Staff Profile

Dr Mark Little

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Personal Profile

Name: Mark Little Email: mark.little@ucl.ac.uk
Title: Dr Tel: 34903
Department: Div of Medicine Fax:
Position: Honorary Senior Lecturer Address: UCL Centre for Nephrology Royal Free, Rowland Hill St, London, NW3 2QG
Research Domain: Experimental Medicine, Infection Immunology & Inflammation Web Page:  

Profile

Research Description

My work aims to understand the immunopathogenic mechanisms underlying the development of glomerulonephritis, with a specific focus on ANCA-associated vasculitis. This is the commonest cause of rapidly progressive glomerulonephritis and is associated with autoimmunity directed against components of the neutrophil cytoplasm. The driving force behind this aim is the clinical need for biomarkers that accurately identify active vasculitis, and which predict those in whom immunosuppressive therapy can be safely withdrawn. The research strands that will help to address this aim include:

1.       In vitro characterisation of the functional effects of ANCA on neutrophils, with focus on use of systems biology approaches to define the intracellular perturbations induced by this autoantibody. These approaches include metabolomic and expression arrays.

2.       Development of improved in vivo systems to accurately model the pathological processes, thereby allowing generation and testing of novel biomarkers and therapies.

3.       Development of national and international clinical data sets linked to bio-repositories that will facilitate research on well phenotyped patient samples collected over time, and at different stages of the disease. Central to this effort is the UKVAS vasculitis registry.

4.       Improvement in imaging technologies to allow accurate non-invasive characterisation of the anatomical defects and degree of inflammation in upper airway granulomatosis with polyangiitis.

5.       Collaboration with the EUVAS international vasculitis clinical investigation group and the European Vasculitis Genetics Consortium with respect to clinical trials and large scale genetics studies.


Research Activities

ANCA-associated systemic vasculitis

Immunology of glomerulonephritis and transplantation

Education Description

UCL Collaborators

Dr Stephen Marks; Dr Shonit Punwani; Prof Christopher Denton; Dr Paul Brogan; Prof Susan Lightman; Dr Alan Salama

External Collaborators

Dr Mike Robson; Prof Lorarine Harper

Publications

    2013

    • Pepper RJ, Chanouzas D, Tarzi R, Little M, Caisian A, Walsh M, Pusey CD, Harper L, Salama AD, EUVAS Investigators (2013). Intravenous Cyclophosphamide and Plasmapheresis in Dialysis-Dependent ANCA-Associated Vasculitis. Clinical Journal of the American Society of Nephrology, 8, - .
    • Basu N, McClean A, Harper L, Amft EN, Dhaun N, Luqmani RA, Little MA, Jayne DR, Flossmann O, McLaren J, Kumar V, Erwig LP, Reid DM, Jones GT, Macfarlane GJ (2013). The characterisation and determinants of quality of life in ANCA associated vasculitis.. Ann Rheum Dis, , - . doi:10.1136/annrheumdis-2012-202750

    2012

    • Hong Y, Eleftheriou D, Hussain AA, Price-Kuehne FE, Savage CO, Jayne D, Little MA, Salama AD, Klein NJ, Brogan PA (2012). Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.. J Am Soc Nephrol, 23(1), 49 - 62. doi:10.1681/ASN.2011030298
    • Salama AD, Little MA (2012). Animal models of antineutrophil cytoplasm antibody-associated vasculitis.. Curr Opin Rheumatol, 24(1), 1 - 7. doi:10.1097/BOR.0b013e32834d2d52
    • Kiprianos AP, Morgan MD, Little MA, Harper L, Bacon PA, Young SP (2012). Elevated active secretory sphingomyelinase in antineutrophil cytoplasmic antibody-associated primary systemic vasculitis.. Ann Rheum Dis, 71(6), 1100 - 1102. doi:10.1136/annrheumdis-2011-200445
    • Little MA, Al-Ani B, Ren S, Al-Nuaimi H, Leite M, Alpers CE, Savage CO, Duffield JS (2012). Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system.. PLoS One, 7(1), e28626 - . doi:10.1371/journal.pone.0028626
    • Sharma H, Keshavan A, Little MA, Cross J, Lipman MC, Talukdar S, Hopkins S (2012). Fortuitous vasculitis.. Ren Fail, 34(3), 378 - 382. doi:10.3109/0886022X.2011.647337
    • Lyons PA, Rayner TF, Trivedi S, Holle JU, Watts RA, Jayne DR, Baslund B, Brenchley P, Bruchfeld A, Chaudhry AN, Cohen Tervaert JW, Deloukas P, Feighery C, Gross WL, Guillevin L, Gunnarsson I, Harper L, Hrušková Z, Little MA, Martorana D, Neumann T, Ohlsson S, Padmanabhan S, Pusey CD, Salama AD, Sanders JS, Savage CO, Segelmark M, Stegeman CA, Tesař V, Vaglio A, Wieczorek S, Wilde B, Zwerina J, Rees AJ, Clayton DG, Smith KG (2012). Genetically distinct subsets within ANCA-associated vasculitis.. N Engl J Med, 367(3), 214 - 223. doi:10.1056/NEJMoa1108735

    2011

    • Heeringa P, Little MA (2011). In vivo approaches to investigate ANCA-associated vasculitis: lessons and limitations.. Arthritis Res Ther, 13(1), 204 - . doi:10.1186/ar3236
    • Al-Ani B, Al Nuaimi H, Savage C (2011). The beneficial effects of statin therapy may not apply to all forms of crescentic glomerulonephritis.. Am J Pathol, 178(5), 2447 - . doi:10.1016/j.ajpath.2010.12.058
    • Goceroglu A, Berden AE, van Dijk MCRF, de Joode AAE, Peutz-Kootstra CJ, Christiaans MHL, Smedts FMM, Noorlander I, Goldschmeding R, van Zuilen A, Steenbergen EJ, Hilbrands LB, Reinders M, Harper L, Little MA, Hagen EC, Bruijn JA, Bajema IM (2011). Dutch Transplantation in Vasculitis Study (DUTRAVAS): a multi-centre study on the outcome of renal transplantation in ANCA-AAV patients.
    • Al-Ani B, Al Nuaimi H, Smith S, Young SP, Savage C, Little MA (2011). Remission, relapse and renal scarring in EAV.
    • Little MA, Al-Ani B, Ren SY, Al-Nuaimi H, Alpers CE, Savage C, Duffield JS (2011). Human anti-PR3 ANCA recapitulate systemic vasculitis in mice with a humanized immune system.
    • Kiprianos AP, Morgan MD, Little MA, Savage COS, Harper L, Bacon PA, Young SP (2011). Elevated active secretory acid sphingomyelinase activity in ANCA-AAV.
    • Moore J, He XA, Liu XA, Shabir S, Ball S, Cockwell P, Inston N, Little MA, Johnston A, Borrows R (2011). Mortality Prediction After Kidney Transplantation: Comparative Clinical Use of 7 Comorbidity Indices. EXP CLIN TRANSPLANT, 9(1), 32 - 41.
    • Mansur A, Little MA, Oh WC, Jacques S, Nightingale P, Howie AJ, Savage CO (2011). Immune profile and Epstein-Barr virus infection in acute interstitial nephritis: an immunohistochemical study in 78 patients.. Nephron Clin Pract, 119(4), c293 - c300. doi:10.1159/000329671
    • Moore J, He X, Shabir S, Hanvesakul R, Benavente D, Cockwell P, Little MA, Ball S, Inston N, Johnston A, Borrows R (2011). Development and evaluation of a composite risk score to predict kidney transplant failure.. Am J Kidney Dis, 57(5), 744 - 751. doi:10.1053/j.ajkd.2010.12.017
    • Suppiah R, Flossman O, Mukhtyar C, Alberici F, Baslund B, Brown D, Hasan N, Holle J, Hruskova Z, Jayne D, Judge A, Little MA, Merkel PA, Palmisano A, Seo P, Stegeman C, Tesar V, Vaglio A, Westman K, Luqmani R (2011). Measurement of damage in systemic vasculitis: a comparison of the Vasculitis Damage Index with the Combined Damage Assessment Index.. Ann Rheum Dis, 70(1), 80 - 85. doi:10.1136/ard.2009.122952
    • Suppiah R, Mukhtyar C, Flossmann O, Alberici F, Baslund B, Batra R, Brown D, Holle J, Hruskova Z, Jayne DR, Judge A, Little MA, Palmisano A, Stegeman C, Tesar V, Vaglio A, Westman K, Luqmani R (2011). A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis.. Rheumatology (Oxford), 50(5), 899 - 905. doi:10.1093/rheumatology/keq400

    2010

    • Basu N, Watts R, Bajema I, Baslund B, Bley T, Boers M, Brogan P, Calabrese L, Cid MC, Cohen-Tervaert JW, Flores-Suarez LF, Fujimoto S, de Groot K, Guillevin L, Hatemi G, Hauser T, Jayne D, Jennette C, Kallenberg CG, Kobayashi S, Little MA, Mahr A, McLaren J, Merkel PA, Ozen S, Puechal X, Rasmussen N, Salama A, Salvarani C, Savage C, Scott DG, Segelmark M, Specks U, Sunderköetter C, Suzuki K, Tesar V, Wiik A, Yazici H, Luqmani R (2010). EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis.. Ann Rheum Dis, 69(10), 1744 - 1750. doi:10.1136/ard.2009.119032
    • Little MA, Nightingale P, Verburgh CA, Hauser T, De Groot K, Savage C, Jayne D, Harper L, European Vasculitis Study (EUVAS) Group (2010). Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis.. Ann Rheum Dis, 69(6), 1036 - 1043. doi:10.1136/ard.2009.109389

    2009

    • Little M, Savage C, Harper L (2009). Systematic variation in pulsed cyclophosphamide dosing between systemic vasculitis and SLE: the middle-aged/moderate renal dysfunction bulge. APMIS, 117, 80 - 80.
    • Sangha G, Al-Ani B, Al-Nuaimi H, Mukherjee S, Salama A, Pusey C, Little M (2009). Absence of myeloperoxidase renal deposition in rat experimental autoimmune vasculitis.
    • Harper L, Williams J, De Jong AM, Al Nuaimi H, Pallan L, Sarween N, Jesky E, Holden N, Savage C, Little M (2009). Relative impact of ANCA source and neutrophil donor on the neutrophil response to ANCA stimulation. APMIS, 117, 123 - 123.
    • Kiprianos A, Church L, Ahmad S, Little M, Savage C, Bacon P, Young S (2009). Acid sphingomyelinase as a mediator of cardiovascular damage in vasculitis. APMIS, 117, 130 - 130.
    • Little MA, Smyth L, Salama AD, Mukherjee S, Smith J, Haskard D, Nourshargh S, Cook HT, Pusey CD (2009). Experimental autoimmune vasculitis: an animal model of anti-neutrophil cytoplasmic autoantibody-associated systemic vasculitis.. Am J Pathol, 174(4), 1212 - 1220. doi:10.2353/ajpath.2009.080458
    • Moore J, Middleton L, Cockwell P, Adu D, Ball S, Little MA, Ready A, Wheatley K, Borrows R (2009). Calcineurin inhibitor sparing with mycophenolate in kidney transplantation: a systematic review and meta-analysis. Transplantation, 87(4), 591 - 605.
    • Moore J, Ramakrishna S, Tan K, Cockwell P, Eardley K, Little MA, Rylance P, Shivakumar K, Suresh V, Tomlinson K, Ready A, Borrows R (2009). Identification of the optimal donor quality scoring system and measure of early renal function in kidney transplantation.. Transplantation, 87(4), 578 - 586. doi:10.1097/TP.0b013e3181949e71
    • He X, Moore J, Shabir S, Little MA, Cockwell P, Ball S, Liu X, Johnston A, Borrows R (2009). Comparison of the predictive performance of eGFR formulae for mortality and graft failure in renal transplant recipients.. Transplantation, 87(3), 384 - 392. doi:10.1097/TP.0b013e31819004a1
    • He X, Moore J, Liu X, Shabir S, Cockwell P, Little MA, Ball S, Inston N, Johnston A, Borrows R (2009). A Simple "Kidney Risk Score" (KRS) and "Mortality Risk Score" (MRS) for Renal Transplant Recipients..
    • Pankhurst T, Savage CO, Little MA (2009). Review article: Leukocyte-endothelial dysregulation in systemic small vessel vasculitis.. Nephrology (Carlton), 14(1), 3 - 10. doi:10.1111/j.1440-1797.2008.01076.x
    • Kai A, Espinel-Costoso L, Trivedi S, Casal A, Morgan M, Levy J, Little MA, Pusey C, Jayne D, Salama AD (2009). Outcomes of a UK cohort of AAV patients treated with TNF blockade.
    • Moore J, Liu X, He X, Shabir S, Ball S, Cockwell P, Inston N, Little MA, Borrows R, Johnston A (2009). Impact of Comorbidity on Mortality Following Renal Transplantation: Comparative Clinical Utility of Seven Scoring Systems..
    • Little MA, Hassan B, Jacques S, Game D, Salisbury E, Courtney AE, Brown C, Salama AD, Harper L (2009). Renal transplantation in systemic vasculitis: when is it safe?. Nephrol Dial Transplant, 24(10), 3219 - 3225. doi:10.1093/ndt/gfp347

