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C-Reactive Protein in Inflammatory Bowel Disease

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Clinical Significance of C-reactive Protein

Abstract

Crohn’s disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD) which are characterized by chronic idiopathic inflammatory damage to the intestine. Though they share some common inflammatory pathways, still they can be distinguished clinically, endoscopically, and histologically. Even after intense research, the etiology for IBD remains unknown. Defective immune regulation, altered gut microbiota, and other environmental factors trigger immune cascade in the background of genetic predisposition in patients with IBD. Activation of helper T cells, i.e., TH1 and TH17, and sequential cascade of inflammatory mediators involving IL-1, IL-4, IL-5, IL-6, and TNF and other cytokines play the major role in IBD. Each step of this inflammatory cascade is not only potential target for therapy, the markers of inflammation may guide us for diagnosing, confirming the diagnosis even in follow-up, and prognostication in IBD. Serum biomarkers are mainly markers of inflammation, i.e., C-reactive protein (CRP), ESR, ferritin, or antibodies, i.e., ANCA (anti-neutrophilic cytoplasmic antibody), ASCA anti-OmpC whereas stool markers are mainly leukocyte-derived molecules like fecal calprotectin and lactoferrin. CRP is an acute phase reactant protein secreted by the hepatocyte cells in response to stimulation by circulating IL-6 and TNF-α. CRP level ranges from 5 to 200 mg/L. CRP level sharply rises following any inflammatory condition due to increased recruitment of hepatocytes and decrease of its peak also follows a sharp trend. CRP has been incorporated in the assessment of severity of UC (Truelove and Witts criteria) though various studies have shown that clear increase of CRP is much more prominent in CD than UC, the reason of which is not still very clear and satisfactory. Two explanations for that are higher IL-6 concentration and transmural involvement of intestine in CD. Though not specific, still CRP remains one of the very important biomarkers in IBD.

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Abbreviations

AGR2:

Anterior gradient 2

ANCA:

Anti-neutrophilic cytoplasmic antibody

ASA:

5-Aminosalicylic acid

ASCA:

Anti-saccharomyces cerevisiae antibody

ATG16L1:

Autophagy-related 16 like 1

CCR6:

C-C chemokine receptor 6

CCR9:

C-C chemokine receptor type 9

CD:

Crohn’s disease

CRC:

Colorectal cancer

CRP:

C-reactive protein

CT:

Computed tomography

CTE:

Computed tomography enterography

DC:

Dendritic cell

EIMs:

Extra-intestinal manifestations

ER:

Endoplasmic reticulum

ESR:

Erythrocyte sedimentation rate

FOXP3:

Forkhead box P3

GC:

Glucocorticosteroid

GI:

Gastrointestinal

IBD:

Inflammatory bowel disease

IBS:

Irritable bowel syndrome

IFN:

Interferon

IgA:

Immunoglobulin A

IgG:

Immunoglobulin G

IL:

Interleukins

IL23R:

Interleukin 23 receptor

IPAA:

Ileal pouch/anal anastomosis

IRGM:

Immunity-related GTPase family M protein

IV:

Intravenous

JAK2:

Janus kinase 2

JAK-STAT:

Janus-associated kinase signal transducers and activators of transcription proteins

MAP:

Mitogen-activated protein

mCRP:

Monomeric CRP

MMP:

Matrix metalloproteinase

MRE:

Magnetic resonance enterography

MRI:

Magnetic resonance imaging

MST1:

Macrophage-stimulating 1 gene

MTX:

Methotrexate

nCRP:

Native CRP

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NO:

Nitric oxide

NOD2:

Nucleotide-binding oligomerization domain containing 2

OCP:

Oral contraceptive pills

OR:

ODDs ratio

pANCA:

Perinuclear antineutrophil cytoplasmic antibodies

PTGER4:

Prostaglandin receptor 4

PTPN2:

Protein tyrosine phosphatase non-receptor type 2

SBFT:

Small bowel follow through

TGF:

Transforming growth factor

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TNFAIP3:

Tumor necrosis factor, alpha-induced protein 3

T-reg:

T-regulatory

UC:

Ulcerative colitis

WAS:

Wiskott–Aldrich syndrome

XLID:

X-linked immune dysregulation

References

  • Abraham C, Cho JH (2006) Functional consequences of NOD2 (CARD15) mutations. Inflamm Bowel Dis 12:641–650

    Article  PubMed  Google Scholar 

  • Annunziata ML, Caviglia R, Papparella LG et al (2012) Upper gastrointestinal involvement of Crohn’s disease: a prospective study on the role of upper endoscopy in the diagnostic work-up. Dig Dis Sci 57:1618–1623

    Article  PubMed  Google Scholar 

  • Annunziato F, Cosmi L, Santarlasci V et al (2007) Phenotypic and functional features of human Th17 cells. J Exp Med 204:1849–1861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Askling J, Dickman PW, Karlen P et al (2001) Family history as a risk factor for colorectal cancer in inflammatory bowel disease. Gastroenterology 120:1356–1362

    Article  CAS  PubMed  Google Scholar 

  • Baert F, D’Haens G, Peeters M et al (1999) Tumor necrosis factor alpha antibody (infliximab) therapy profoundly downregulates the inflammation in Crohn’s ileocolitis. Gastroenterology 116:22–28

    Article  CAS  PubMed  Google Scholar 

  • Barrett JC, Hansoul S, Nicolae DL et al (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40:955–962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bashir ME, Louie S, Shi HN, Nagler C (2004) Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy. J Immunol 172:6978–6987

    Article  CAS  PubMed  Google Scholar 

  • Baumeister D, Akhtar R, Ciufolini S, Pariante CM, Mondelli V (2016) Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, inetleukin-6 and tumour necrosis factor-α. Mol Psychiatry 21:642–649

    Article  CAS  PubMed  Google Scholar 

  • Bernstein C, Wajda A, Svenson L et al (2006) The epidemiology of inflammatory bowel disease in Canada: a population based study. Am J Gastroenterol 101:1559–1568

    Article  PubMed  Google Scholar 

  • Bitton A, Dobkin PL, Edwardes MD, Sewitch MJ, Meddings JB, Rawal S, Cohen A, Vermeire S, Dufresne L, Franchimont D, Wild GE (2008) Predicting relapse in Crohn’s disease: a biopsychosocial model. Gut 57:1386–1392. https://doi.org/10.1136/gut.2007.134817

    Article  CAS  PubMed  Google Scholar 

  • Boirivant M, Leoni M, Tariciotti D, Fais S, Squarcia O, Pallone F (1988) The clinical significance of serum C reactive protein levels in Crohn’s disease. Results of a prospective longitudinal study. J Clin Gastroenterol 10:401–405

    Article  CAS  PubMed  Google Scholar 

  • Boncler M, Watala C (2009) Regulation of cell function by isoforms of C-reactive protein: a comparative analysis. Acta Biochim Pol 56(1):17–31

    Article  CAS  PubMed  Google Scholar 

  • Both H, Torp-Pedersen K, Kreiner S et al (1983) Clinical appearance at diagnosis of ulcerative colitis and Crohn’s disease in a regional patient group. Scand J Gastroenterol 18:987–991

    Article  CAS  PubMed  Google Scholar 

  • Brentnall TA, Haggitt RC, Rabinovitch PS et al (1996) Risk and natural history of colonic neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis. Gastroenterology 110:331–338

    Article  CAS  PubMed  Google Scholar 

  • Bullock NR, Booth JC, Gibson GR (2004) Comparative composition of bacteria in the human intestinal microflora during remission and active ulcerative colitis. Curr Issues Intest Microbiol 5:59–64

    PubMed  Google Scholar 

  • Burton PR, Clayton DG, Cardon LR et al (2007) Association scan of 14,500 nonsynonymous SNPs in four diseases identifies auto immunity variants. Nat Genet 39:1329–1337

    Article  CAS  PubMed  Google Scholar 

  • Cadwell K, Liu JY, Brown SL et al (2008) A key role for autophagy and the autophagy gene Atg16L1 in mouse and human intestinal Paneth cells. Nature 456:259–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Canavan C, Abrams KR, Mayberry J (2006) Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn’s disease. Aliment Pharmacol Ther 23:1097–1104

    Article  CAS  PubMed  Google Scholar 

  • Cargill M, Schrodi SJ, Chang M et al (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80:273–290

    Article  CAS  PubMed  Google Scholar 

  • Castro M, Papadatou B, Baldassare M et al (2008) Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996–2003). Inflamm Bowel Dis 14:1246–1252

    Article  CAS  PubMed  Google Scholar 

  • Challacombe SJ, Tomsai TB (1980) Systemic tolerance and secretory immunity after oral imunization. J Exp Med 152:1459–1472

    Article  CAS  PubMed  Google Scholar 

  • Charpentier C, Salleron J, Savoye G et al (2014) Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study. Gut 63(3):423–432

    Article  PubMed  Google Scholar 

  • Cho JH, Brant SR (2011) Recent insights into the genetics of inflammatory bowel disease. Gastroenterology 140:1704–1712. https://doi.org/10.1053/j.gastro.2011.02.046

    Article  CAS  PubMed  Google Scholar 

  • Consigny Y, Modigliani R, Colombel JF, Dupas JL, Lémann M, Mary JY (2006) A simple biological score for predicting low risk of short term relapse in Crohn’s disease. Inflamm Bowel Dis 12:551–557

    Article  PubMed  Google Scholar 

  • Cooney R, Baker J, Brain O, Danis B, Pichulik T, Allan P et al (2010) NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med 16:90–97. https://doi.org/10.1038/nm.2069

    Article  CAS  PubMed  Google Scholar 

  • Cornish JA, Tan E, Teare J et al (2007) The effect of restorative proctocolectomy on sexual function, urinary function, fertility, pregnancy and delivery: a systematic review. Dis Colon Rectum 50:1128–1138

    Article  PubMed  Google Scholar 

  • Cosnes J, Gower-Rousseau C, Seksik P et al (2011) Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 140:1785–1794

    Article  PubMed  Google Scholar 

  • Derkx B, Taminiau J, Radema S et al (1993) Tumour-necrosis factor antibody treatment in Crohn’s disease. Lancet 342:173–174

    Article  CAS  PubMed  Google Scholar 

  • Dolwani S, Metzner M, Wassell JJ et al (2004) Diagnostic accuracy of faecal calprotectin estimation in prediction of abnormal small bowel radiology. Aliment Pharmacol Ther 20:615–621

    Article  CAS  PubMed  Google Scholar 

  • Du Clos TW (2000) Function of C-reactive protein. Ann Med 32(4):274–278

    Article  PubMed  Google Scholar 

  • Du Clos TW (2013) Pentraxins: structure, function and role in inflammation. ISRN Inflamm 2013:379040

    PubMed  PubMed Central  Google Scholar 

  • Du Clos TW, Mold C (2004) C-reactive protein: an activator of innate immunity and a modulator of adaptive immunity. Immunol Res 30(3):261–277

    Article  PubMed  Google Scholar 

  • Duerr RH, Taylor KD, Brant SR et al (2006a) A genome-wide association study identifies IL23r as an inflammatory bowel disease gene. Science 314:1461–1463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH (2006b) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Dullemen H, van Deventer S, Hommes D et al (1995) Treatment of Crohn’s disease with anti–tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 109:129–135

    Article  PubMed  Google Scholar 

  • Eckburg PB, Relman DA (2007) The role of microbes in Crohn’s disease. Clin Infect Dis 44:256–262

    Article  CAS  PubMed  Google Scholar 

  • Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA (2005) Diversity of the human intestinal microbial flora. Science 308:1635–1638

    Article  PubMed  PubMed Central  Google Scholar 

  • Economou M, Trikalinos TA, Loizou KT, Tsianos EV, Ioannidis JP (2004) Differential effects of NOD2 variants on Crohn’s disease risk and phenotype in diverse populations: a metaanalysis. Am J Gastroenterol 99:2393–2404

    Article  CAS  PubMed  Google Scholar 

  • Eisenhardt SU, Thiele JR, Bannasch H, Stark GB, Peter K (2009) C-reactive protein: how conformational changes influence inflammatory properties. Cell Cycle 8(23):3885–3892

    Article  CAS  PubMed  Google Scholar 

  • Elson CO, Cong Y, McCracken VJ, Dimmitt RA, Lorenz RG, Weaver CT (2005) Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota. Immunol Rev 206:260–276

    Article  PubMed  Google Scholar 

  • Elson CO, Cong Y, Weaver CT et al (2007) Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology 132:2359–2370

    Article  CAS  PubMed  Google Scholar 

  • Fagan EA, Dyck RF, Maton PN et al (1982a) Serum levels of C-reactive protein in Crohn’s disease and ulcerative colitis. Eur J Clin Invest 12:351–359

    Article  CAS  PubMed  Google Scholar 

  • Fagan EA, Dyck RF, Maton PN, Hodgson HJ, Chadwick VS, Petrie A, Pepys MB (1982b) Serum levels of C-reactive protein in Crohn’s disease and ulcerative colitis. Eur J Clin Invest 12:351–359

    Article  CAS  PubMed  Google Scholar 

  • Farmer R, Hawk W, Turnbull RBJ (1975) Clinical patterns in Crohn’s disease: a statistical study of 615 cases. Gastroenterology 68:627–635

    Article  CAS  PubMed  Google Scholar 

  • Franke A, Balschun T, Karlsen TH et al (2008) Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility. Nat Genet 40:1319–1323

    Article  CAS  PubMed  Google Scholar 

  • Fujino S, Andoh A, Bamba S et al (2003) Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52:65–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fuss IJ, Heller F, Boirivant M et al (2004) Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest 113:1490–1497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gelbmann CM (2000) Prediction of treatment refractoriness in ulcerative colitis and Crohn’s disease—do we have reliable markers? Inflamm Bowel Dis 6:123–131

    Article  CAS  PubMed  Google Scholar 

  • Girardin SE, Boneca IG, Viala J et al (2003) Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278:8869–8872

    Article  CAS  PubMed  Google Scholar 

  • Glocker E-O, Kotlarz D, Boztug K et al (2009) Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med 361:2033–2045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gosselink MP, Schouten WR, van Lieshout LM et al (2004) Delay of the first onset of pouchitis by oral intake of the probiotic strain Lactobacillus rhamnosus GG. Dis Colon Rectum 47:876–884

    Article  PubMed  Google Scholar 

  • Hanauer SB, Sandborn W, Practice Parameters Committee of the American College of Gastroenterology (2001) Management of Crohn’s disease in adults. Am J Gastroenterol 96:635–643

    Article  CAS  PubMed  Google Scholar 

  • Hedl M, Li J, Cho JH, Abraham C (2007) Chronic stimulation of Nod2 mediates tolerance to bacterial products. Proc Natl Acad Sci U S A 104:19440–19445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henriksen M, Jahnsen J, Lygren I et al (2008a) C-reactive protein: a predictive factor and marker of infl ammation in infl ammatory bowel disease. Results from a prospective population-based study. Gut 57:1518–1523

    Article  CAS  PubMed  Google Scholar 

  • Henriksen M, Jahnsen J, Lygren I, Stray N, Sauar J, Vatn MH, Moum B (2008b) C-reactive protein: a predictive factor and marker of inflammation in inflammatory bowel disease. Results from a prospective population-based study. Gut 57:1518–1523

    Article  CAS  PubMed  Google Scholar 

  • Holmén N, Lundgren A, Lundin S et al (2006) Functional CD4+CD25 high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity. Inflamm Bowel Dis 12:447–456

    Article  PubMed  Google Scholar 

  • Hölttä V, Klemetti P, Sipponen T et al (2008) IL-23/IL-17 immunity as a hallmark of Crohn’s disease. Inflamm Bowel Dis 14:1175–1184

    Article  PubMed  Google Scholar 

  • Hue S, Ahern P, Buonocore S et al (2006) 61. Interleukin-23 drives innate and T cellmediated intestinal inflammation. J Exp Med 203:2473–2483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411:599–603

    Article  CAS  PubMed  Google Scholar 

  • Inohara N, Ogura Y, Fontalba A et al (2003) Host recognition of bacterial muramyl dipeptide mediated through NOD2: implications for Crohn’s disease. J Biol Chem 278:5509–5512

    Article  CAS  PubMed  Google Scholar 

  • Izcue A, Coombes JL, Powrie F (2006) Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol Rev 212:256–271

    Article  CAS  PubMed  Google Scholar 

  • Jacobsen B, Fallingborg J, Rasmussen H et al (2006) Increase in incidence and prevalence of inflammatory bowel disease in northern Denmark: a population-based study, 1978–2002. Gastroenterol Hepatol 18:601–606

    Google Scholar 

  • Jaensson E, Uronen-Hansson H, Pabst O et al (2008) Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J Exp Med 205:2139–2149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jess T, Riis L, Vind I et al (2007) Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: a population based study from Copenhagen, Denmark. Inflamm Bowel Dis 13:481–489

    Article  PubMed  Google Scholar 

  • Jiang L, Xia B, Li J et al (2006) Retrospective survey of 452 patients with inflammatory bowel disease in Wuhan city, central China. Inflamm Bowel Dis 12:212–217

    Article  PubMed  Google Scholar 

  • Jones J, Loftus EV, Panaccione R, Chen LS, Peterson S, McConnell J, Baudhuin L, Hanson K, Feagan BG, Harmsen SW, Zinsmeister AR, Helou E, Sandborn WJ (2008) Relationships between disease activity and serum and fecal biomarkers in patients with Crohn’s disease. Clin Gastroenterol Hepatol 6:1218–1224

    Article  PubMed  Google Scholar 

  • Jürgens M, Mahachie John JM, Cleynen I, Schnitzler F, Fidder H, van Moerkercke W, Ballet V, Noman M, Hoffman I, van Assche G, Rutgeerts PJ, van Steen K, Vermeire S (2011) Levels of C-reactive protein are associated with response to infliximab therapy in patients with Crohn’s disease. Clin Gastroenterol Hepatol 9:421–427.e1

    Article  PubMed  CAS  Google Scholar 

  • Kappelman M, Rifas-Shiman S, Kleinman K et al (2007) The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol 5:1424–1429

    Article  PubMed  Google Scholar 

  • Karmiris K, Paintaud G, Noman M, Magdelaine-Beuzelin C, Ferrante M, Degenne D, Claes K, Coopman T, Van Schuerbeek N, Van Assche G, Vermeire S, Rutgeerts P (2009) Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn’s disease. Gastroenterology 137:1628–1640

    Article  CAS  PubMed  Google Scholar 

  • Karoui S, Ouerdiane S, Serghini M, Jomni T, Kallel L, Fekih M, Boubaker J, Filali A (2007) Correlation between levels of C-reactive protein and clinical activity in Crohn’s disease. Dig Liver Dis 39:1006–1010

    Article  CAS  PubMed  Google Scholar 

  • Khan KJ, Ullman TA, Ford AC, Abreu MT, Abadir A, Marshall JK, Talley NJ, Moayyedi P (2011) Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol 106:661–673

    Article  CAS  PubMed  Google Scholar 

  • Kim PH, Kagnoff MF (1990) Transforming growth factor beta 1 increases IgA isotype switching at the clonal level. J Immunol 145:3773–3778

    CAS  PubMed  Google Scholar 

  • Kobayashi KS, Chamaillard M, Ogura Y et al (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307:731–734

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi T, Okamoto S, Hisamatsu T et al (2008) IL-23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn’s disease. Gut 57:1682–1689

    Article  CAS  PubMed  Google Scholar 

  • Koelewijn CL, Schwartz MP, Samsom M, Oldenburg B (2008) C-reactive protein levels during a relapse of Crohn’s disease are associated with the clinical course of the disease. World J Gastroenterol 14:85–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kunimoto DY, Ritzel M, Tsang M (1992) The roles of IL-4, TGF-beta and LPS in IgA switching. Eur Cytokine Netw 3:407–415

    CAS  PubMed  Google Scholar 

  • Langholz E, Munkholm P, Davidsen M et al (1994) Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology 107:3–11

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Mo JH, Katakura K et al (2006) Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol 8:1327–1336

    Article  CAS  PubMed  Google Scholar 

  • Lesage S, Zouali H, Cézard JP et al (2002) CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet 70:845–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis J, Deren J, Lichtenstein G (1999) Cancer risk in patients with inflammatory bowel disease. Gastroenterol Clin North Am 28:459–477. x

    Article  CAS  PubMed  Google Scholar 

  • Lodes MJ, Cong Y, Elson CO, Mohamath R, Landers CJ, Targan SR, Fort M, Hershberg RM (2004) Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest 113:1296–1306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loftus C, Loftus EVJ, Harmsen W et al (2007) Update on the incidence and prevalence of Crohn’s disease and ulcerative colitis in Olmsted County, Minnesota, 1940-2000. Inflamm Bowel Dis 13:254–261

    Article  PubMed  Google Scholar 

  • Makita S, Kanai T, Oshima S et al (2004) CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells. J Immunol 173:3119–3130

    Article  CAS  PubMed  Google Scholar 

  • Mattingly JA, Waksman BH (1978) Immunologic suppression after oral administration of antigen. I. Specific suppressor cells formed rat Peyer’s patches after oral administration. J Immunol 121:1878–1883

    CAS  PubMed  Google Scholar 

  • Mayer L, Sperber K, Chan L et al (2001) Oral tolerance to protein antigens. Allergy 56(Suppl 67):12–15

    Article  PubMed  Google Scholar 

  • Mitsuyama K, Niwa M, Takedatsu H, Yamasaki H, Kuwaki K, Yoshioka S, Yamauchi R, Fukunaga S, Torimura T (2016) Antibody markers in the diagnosis of inflammatory bowel disease. World J Gastroenterol 22:1304–1310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG (2012) Increasing incidence and prevalence of the inflammatory bowel disease with time, based on systematic review. Gastroenterology 142(1):46–54. https://doi.org/10.1053/j.gastro.2011.10.001

  • Mora JR, Bono MR, Manjunath N et al (2003) Selective imprinting of gut-homing T cells by Peyer’s patch dendritic cells. Nature 424:88–93

    Article  CAS  PubMed  Google Scholar 

  • Mosli MH, Zou G, Garg SK, Feagan SG, MacDonald JK, Chande N, Sandborn WJ, Feagan BG (2015) C-reactive protein, fecal calprotectin, and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients: a systematic review and meta-analysis. Am J Gastroenterol 110:802–819. quiz 820

    Article  PubMed  Google Scholar 

  • Mucida D, Park Y, Kim G et al (2007) Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317:256–256

    Article  CAS  PubMed  Google Scholar 

  • Nedjic J, Aichinger M, Emmerich JMizushima N, Klein L (2008) Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 455:396–400

    Article  CAS  PubMed  Google Scholar 

  • Nerich V, Monnet E, Etienne A et al (2006) Geographical variations of inflammatory bowel disease in France: a study based on national health insurance data. Inflamm Bowel Dis 12:218–226

    Article  PubMed  Google Scholar 

  • Nerich V, Jantchou P, Boutron-Ruault MC et al (2011) Low exposure to sunlight is a risk factor for Crohn’s disease. Aliment Pharmacol Ther 33:940–945

    Article  CAS  PubMed  Google Scholar 

  • Nguyen DD, Maillard MH, Cotta-de-Almeida V et al (2007) Lymphocyte-dependent and Th2 cytokine-associated colitis in mice deficient in Wiskott-Aldrich syndrome protein. Gastroenterology 133:1188–1197

    Article  CAS  PubMed  Google Scholar 

  • Oikonomou KA, Kapsoritakis AN, Theodoridou C et al (2012) Neutrophil gelatinase-associated lipocalin (NGAL) in infl ammatory bowel disease: association with pathophysiology of inflammation, established markers, and disease activity. J Gastroenterol 47:519–530

    Article  CAS  PubMed  Google Scholar 

  • Olson TS, Bamias G, Naganuma M et al (2004) Expanded B cell population blocks regulatory T cells and exacerbates ileitis in a murine model of Crohn disease. J Clin Invest 114:389–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orchard TR, Wordsworth BP, Jewell DP (1998) Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history. Gut 42:387–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peterson DA, Gordon JI (2005) Host-bacterial mutualism in the human intestine. Science 307:1915–1920

    Article  PubMed  CAS  Google Scholar 

  • Peyrin-Biroulet L, Loftus EV Jr, Colombel JF et al (2011) Longterm complications, extraintestinal manifestations, and mortality in adult Crohn’s disease in population-based cohorts. Inflamm Bowel Dis 17:471–478

    Article  PubMed  Google Scholar 

  • Pickard KM, Bremner AR, Gordon JN, MacDonald TT (2004) Microbial-gut interactions in health and disease. Immune Respon Best Pract Res Clin Gastroenterol 18:271–285

    Article  CAS  Google Scholar 

  • Potempa LA, Maldonado BA, Laurent P, Zemel ES, Gewurz H (1983) Antigenic, electrophoretic and binding alterations of human C-reactive protein modified selectively in the absence of calcium. Mol Immunol 20(11):1165–1175

    Article  CAS  PubMed  Google Scholar 

  • Potempa LA, Siegel JN, Fedel BA, Potempa RT, Gewurz H (1987) Expression, detection and assay of a neoantigen (Neo-CRP) associated with a free, human C-reactive protein subunit. Mol Immunol 24(5):531–541

    Article  CAS  PubMed  Google Scholar 

  • Quigley EM, Quera R (2006) Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastroenterology 130:S78–S90

    Article  CAS  PubMed  Google Scholar 

  • Rajaratnam SG, Eglinton TW, Hider P et al (2011) Impact of ileal pouch-anal anastomosis on female fertility: Meta-analysis and systematic review. Int J Colorectal Dis 26:1365–1374

    Article  PubMed  Google Scholar 

  • Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R (2004) Recognition of commensal microflora by tolllike receptors is required for intestinal homeostasis. Cell 118:229–241

    Article  CAS  PubMed  Google Scholar 

  • Rao SS, Holdsworth CD, Read NW (1988) Symptoms and stool patterns in patients with ulcerative colitis. Gut 29:342–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rutter M, Saunders B, Wilkinson K et al (2004) Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 126:451–459

    Article  PubMed  Google Scholar 

  • Saitoh T, Fujita N, Jang MH et al (2008) Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature 456:264–268

    Article  CAS  PubMed  Google Scholar 

  • Sandle GI, Higgs N, Crowe P et al (1990) Cellular basis for defective electrolyte transport in inflamed human colon. Gastroenterology 99:97–105

    Article  CAS  PubMed  Google Scholar 

  • Saruta M, Yu QT, Avanesyan A, Fleshner PR, Targan SR, Papadakis KA (2007) Phenotype and effector function of CC chemokine receptor 9-expressing lymphocytes in small intestinal Crohn’s disease. J Immunol 178:3293–3300

    Article  CAS  PubMed  Google Scholar 

  • Saverymuttu SH, Hodgson HJ, Chadwick VS, Pepys MB (1986) Differing acute phase responses in Crohn’s disease and ulcerative colitis. Gut 27:809–813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schoepfer AM, Beglinger C, Straumann A et al (2013) Fecal calprotectin more accurately refl ects endoscopic activity of ulcerative colitis than the Lichtiger Index, C-reactive protein, platelets, hemoglobin, and blood leukocytes. Inflamm Bowel Dis 19:332–341

    Article  PubMed  Google Scholar 

  • Shine B, Berghouse L, Jones JE et al (1985) C-reactive protein as an aid in the diff erentiation of functional and infl ammatory bowel disorders. Clin Chim Acta 148:105–109

    Article  CAS  PubMed  Google Scholar 

  • Siewert C, Lauer U, Cording S et al (2008) Experience-driven development: effector/memory-like alphaE+Foxp3+ regulatory T cells originate from both naive T cells and naturally occurring naive-like regulatory T cells. J Immunol 180:146–155

    Article  CAS  PubMed  Google Scholar 

  • Solem CA, Loftus EV, Tremaine WJ, Harmsen WS, Zinsmeister AR, Sandborn WJ (2005) Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis 11:707–712

    Article  PubMed  Google Scholar 

  • Strobel SS (1996) Neonatal oral tolerance. Ann N Y Acad Sci 778:88–102

    Article  CAS  PubMed  Google Scholar 

  • Targan S, Hanauer S, van Deventer S et al (1997) 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 337:1029–1035

    Article  CAS  PubMed  Google Scholar 

  • Tibble J, Teahon K, Thjodleifsson B et al (2000) A simple method for assessing intestinal inflammation in Crohn’s disease. Gut 47:506–513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tilakaratne S, Lemberg DA, Leach ST, Day AS (2010) C-reactive protein and disease activity in children with Crohn’s disease. Dig Dis Sci 55:131–136

    Article  CAS  PubMed  Google Scholar 

  • Tillett WS, Francis T (1930) Serological reactions in pneumonia with a non-protein somatic fraction of pneumococcus. J Exp Med 52:561–571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Titus RG, Chiller JM (1981) Orally induced tolerance. Definition at the cellular level. Int Arch Allergy Appl Immunol 65:323–338

