, 13: 59-68.PubMedCentralCrossRefPubMed
28.
Charles PJ, Smeenk RJ, De Jong J, Feldmann M, Maini RN: Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha: findings in open-label and randomized placebo-controlled trials. Arthritis Rheum. 2000, 43: 2383-2390.CrossRefPubMed
29.
Maini RN, Elliott MJ, Charles PJ, Feldmann M: Immunological intervention reveals reciprocal roles for tumor necrosis factor-alpha and interleukin-10 in rheumatoid arthritis and systemic lupus erythematosus. Springer Semin Immunopathol. 1994, 16: 327-336.CrossRefPubMed
30.
Cantaert T, van Baarsen EGM, Wijbrandts CA, Thurlings RM, Sande van de MG, Bos C, Pouw Kraan van der TCTM, Verweij CL, Tak PP, Baeten D: Type I interferons have no major influence on humoral autoimmunity in rheumatoid arthritis. Rheumatology. 2009
31.
Cantaert T, De Rycke L, Mavragani CP, Wijbrandts CA, Niewold TB, Niers T, Vandooren B, Veys EM, Richel D, Tak PP, Crow MK, Baeten D: Exposure to nuclear antigens contributes to the induction of humoral autoimmunity during TNF alpha blockade. Ann Rheum Dis. 2008, 68: 1022-1029.PubMedCentralCrossRefPubMed
32.
Yarilina A, Park-Min KH, Antoniv T, Hu X, Ivashkiv LB: TNF activates an IRF1-dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon-response genes. Nat Immunol. 2008, 9: 378-387.CrossRefPubMed
33.
Sigurdsson S, Nordmark G, Goring HH, Lindroos K, Wiman AC, Sturfelt G, Jonsen A, Rantapaa-Dahlqvist S, Moller B, Kere J, Koskenmies S, Widen E, Eloranta ML, Julkunen H, Kristjansdottir H, Steinsson K, Alm G, Ronnblom L, Syvanen AC: Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am J Hum Genet. 2005, 76: 528-537.PubMedCentralCrossRefPubMed
34.
Sigurdsson S, Nordmark G, Garnier S, Grundberg E, Kwan T, Nilsson O, Eloranta ML, Gunnarsson I, Svenungsson E, Sturfelt G, Bengtsson AA, Jonsen A, Truedsson L, Rantapaa-Dahlqvist S, Eriksson C, Alm G, Goring HH, Pastinen T, Syvanen AC, Ronnblom L: A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5. Hum Mol Genet. 2008, 17: 2868-2876.PubMedCentralCrossRefPubMed
35.
Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW, de Bakker PI, Le JM, Lee HS, Batliwalla F, Li W, Masters SL, Booty MG, Carulli JP, Padyukov L, Alfredsson L, Klareskog L, Chen WV, Amos CI, Criswell LA, Seldin MF, Kastner DL, Gregersen PK: STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med. 2007, 357: 977-986.PubMedCentralCrossRefPubMed
36.
Dieguez-Gonzalez R, Calaza M, Perez-Pampin E, de la Serna AR, Fernandez-Gutierrez B, Castaneda S, Largo R, Joven B, Narvaez J, Navarro F, Marenco JL, Vicario JL, Blanco FJ, Fernandez-Lopez JC, Caliz R, Collado-Escobar MD, Carreno L, Lopez-Longo J, Canete JD, Gomez-Reino JJ, Gonzalez A: Association of interferon regulatory factor 5 haplotypes, similar to that found in systemic lupus erythematosus, in a large subgroup of patients with rheumatoid arthritis. Arthritis Rheum. 2008, 58: 1264-1274.CrossRefPubMed
37.
Sigurdsson S, Padyukov L, Kurreeman FA, Liljedahl U, Wiman AC, Alfredsson L, Toes R, Ronnelid J, Klareskog L, Huizinga TW, Alm G, Syvanen AC, Ronnblom L: Association of a haplotype in the promoter region of the interferon regulatory factor 5 gene with rheumatoid arthritis. Arthritis Rheum. 2007, 56: 2202-2210.CrossRefPubMed
Metadata
Title
Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment
Authors
Lisa GM van Baarsen
Carla A Wijbrandts
François Rustenburg
Tineke Cantaert
Tineke CTM van der Pouw Kraan
Dominique L Baeten
Ben AC Dijkmans
Paul P Tak
Cornelis L Verweij
Publication date
01-02-2010
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2010
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2912

Other articles of this Issue 1/2010

Arthritis Research & Therapy 1/2010 Go to the issue

Research article

Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease

Research article

CD16 (FcRγIII) as a potential marker of osteoclast precursors in psoriatic arthritis

Research article

Forefoot disease activity in rheumatoid arthritis patients in remission: results of a cohort study

Research article

Development of bone marrow lesions is associated with adverse effects on knee cartilage while resolution is associated with improvement - a potential target for prevention of knee osteoarthritis: a longitudinal study

Research article

S100A8 and S100A9 in experimental osteoarthritis

Editorial

When rheumatology meets hepatology: are anti-TNFs safe in hepatitis B virus carriers?
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits