Prof Sir Mark Pepys

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Personal Profile

Name: Mark Pepys Email: m.pepys@ucl.ac.uk
Title: Prof Sir Tel: 020 7433 2801
Department: Inflammation Fax: 020 7433 2803
Position: Principal Clinical Research Associate Address: Centre for Amyloidosis & Acute Phase Proteins, UCL Division of Medicine, Royal Free Campus, London, NW3 2PF
Research Domain: Basic Life Sciences, Cardiometabolic Science, Experimental Medicine, Infection, Immunology & Inflammation, Neuroscience, Personalised Medicine Web Page: Personal Web Page

Profile

Research Description

After his seminal discovery in 1972 of the role of complement in the induction of antibody production Pepys has mostly worked on amyloid and acute phase proteins. He has illuminated the pathogenesis and natural history of systemic amyloidosis, transforming diagnosis of this fatal disease, and improving management and survival. He has also elucidated the structural properties, function and clinical significance of serum amyloid P component (SAP) and C reactive protein (CRP). He first identified these proteins as therapeutic targets, and has developed new drugs aimed at them.
His invention of in vivo scintigraphy with radiolabelled SAP enabled systemic amyloidosis for the first time to be safely, non invasively diagnosed and quantitatively monitored. This revolutionised understanding of the natural history of amyloidosis and its response to therapy, guiding radical therapeutic developments, especially regarding the crucial importance of reducing the abundance of amyloid fibril protein precursors. Some fatal hereditary amyloidoses are now curable by liver transplantation, and the prognosis of acquired amyloidosis has greatly improved. Pepys has discovered many of the mutations responsible for hereditary amyloidosis, including the first mutations in the human lysozyme gene. He showed that amyloidogenic lysozyme variants are less stable than wild type lysozyme and developed a widely accepted general model of amyloid fibrillogenesis. His detailed phenotypic characterisation of hereditary amyloidoses has improved investigation and management of systemic amyloidosis in general.
Pepys’s first suggestion of small molecule therapy for amyloidosis (1984) led eventually to his novel SAP targeting drug, CPHPC, a bis(D-proline) compound reported in Nature in 2002, which the American Chemical Society recognised as one of the medicinal chemistry annual highlights. This small molecule palindromic ligand cross links pairs of circulating SAP molecules, triggering their immediate clearance from the circulation and depleting SAP from systemic amyloid deposits and from the brain in Alzheimer’s disease. He has demonstrated that the drug may have clinical efficacy in hereditary amyloidosis. The capacity of the drug to deplete SAP from the brain offers an exciting new therapeutic prospect for Alzheimer’s disease, soon to be tested in a clinical trial. His invention of the combination of CPHPC and antibody to serum amyloid P component for treatment of systemic amyloidosis is being developed in collaboration with GlaxoSmithKline and is now being tested in the first patients. GSK are also collaborating on his new small molecule approaches to treatment of transthyretin amyloidosis.
Pepys’s demonstration that CRP increases ischaemic myocardial and cerebral damage in vivo, was the first validation of CRP as a potential therapeutic target. His success in targeting SAP enabled his rational design of bis phosphocholine hexane, the first specific inhibitor of CRP, reported in Nature in 2006. Development of more medicinal CRP inhibitor compounds for treatment of conditions associated with greatly increased CRP production is in progress with MRC support. Pepys previously played a leading role in establishing the routine use of CRP testing in clinical practice, and produced the WHO International Immunoassay Reference Standards for CRP, serum amyloid A protein, and thyroxine binding globulin.


Research Activities

Acute phase proteins

Amyloidosis

Drug discovery and development

Pentraxins

Education Description

UCL Collaborators

Dr Paul Simons; Dr Alun Coker

External Collaborators

Publications

    2014

    • Kolstoe SE, Jenvey MC, Purvis A, Light ME, Thompson D, Hughes P, Pepys MB, Wood SP (2014). Interaction of serum amyloid P component with hexanoyl bis(D-proline) (CPHPC).. Acta Crystallogr D Biol Crystallogr, 70(Pt 8), 2232 - 2240. doi:10.1107/S1399004714013455
    • Mangione PP, Porcari R, Gillmore JD, Pucci P, Monti M, Porcari M, Giorgetti S, Marchese L, Raimondi S, Serpell LC, Chen W, Relini A, Marcoux J, Clatworthy IR, Taylor GW, Tennent GA, Robinson CV, Hawkins PN, Stoppini M, Wood SP, Pepys MB, Bellotti V (2014). Proteolytic cleavage of Ser52Pro variant transthyretin triggers its amyloid fibrillogenesis.. Proc Natl Acad Sci U S A, 111(4), 1539 - 1544. doi:10.1073/pnas.1317488111
    • Dettmar AK, Binder E, Greiner FR, Liebau MC, Kurschat CE, Jungraithmayr TC, Saleem MA, Schmitt C-P, Feifel E, Orth-Hoeller D, Kemper MJ, Pepys M, Wuerzner R, Oh J (2014). Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component. INFECTION AND IMMUNITY, 82(5), 1872 - 1879. doi:10.1128/IAI.01591-14
    • Pepys-Vered ME, Pepys MB (2014). Targeted Treatment for Amyloidosis. ISRAEL MEDICAL ASSOCIATION JOURNAL, 16(5), 277 - 280.
    • Greenland P, Pepys M (2014). Attention to Detail in the Selection of Words in Epidemiologic Research Reports. AMERICAN JOURNAL OF EPIDEMIOLOGY, 179(7), 795 - 796. doi:10.1093/aje/kwu008
    • Simons JP, Loeffler JM, Al-Shawi R, Ellmerich S, Hutchinson WL, Tennent GA, Petrie A, Raynes JG, de Souza JB, Lawrence RA, Read KD, Pepys MB (2014). C-reactive protein is essential for innate resistance to pneumococcal infection.. Immunology, , - . doi:10.1111/imm.12266

    2013

    • Lane T, Wassef NL, Poole S, Mistry Y, Lachmann H, Gillmore J, Hawkins PN, Pepys MB (2013). Infusion of Pharmaceutical Grade Natural Human C Reactive Protein is not Pro Inflammatory in Healthy Adult Human Volunteers.. Circ Res, , - . doi:10.1161/CIRCRESAHA.114.302770
    • Sofat R, Mangione PP, Gallimore JR, Hakobyan S, Hughes TR, Shah T, Goodship T, D'Aiuto F, Langenberg C, Wareham N, Morgan BP, Pepys MB, Hingorani AD (2013). Distribution and determinants of circulating complement factor H concentration determined by a high-throughput immunonephelometric assay.. J Immunol Methods, 390(1-2), 63 - 73. doi:10.1016/j.jim.2013.01.009
    • Mangione PP, Esposito G, Relini A, Raimondi S, Porcari R, Giorgetti S, Corazza A, Fogolari F, Penco A, Goto . Y, Lee YH, Yagi H, Cecconi C, Naqvi MM, Gillmore JD, Hawkins PN, Chiti F, Rolandi R, Taylor GW, Pepys MB, Stoppini M, Bellotti V V (2013). Structure, folding dynamics and amyloidogenesis of Asp76Asn β2-microglobulin: roles of shear flow, hydrophobic surfaces and α crystallin.. J Biol Chem, , - .
    • Dettmar AK, Binder E, Liebau MC, Jungraithmayr TC, Saleem MA, Schmitt CP, Kemper MJ, Pepys M, Wuerzner R, Oh J (2013). Human Serum Amyloid P Decreases Shigatoxin 2 Induced Activation of Mitogen Activated Protein Kinases and Apoptosis in Human Podocytes. PEDIATRIC NEPHROLOGY, 28(8), 1350 - 1351.
    • Campbell-Washburn AE, Price AN, Ellmerich S, Simons JP, Al-Shawi R, Kalber TL, Ghatrora R, Hawkins PN, Moon JC, Ordidge RJ, Pepys MB, Lythgoe MF (2013). Monitoring systemic amyloidosis using MRI measurements of the extracellular volume fraction.. Amyloid, 20(2), 93 - 98. doi:10.3109/13506129.2013.787984
    • Simons JP, Al-Shawi R, Ellmerich S, Speck I, Aslam S, Hutchinson WL, Mangione PP, Disterer P, Gilbertson JA, Hunt T, Millar DJ, Minogue S, Bodin K, Pepys MB, Hawkins PN (2013). Pathogenetic mechanisms of amyloid A amyloidosis.. Proc Natl Acad Sci U S A, , - . doi:10.1073/pnas.1306621110

    2012

    • Pepys MB, Gallimore JR, Lloyd J, Li Z, Graham D, Taylor GW, Ellmerich S, Mangione PP, Tennent GA, Hutchinson WL, Millar DJ, Bennett G, More J, Evans D, Mistry Y, Poole S, Hawkins PN (2012). Isolation and characterization of pharmaceutical grade human pentraxins, serum amyloid P component and C-reactive protein, for clinical use.. J Immunol Methods, 384(1-2), 92 - 102. doi:10.1016/j.jim.2012.07.013
    • Pepys MB (2012). Invasive candidiasis: new insights presaging new therapeutic approaches?. J Infect Dis, 206(9), 1339 - 1341. doi:10.1093/infdis/jis521
    • Valleix S, Gillmore JD, Bridoux F, Mangione PP, Dogan A, Nedelec B, Boimard M, Touchard G, Goujon JM, Lacombe C, Lozeron P, Adams D, Lacroix C, Maisonobe T, Planté-Bordeneuve V, Vrana JA, Theis JD, Giorgetti S, Porcari R, Ricagno S, Bolognesi M, Stoppini M, Delpech M, Pepys MB, Hawkins PN, Bellotti V (2012). Hereditary systemic amyloidosis due to Asp76Asn variant β2-microglobulin.. N Engl J Med, 366(24), 2276 - 2283. doi:10.1056/NEJMoa1201356
    • Kaptoge S, Di Angelantonio E, Pennells L, Wood AM, White IR, Gao P, Walker M, Thompson A, Sarwar N, Caslake M, Butterworth AS, Amouyel P, Assmann G, Bakker SJL, Barr ELM, Barrett-Connor E, Benjamin EJ, Bjorkelund C, Brenner H, Brunner E, Clarke R, Cooper JA, Cremer P, Cushman M, Dagenais GR, Sr DRB, Dankner R, Davey-Smith G, Deeg D, Dekker JM, Engstrom G, Folsom AR, Fowkes FGR, Gallacher J, Gaziano JM, Giampaoli S, Gillum RF, Hofman A, Howard BV, Ingelsson E, Iso H, Jorgensen T, Kiechl S, Kitamura A, Kiyohara Y, Koenig W, Kromhout D, Kuller LH, Lawlor DA, Meade TW, Nissinen A, Nordestgaard BG, Onat A, Panagiotakos DB, Psaty BM, Rodriguez B, Rosengren A, Salomaa V, Kauhanen J, Salonen JT, Shaffer JA, Shea S, Ford I, Stehouwer CDA, Strandberg TE, Tipping RW, Tosetto A, Wassertheil-Smoller S, Wennberg P, Westendorp RG, Whincup PH, Wilhelmsen L, Woodward M, Lowe GDO, Wareham NJ, Khaw K-T, Sattar N, Packard CJ, Gudnason V, Ridker PM, Pepys MB, Thompson SG, Danesh J, Factors ER (2012). C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction. NEW ENGLAND JOURNAL OF MEDICINE, 367(14), 1310 - 1320. doi:10.1056/NEJMoa1107477
    • Lachmann HJ, Gillmore JD, Wechalekar AD, Gibbs SD, Pinney JH, Rowczenio DM, Trojer H, Lane T, Venner CP, Banypersad SM, Gilbertson JA, Hunt FT, Gopaul D, Hutt DF, Wassef N, Pepys MB, Hawkins PN (2012). A 20 YEAR SINGLE CENTRE EXPERIENCE OF AA AMYLOIDOSIS DEMONSTRATING CHANGES IN ITS EPIDEMIOLOGY. ANNALS OF THE RHEUMATIC DISEASES, 71, 283 - 284.

    2011

    • Wensley F, Gao P, Burgess S, Kaptoge S, Di Angelantonio E, Shah T, Engert JC, Clarke R, Davey-Smith G, Nordestgaard BG (2011). Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data. BMJ, 342, d548 - . doi:10.1136/bmj.d548
    • Millar DJ, Hutchinson WL, Pepys MB (2011). Immunoradiometric assay for human serum amyloid P component. J Immunol Methods, 371(1-2), 18 - 24. doi:10.1016/j.jim.2011.06.010
    • Campbell AE, Price AN, Ellmerich S, Simons P, Al-Shawi R, Hawkins PN, Ordidge RJ, Pepys MB, Moon JC, Lythgoe MF (2011). Equilibrium contrast CMR for the detection of amyloidosis in mice. doi:10.1186/1532-429X-13-S1-O60
    • Mikolajek H, Kolstoe SE, Pye VE, Mangione P, Pepys MB, Wood SP (2011). Structural basis of ligand specificity in the human pentraxins, C-reactive protein and serum amyloid P component. J Mol Recognit, 24(2), 371 - 377. doi:10.1002/jmr.1090

    2010

    • Hutchinson WL, Herbert J, Pepys MB (2010). Serum amyloid P component is a constituent of normal adult mammalian glomeruli.
    • Carlucci F, Cook HT, Garg A, Pepys MB, Botto M (2010). Lack of effect of a single injection of human C-reactive protein on murine lupus or nephrotoxic nephritis. Arthritis Rheum, 62(1), 245 - 249. doi:10.1002/art.27232
    • Bodin K, Ellmerich S, Kahan MC, Tennent GA, Loesch A, Gilbertson JA, Hutchinson WL, Mangione PP, Gallimore JR, Millar DJ, Minogue S, Dillon AP, Taylor GW, Bradwell AR, Petrie A, Gilmore JD, Bellotti V, Botto M, Hawkins PN, Pepys MB (2010). Antibodies to human serum amyloid P component eliminate visceral amyloid deposits. Nature, 468(7320), 93 - 97. doi:10.1038/nature09494
    • Sattianayagam PT, Rowczenio DM, Gibbs SDJ, Trojer H, Russell TL, Pinney JH, Lachmann HJ, Wechalekar AD, Hawkins PN, Pepys MB, Gilbertson JA, Hunt T, Gillmore JD (2010). Natural history of hereditary lysozyme amyloidosis.
    • Mangione PP, Bellotti V, Deroo S, Taylor GW, McCammon MG, Robinson CV, Tennent GA, Smith MD, Morrison AJ, Cobb AJA, Coyne A, Ley SV, Wood SP, Pepys MB (2010). Novel palindromic ligands cementing the native quaternary structure of transthyretin.
    • Simons P, Al-Shawi R, Ellmerich S, Slamova I, Bodin K, Minogue S, Pepys MB, Hawkins PN (2010). Controllable expression of SAA in transgenic mice: a refined model of systemic amyloidosis.
    • Kolstoe SE, Mangione PP, Bellotti V, Taylor GW, Tennent GA, Deroo S, Morrison AJ, Cobb AJ, Coyne A, McCammon MG, Warner TD, Mitchell J, Gill R, Smith MD, Ley SV, Robinson CV, Wood SP, Pepys MB (2010). Trapping of palindromic ligands within native transthyretin prevents amyloid formation. Proc Natl Acad Sci U S A, 107(47), 20483 - 20488. doi:10.1073/pnas.1008255107
    • Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, Danesh J (2010). C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet, 375(9709), 132 - 140. doi:10.1016/S0140-6736(09)61717-7
    • Tennent GA, Pepys MB (2010). Binding by serum amyloid P component (SAP) is a pathognomonic feature of genuine amyloid fibrils.
    • Kolstoe S, Morrison AJ, Cobb AJA, Coyne A, Gill R, Smith MD, Ley SV, Wood SP, Pepys MB (2010). Targeting transthyretin - X-ray crystallography and rational drug design.
    • Gillmore JD, Tennent GA, Hutchinson WL, Gallimore JR, Lachmann HJ, Goodman HJ, Offer M, Millar DJ, Petrie A, Hawkins PN, Pepys MB (2010). Sustained pharmacological depletion of serum amyloid P component in patients with systemic amyloidosis. Brit J Haematol, 148(5), 760 - 767. doi:10.1111/j.1365-2141.2009.08036.x
    • Tennent GA, Loesch A, Kahan M, Bodin K, Ellmerich S, Minogue S, Pepys MB (2010). Macrophage dependent elimination of amyloid following treatment with anti-SAP antibody.

    2009

    • Kolstoe SE, Ridha BH, Bellotti V, Wang N, Robinson CV, Crutch SJ, Keir G, Kukkastenvehmas R, Gallimore JR, Hutchinson WL, Hawkins PN, Wood SP, Rossor MN, Pepys MB (2009). Molecular dissection of Alzheimer's disease neuropathology by depletion of serum amyloid P component. Proc Natl Acad Sci U S A, 106(18), 7619 - 7623. doi:10.1073/pnas.0902640106
    • Danesh J, Pepys MB (2009). C-reactive protein and coronary disease: is there a causal link?. Circulation, 120(21), 2036 - 2039. doi:10.1161/CIRCULATIONAHA.109.907212
    • Pepys MB (2009). A molecular correlate of clinicopathology in transthyretin amyloidosis. J Pathol, 217(1), 1 - 3.
    • Pepys MB (2009). The Allergy Archives: Pioneers and Milestones. Jack Pepys (May 15, 1914 - September 9, 1996): a personal recollection. J Allergy Clin Immunol, 123(3), 718 - 720.

    2008

    • Casas JP, Shah T, Hingorani AD, Danesh J, Pepys MB (2008). C-reactive protein and coronary heart disease: a critical review. J Intern Med, 264(4), 295 - 314.
    • Tennent GA, Hutchinson WL, Kahan MC, Hirschfield GM, Gallimore JR, Lewin J, Sabin CA, Dhillon AP, Pepys MB (2008). Transgenic human CRP is not pro-atherogenic, pro-atherothrombotic or pro-inflammatory in apoE-/- mice. Atherosclerosis, 196(1), 248 - 255. doi:10.1016/j.atherosclerosis.2007.05.010
    • Hakobyan S, Harris CL, van den Berg CW, Fernandez-Alonso MC, de Jorge EG, de Cordoba SR, Rivas G, Mangione P, Pepys MB, Morgan BP (2008). Complement factor H binds to denatured rather than to native pentameric C-reactive protein. J Biol Chem, 283(45), 30451 - 30460.
    • Pepys MB (2008). C-reactive protein is neither a marker nor a mediator of atherosclerosis. Nat Clin Pract Nephrol, 4(5), 234 - 235.

    2007

    • James LC, Jones PC, McCoy A, Tennent GA, Pepys MB, Famm K, Winter G (2007). β-edge interactions in a pentadecameric human antibody Vκ domain. J Mol Biol, 367(3), 603 - 608. doi:10.1016/j.jmb.2006.10.093
    • Hutchinson WL, Coll AP, Gallimore JR, Tennent GA, Pepys MB (2007). Is leptin an important physiological regulator of CRP?. Nat Med, 13(1), 17 - 18. doi:10.1038/nm0107-17
    • Hakobyan S, Harris CL, van den Berg C, Pepys MB, Morgan BP (2007). Binding of factor H to C-reactive protein occurs only when the latter has undergone non-physiologic denaturation. doi:10.1016/j.molimm.2007.06.194
    • Tennent GA, Head MW, Bishop M, Hawkins PN, Will RG, Knight R, Peden AH, McCardle LM, Ironside JW, Pepys MB (2007). Disease-associated prion protein is not detectable in human systemic amyloid deposits. J Pathol, 213(4), 376 - 383.
    • Tennent GA, Brennan SO, Stangou AJ, O Grady J, Hawkins PN, Pepys MB (2007). Human plasma fibrinogen is synthesized in the liver. Blood, 109(5), 1971 - 1974. doi:10.1182/blood-2006-08-040956
    • Pepys MB, Tennent GA, Denton CP (2007). Serum amyloid P and fibrosis in systemic sclerosis: comment on the article by Tennent et al - Reply. Arthritis Rheum, 56(12), 4229 - 4230. doi:10.1002/art.23150
    • Pepys MB (2007). Science and serendipity. Clin Med, 7(6), 562 - 578.
    • Tennent GA, Dziadzio M, Triantafillidou E, Davies P, Gallimore JR, Denton CP, Pepys MB (2007). Normal circulating serum amyloid P component concentration in systemic sclerosis. Arthritis Rheum, 56(6), 2013 - 2017. doi:10.1002/art.22694

    2006

    • Gillmore JD, Offer M, Lachmann HJ, Goodman HJ, Tennent GA, Gallimore JR, Pepys MB, Hawkins PN (2006). A pilot study of the tolerability, safety and efficacy of CPHPC in patients with systemic amyloidosis.
    • Gillmore JD, Stangou AJ, Lachmann HJ, Goodman HJ, Wechalekar AD, Acheson J, Tennent GA, Bybee A, Gilbertson J, Rowczenio D, O'Grady J, Heaton ND, Pepys MB, Hawkins PN (2006). Organ transplantation in hereditary apolipoprotein AI amyloidosis. Am J Transplant, 6(10), 2342 - 2347. doi:10.1111/j.1600-6143.2006.01507.x
    • Pepys M (2006). Amyloidosis. Annu Rev Med, 57, 223 - 241.
    • Gillmore JD, Goodman HJ, Lachmann HJ, Offer M, Wechalekar AD, Joshi J, Pepys MB, Hawkins PN (2006). Sequential heart and autologous stem cell transplantation for systemic AL amyloidosis. Blood, 107(3), 1227 - 1229. doi:10.1182/blood-2005-08-3253
    • Armstrong GD, Mulvey GL, Marcato P, Griener TP, Kahan MC, Tennent GA, Sabin CA, Chart H, Pepys MB (2006). Human serum amyloid P component protects against Escherichia coli O157:H7 Shiga toxin 2 in vivo: therapeutic implications for hemolytic-uremic syndrome. J Infect Dis, 193(8), 1120 - 1124.
    • Lowe GDO, Pepys MB (2006). C-reactive protein and cardiovascular disease: weighing the evidence. Curr Atheroscler Rep, 8(5), 421 - 428.
    • Pepys MB, Hirschfield GM, Tennent GA, Gallimore JR, Kahan MC, Bellotti V, Hawkins PN, Myers RM, Smith MD, Polara A, Cobb AJ, Ley SV, Aquilina JA, Robinson CV, Sharif I, Gray GA, Sabin CA, Jenvey MC, Kolstoe SE, Thompson D, Wood SP (2006). Targeting C-reactive protein for the treatment of cardiovascular disease. Nature, 440(7088), 1217 - 1221. doi:10.1038/nature04672

    2005

    • Clapp BR, Hirschfield GM, Storry C, Gallimore JR, Stidwill RP, Singer M, Deanfield JE, MacAllister RJ, Pepys MB, Vallance P, Hingorani AD (2005). Inflammation and endothelial function: direct vascular effects of human C-reactive protein on nitric oxide bioavailability. Circulation, 111(12), 1530 - 1536. doi:10.1161/01.CIR.0000159336.31613.31
    • Pepys M (2005). CRP or not CRP? That is the question. Arterioscler Thromb Vasc Biol, 25(6), 1091 - 1094.
    • Hirschfield GM, Gallimore JR, Kahan MC, Hutchinson WL, Sabin CA, Benson GM, Dhillon AP, Tennent GA, Pepys MB (2005). Transgenic human C-reactive protein is not proatherogenic in apolipoprotein E-deficient mice. Proc Natl Acad Sci U S A, 102(23), 8309 - 8314. doi:10.1073/pnas.0503202102
    • Pepys MB (2005). Avoiding the effect of linked genes is crucial to elucidate the role of Apcs in autoimmunity - Reply. Nat Med, 11(1), 12 - 13. doi:10.1038/nm0105-12
    • Pepys MB, Hawkins PN, Kahan MC, Tennent GA, Gallimore JR, Graham D, Sabin CA, Zychlinsky A, de Diego J (2005). Proinflammatory effects of bacterial recombinant human C-reactive protein are caused by contamination with bacterial products, not by C-reactive protein itself. Circ Res, 97(11), e97 - 103.
    • Noursadeghi M, Pepys MB, Gallimore R, Cohen J (2005). Relationship of granulocyte colony stimulating factor with other acute phase reactants in man. Clin Exp Immunol, 140(1), 97 - 100.

    2004

    • MacGregor AJ, Gallimore JR, Spector TD, Pepys MB (2004). Genetic effects on baseline values of C-reactive protein and serum amyloid A protein: a comparison of monozygotic and dizygotic twins. Clin Chem, 50(1), 130 - 134.
    • Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GDO, Pepys MB, Gudnason V (2004). C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med, 350(14), 1387 - 1397.
    • Gillmore JD, Hutchinson WL, Herbert J, Bybee A, Mitchell DA, Hasserjian RP, Yamamura K, Suzuki M, Sabin CA, Pepys MB (2004). Autoimmunity and glomerulonephritis in mice with targeted deletion of the serum amyloid P component gene: SAP deficiency or strain combination?. Immunology, 112(2), 255 - 264.
    • Greenfield JR, Samaras K, Jenkins AB, Kelly PJ, Spector TD, Gallimore JR, Pepys MB, Campbell LV (2004). Obesity is an important determinant of baseline serum C-reactive protein concentration in monozygotic twins, independent of genetic influences. Circulation, 109(24), 3022 - 3028.
    • Hutchinson WL, Herbert J, Botto M, Pepys MB (2004). Classical and alternative pathway complement activation are not required for reactive systemic AA amyloid deposition in mice. Immunology, 112(2), 250 - 254.
    • Gomma AH, Hirschfield GM, Gallimore JR, Lowe GD, Pepys MB, Fox KM (2004). Preprocedural inflammatory markers do not predict restenosis after successful coronary stenting. Am Heart J, 147(6), 1071 - 1077.
    • Gill R, Kemp JA, Sabin C, Pepys MB (2004). Human C-reactive protein increases cerebral infarct size after middle cerebral artery occlusion in adult rats. J Cereb Blood Flow Metab, 24(11), 1214 - 1218.
    • Danesh J, Pepys M, Gudnason V (2004). C-reactive protein and coronary heart disease - Reply. N Engl J Med, 351(3), 297 - 298.

    2003

    • Pepys MB, Hirschfield GM (2003). C-reactive protein: a critical update. J Clin Invest, 111(12), 1805 - 1812. doi:10.1172/JCI200318921
    • Clapp B, Hirschfield G, MacAllister R, Gallimore R, Vallance P, Pepys M, Hingorani A (2003). C-reactive protein alters vascular reactivity by increasing nitric oxide production.
    • Pepys MB (2003). Dame Sheila Patricia Violet Sherlock. Biogr Mem Fellows R Soc, 49, 475 - 493.
    • Pepys MB, Bybee A, Booth DR, Bishop MT, Will RG, Little A-M, Prokupek B, Madrigal JA (2003). MHC typing in variant Creutzfeldt-Jakob disease. Lancet, 361(9356), 487 - 489. doi:10.1016/S0140-6736(03)12455-5
    • Koenig W, Sund M, Frohlich M, Lowel H, Hutchinson WL, Pepys MB (2003). Refinement of the association of serum C-reactive protein concentration and coronary heart disease risk by correction for within-subject variation over time: the MONICA Augsburg studies, 1984 and 1987. Am J Epidemiol, 158(4), 357 - 364. doi:10.1093/aje/kwg135
    • Gillmore JD, Hutchinson WL, Mitchell DA, Herbert J, Botto M, Walport MJ, Pepys MB (2003). Studies of serum amyloid P component (SAP) and antinuclear autoimmunity.
    • Lachmann HJ, Gallimore R, Gillmore JD, Carr-Smith HD, Bradwell AR, Pepys MB, Hawkins PN (2003). Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol, 122(1), 78 - 84. doi:10.1046/j.1365-2141.2003.04433.x
    • Hirschfield GM, Gallimore R, Gilbertson JA, Benson M, Pepys MB (2003). Systemic inflammation and atherogenesis in apoE knockout mice expressing Transgenic human C-reactive protein.
    • Gomma A, Hirschfield G, Gallimore J, Lowe G, Pepys M, Fox K (2003). Systemic markers of inflammation do not predict coronary in-stent restenosis in stable angina patients treated with HMG CoA reductase inhibitors.
    • Khuseyinova N, Imhof A, Trischler G, Rothenbacher D, Hutchinson WL, Pepys MB, Koenig W (2003). Determination of C-reactive protein: comparison of three high-sensitivity immunoassays. Clin Chem, 49(10), 1691 - 1695.
    • Hirschfield GM, Herbert J, Kahan MC, Pepys MB (2003). Human C-reactive protein does not protect against acute lipopolysaccharide challenge in mice. J Immunol, 171(11), 6046 - 6051.
    • Fröhlich M, Mühlberger N, Hanke H, Imhof A, Döring A, Pepys MB, Koenig W (2003). Markers of inflammation in women on different hormone replacement therapies. Ann Med, 35(5), 353 - 361.
    • Hirschfield GM, Pepys MB (2003). C-reactive protein and cardiovascular disease: new insights from an old molecule. QJM, 96(11), 793 - 807.

    2002

    • Lachmann HJ, Gilbertson JA, Gillmore JD, Hawkins PN, Pepys MB (2002). Unicentric Castleman's disease complicated by systemic AA amyloidosis: a curable disease. QJM, 95(4), 211 - 218.
    • Pepys MB, Herbert J, Hutchinson WL, Tennent GA, Lachmann HJ, Gallimore JR, Lovat LB, Bartfai T, Alanine A, Hertel C, Hoffmann T, Jakob-Roetne R, Norcross RD, Kemp JA, Yamamura K, Suzuki M, Taylor GW, Murray S, Thompson D, Purvis A, Kolstoe S, Wood SP, Hawkins PN (2002). Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature, 417(6886), 254 - 259. doi:10.1038/417254a
    • Lachmann HJ, Booth DR, Booth SE, Bybee A, Gilbertson JA, Gillmore JD, Pepys MB, Hawkins PN (2002). Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med, 346(23), 1786 - 1791. doi:10.1056/NEJMoa013354
    • Hawkins PN, Lachmann HJ, Pepys MB (2002). Hereditary amyloidosis - Reply. N Engl J Med, 347(15), 1207 - .
    • Pepys M (2002). Treating amyloid in the periphery and the brain.
    • Frohlich M, Sund M, Lowel H, Imhof A, Hoffmeister A, Pepys MB, Koenig W (2002). Association of smoking with markers of systemic inflammation: results of a population-based study.
    • Thompson D, Pepys MB, Tickle I, Wood S (2002). The structures of crystalline complexes of human serum amyloid P component with its carbohydrate ligand, the cyclic pyruvate acetal of galactose. J Mol Biol, 320(5), 1081 - 1086.
    • Koenig W, Pepys MB (2002). C-reactive protein risk prediction: low specificity, high sensitivity. Ann Intern Med, 136(7), 550 - 552.
    • Noursadeghi M, Bickerstaff MCM, Herbert J, Moyes D, Cohen J, Pepys MB (2002). Production of granulocyte colony-stimulating factor in the nonspecific acute phase response enhances host resistance to bacterial infection. J Immunol, 169(2), 913 - 919.
    • Lachmann HJ, Gillmore JD, Pepys MB, Hawkins PN (2002). Outcome in systemic AL amyloidosis following stem cell transplantation or infusional chemotherapy.
    • Fröhlich M, Sund M, Thorand B, Hutchinson WL, Pepys MB, Koenig W (2002). Lack of seasonal variation in C-reactive protein. Clin Chem, 48(3), 575 - 577.
    • Herbert J, Hutchinson WL, Carr J, Ives J, Jakob-Roetne R, Yamamura K, Suzuki M, Pepys MB (2002). Influenza virus infection is not affected by serum amyloid P component. Mol Med, 8(1), 9 - 15.

    2001

    • Peters A, Fröhlich M, Döring A, Immervoll T, Wichmann H-E, Hutchinson WL, Pepys MB, Koenig W (2001). Particulate air pollution is associated with an acute phase response in men; results from the MONICA-Augsburg Study. Eur Heart J, 22(14), 1198 - 1204.
    • Pepys MB, Hirschfield GM (2001). C-reactive protein and atherothrombosis. Ital Heart J, 2(3), 196 - 199.
    • Imhof A, Froehlich M, Brenner H, Boeing H, Pepys MB, Koenig W (2001). Effect of alcohol consumption on systemic markers of inflammation. Lancet, 357(9258), 763 - 767.
    • Gillmore JD, Lovat LB, Persey MR, Pepys MB, Hawkins PN (2001). Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein. Lancet, 358(9275), 24 - 29. doi:10.1016/S0140-6736(00)05252-1
    • Jiménez JL, Tennent G, Pepys M, Saibil HR (2001). Structural diversity of ex vivo amyloid fibrils studied by cryo-electron microscopy. J Mol Biol, 311(2), 241 - 247.
    • Chambers JC, Eda S, Bassett P, Karim Y, Thompson SG, Gallimore JR, Pepys MB, Kooner JS (2001). C-reactive protein, insulin resistance, central obesity, and coronary heart disease risk in Indian Asians from the United Kingdom compared with European whites. Circulation, 104(2), 145 - 150.
    • Pepys MB, Berger A (2001). The renaissance of C reactive protein. BMJ, 322(7277), 4 - 5.
    • Mabbott NA, Bruce ME, Botto M, Walport MJ, Pepys MB (2001). Temporary depletion of complement component C3 or genetic deficiency of C1q significantly delays onset of scrapie. Nat Med, 7(4), 485 - 487. doi:10.1038/86562
    • Dobson CM, Weissmann C, Pepys MB, Karplus M (2001). Prions and the lymphoreticular system - Discussion. Philos Trans R Soc Lond B Biol Sci, 356(1406), 184 - .
    • Pepys MB, Caughey B, Kelly JW, Ellis RJ, Collinge J, Perutz MF, Masel J (2001). Prion protein interconversions - Discussion. Philos Trans R Soc London B Biol Sci, 356(1406), 200 - 202.
    • Pepys MB (2001). Serum amyloid P component: normal functions and role in pathogenesis, diagnosis and treatment of amyloidosis.
    • Pepys MB (2001). Pathogenesis, diagnosis and treatment of systemic amyloidosis. Philos Trans R Soc Lond B Biol Sci, 356(1406), 203 - 210.
    • Pepys MB, Hirschfield GM (2001). C-reactive protein and its role in the pathogenesis of myocardial infarction. Ital Heart J, 2(11), 804 - 806.
    • Booth DR, Bellotti V, Mangione P, Booth S, Sunde M, Serpell LC, Robinson CV, Pepys MB, Hawkins PN (2001). Is lysozyme variant Thr70Asn amyloidogenic?.
    • Peto H, Lindquist S, Dobson CM, Perutz MF, Pepys M, Goldberg ME (2001). Investigating protein conformation-based inheritance and disease in yeast - Discussion. Philos Trans R Soc London B Biol Sci, 356(1406), 176 - .
    • Hutchinson WL, Herbert J, Botto M, Walport MJ, Pepys MB (2001). AA amyloid deposition is complement independent.

    2000

    • Fröhlich M, Imhof A, Berg G, Hutchinson WL, Pepys MB, Boeing H, Muche R, Brenner H, Koenig W (2000). Association between C-reactive protein and features of the metabolic syndrome: a population-based study. Diabetes Care, 23(12), 1835 - 1839.
    • Gillmore JD, Booth DR, Rela M, Heaton ND, Rahman V, Stangou AJ, Pepys MB, Hawkins PN (2000). Curative hepatorenal transplantation in systemic amyloidosis caused by the Glu526Val fibrinogen α-chain variant in an English family. QJM, 93(5), 269 - 275.
    • Hutchinson WL, Hohenester E, Pepys MB (2000). Human serum amyloid P component is a single uncomplexed pentamer in whole serum. Mol Med, 6(6), 482 - 493.
    • Booth DR, Gillmore JD, Lachmann HJ, Booth SE, Bybee A, Soytürk M, Akar S, Pepys MB, Tunca M, Hawkins PN (2000). The genetic basis of autosomal dominant familial Mediterranean fever. QJM, 93(4), 217 - 221.
    • Coker AR, Purvis A, Baker D, Pepys MB, Wood SP (2000). Molecular chaperone properties of serum amyloid P component. FEBS Lett, 473(2), 199 - 202.
    • Hutchinson WL, Koenig W, Fröhlich M, Sund M, Lowe GDO, Pepys MB (2000). Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population. Clin Chem, 46(7), 934 - 938.
    • Serpell LC, Sunde M, Benson MD, Tennent GA, Pepys MB, Fraser PE (2000). The protofilament substructure of amyloid fibrils. J Mol Biol, 300(5), 1033 - 1039.
    • Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Gallimore JR, Pepys MB (2000). Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ, 321(7255), 199 - 204.
    • Danesh J, Pepys MB (2000). C-reactive protein in healthy and in sick populations. Eur Heart J, 21(19), 1564 - 1565.
    • Noursadeghi M, Bickerstaff MCM, Gallimore JR, Herbert J, Cohen J, Pepys MB (2000). Role of serum amyloid P component in bacterial infection: protection of the host or protection of the pathogen. Proc Natl Acad Sci U S A, 97(26), 14584 - 14589.
    • Gillmore JD, Madhoo S, Pepys MB, Hawkins PN (2000). Renal transplantation for amyloid end-stage renal failure-insights from serial serum amyloid P component scintigraphy. Nucl Med Commun, 21(8), 735 - 740.
    • Booth DR, Pepys MB, Hawkins PN (2000). A novel variant of human lysozyme (T70N) is common in the normal population. Hum Mutat, 16(2), 180 - .

    1999

    • Koenig W, Sund M, Fröhlich M, Fischer H-G, Löwel H, Döring A, Hutchinson WL, Pepys MB (1999). C-reactive protein a sensitive marker of inflammation predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study 1984-92. Circulation, 99(2), 237 - 242.
    • Griselli M, Herbert J, Hutchinson WL, Taylor KM, Sohail M, Krausz T, Pepys MB (1999). C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med, 190(12), 1733 - 1739.
    • Gillmore JD, Booth DR, Pepys MB, Hawkins PN (1999). Hereditary cardiac amyloidosis associated with the transthyretin Ile122 mutation in a white man. Heart, 82(3), e2 - .
    • Gillmore JD, Booth DR, Madhoo S, Pepys MB, Hawkins PN (1999). Hereditary renal amyloidosis associated with variant lysozyme in a large English family. Nephrol Dial Transplant, 14(11), 2639 - 2644.
    • Bickerstaff MCM, Botto M, Hutchinson WL, Herbert J, Tennent GA, Bybee A, Mitchell DA, Cook HT, Butler PJG, Walport MJ (1999). Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat Med, 5(6), 694 - 697.
    • Tunca M, Kirkali G, Soytürk M, Akar S, Pepys MB, Hawkins PN (1999). Acute phase response and evolution of familial Mediterranean fever. Lancet, 353(9162), 1415 - .
    • Brett M, Persey MR, Reilly MM, Revesz T, Booth DR, Booth SE, Hawkins PN, Pepys MB, Morgan-Hughes JA (1999). Transthyretin Leu12Pro is associated with systemic, neuropathic and leptomeningeal amyloidosis. Brain, 122(2), 183 - 190.
    • Liuzzo G, Biasucci LM, Gallimore JR, Caligiuri G, Buffon A, Rebuzzi AG, Pepys MB, Maseri A (1999). Enhanced inflammatory response in patients with preinfarction unstable angina. J Am Coll Cardiol, 34(6), 1696 - 1703.
    • Koenig W, Rothenbacher D, Hoffmeister A, Miller M, Bode G, Adler G, Hombach V, März W, Pepys MB, Brenner H (1999). Infection with Helicobacter pylori is not a major independent risk factor for stable coronary heart disease: lack of a role of cytotoxin-associated protein A-positive strains and absence of a systemic inflammatory response. Circulation, 100(23), 2326 - 2331.
    • Fröhlich M, Döring A, Imhof A, Hutchinson WL, Pepys MB, Koenig W (1999). Oral contraceptive use is associated with a systemic acute phase response. Fibrinolysis & Proteolysis, 13(6), 239 - 244.
    • Danesh J, Muir J, Wong Y-K, Ward M, Gallimore JR, Pepys MB (1999). Risk factors for coronary heart disease and acute-phase proteins. A population-based study. Eur Heart J, 20(13), 954 - 959.
    • Thompson D, Pepys MB, Wood SP (1999). The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure, 7(2), 169 - 177.
    • Tan SY, Baillod R, Brown E, Farrington K, Soper C, Percy M, Clutterbuck E, Madhoo S, Pepys MB, Hawkins PN (1999). Clinical, radiological and serum amyloid P component scintigraphic features of β2-microglobulin amyloidosis associated with continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant, 14(6), 1467 - 1471.