    Article  CAS  PubMed  Google Scholar 

  • Travis SP, Farrant JM, Ricketts C, Nolan DJ, Mortensen NM, Kettlewell MG, Jewell DP (1996) Predicting outcome in severe ulcerative colitis. Gut 38:905–910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Turnbaugh PJ, Hamady M, Yatsunenko T et al (2009) A core gut microbiome in obese and lean twins. Nature 457:480–484

    Article  CAS  PubMed  Google Scholar 

  • Uhlig HH, Schwerd T, Koletzko S, Shah N, Kammermeier J, Elkadri A et al (2014) The diagnostic approach to monogenic very early onset inflammatory bowel disease. Gastroenterology 147(5):990–1007. https://doi.org/10.1053/j.gastro.2014.07.023

    Article  PubMed  Google Scholar 

  • Vargas EJ, Ramos Rivers CM, Regueiro M, Baidoo L, Barrie A, Schwartz M, Swoger JM, Coates M, Dunn MA, Dudekula A, Binion DG (2013) Silent Crohn’s disease: elevated c reactive protein in asymptomatic patients and risk of subsequent hospitalization. Gastroenterology 144:S-102

    Article  Google Scholar 

  • Vavricka SR, Spigaglia SM, Rogler G et al (2012) Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease. Inflamm Bowel Dis 18:496–505

    Article  PubMed  Google Scholar 

  • Velázquez P, Wei B, Braun J (2005) Surveillance B lymphocytes and mucosal immuno regulation. Springer Semin Immunopathol 26:453–462

    Article  PubMed  Google Scholar 

  • Vermeire S, Van Assche G, Rutgeerts P (2005) The role of C-reactive protein as an inflammatory marker in gastrointestinal diseases. Nat Clin Pract Gastroenterol Hepatol 2:580–586

    Article  CAS  PubMed  Google Scholar 

  • Vijay-Kumar M, Sanders CJ, Taylor RT et al (2007) Deletion of TLR5 results in spontaneous colitis in mice. J Clin Invest 117:3909–3921

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Liu XP, Zhao ZB et al (2011) Expression of CD4+ forkhead box P3 (FOXP3)+ regulatory T cells in inflammatory bowel disease. Dig Dis Sci 12:286–294

    Article  CAS  Google Scholar 

  • Weiner HL, Mayer LF (1996) Oral tolerance: Mechanisms and applications. Introduction. Ann N Y Acad Sci 778:xiii–xviii

    Article  CAS  PubMed  Google Scholar 

  • Whitacre CC, Gienapp IE, Meyer A et al (1996) Treatment of autoimmune disease by oral tolerance to autoantigens. Clin Immunol Immunopathol 80:S31–S39

    Article  CAS  PubMed  Google Scholar 

  • Wu L, Estrada O, Zaborina O et al (2005) Recognition of host immune activation by Pseudomonas aeruginosa. Science 309:774–777

    Article  CAS  PubMed  Google Scholar 

  • Xiao BG, Link H (1997) Mucosal tolerance: a two-edged sword to prevent and treat autoimmune diseases. Clin Immunol Immunopathol 85:119–128

    Article  CAS  PubMed  Google Scholar 

  • Yang JY, Kim MS, Kim E, Cheon JH, Lee YS, Kim Y, Lee SH, Seo SU, Shin SH, Choi SS, Kim B, Chang SY, Ko HJ, Bae JW, Kweon MN (2016) Enteric viruses ameliorate gut inflammation via Toll-like receptor 3 and Toll-like receptor 7-mediated interferon-beta production. Immunity 44:889–900

    Article  CAS  PubMed  Google Scholar 

  • Yantiss RK, Odze RD (2007) Pitfalls in the interpretation of nonneoplastic mucosal biopsies in inflammatory bowel disease. Am J Gastroenterol 102:890–904

    Article  PubMed  Google Scholar 

  • Yen D, Cheung J, Scheerens H et al (2006) IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest 116:1310–1316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Malakar, S. (2020). C-Reactive Protein in Inflammatory Bowel Disease. In: Ansar, W., Ghosh, S. (eds) Clinical Significance of C-reactive Protein. Springer, Singapore. https://doi.org/10.1007/978-981-15-6787-2_3

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