    2008

    • Nathani N, Little MA, Kunst H, Wilson D, Thickett DR (2008). Churg-Strauss syndrome and leukotriene antagonist use: a respiratory perspective.. Thorax, 63(10), 883 - 888. doi:10.1136/thx.2007.093955
    • Moore J, He X, Cockwell P, Little MA, Johnston A, Borrows R (2008). The impact of hemoglobin levels on patient and graft survival in renal transplant recipients.. Transplantation, 86(4), 564 - 570. doi:10.1097/TP.0b013e318181e276
    • Wong CF, Little MA, Vinjamuri S, Hammad A, Harper JM (2008). Technetium myocardial perfusion scanning in prerenal transplant evaluation in the United kingdom.. Transplant Proc, 40(5), 1324 - 1328. doi:10.1016/j.transproceed.2008.03.143
    • Little MA, Savage CO (2008). The role of the endothelium in systemic small vessel vasculitis.. Clin Exp Rheumatol, 26(3 Suppl 49), S135 - S140.
    • Winstanley V, Little MA, Wadsworth C, Cohen P, Martin NM (2008). The McKittrick-Wheelock syndrome: a case of acute renal failure due to neoplastic cholera.. Ren Fail, 30(4), 469 - 473. doi:10.1080/08860220801964277

    2007

    • Little MA, Hussein T, Lambert M, Dickson SJ (2007). Percutaneous venepuncture practice in a large urban teaching hospital. CLIN MED, 7(3), 243 - 249.
    • Malik AR, Little MA, Henriksson M, Tam FW, Brown EA (2007). Peritonitis, peritoneal inflammation and membrane permeability: a longitudinal study of dialysate and serum MCP-1 in stable patients on peritoneal dialysis.. J Nephrol, 20(3), 340 - 349.

    2006

    • Ambrose L, Smith L, Little M, Dupont P, Williams G, Warrens A (2006). Neutrophils as antigen-presenting cells in transplantation: Bridging innate and adaptive immunity.
    • Little MA (2006). Current and future therapy of small vessel vasculitis of the kidney.. Minerva Urol Nefrol, 58(1), 39 - 52.
    • McMahon G, Abraham K, Little M, Fitzgerald R, Kennelly M, Walshe JJ (2006). A longitudinal study of catecholamine production in pregnancy.
    • Little MA, Dupont P, Campbell E, Dorman A, Walshe JJ (2006). Response to 'Differences between type I and II membranoproliferative glomerulonephritis'. KIDNEY INT, 70(8), 1527 - 1527. doi:10.1038/sj.ki.5001769
    • Little MA, Dupont P, Campbell E, Dorman A, Walshe JJ (2006). Severity of primary MPGN, rather than MPGN type, determines renal survival and post-transplantation recurrence risk.. Kidney Int, 69(3), 504 - 511. doi:10.1038/sj.ki.5000084
    • Little MA, Bhangal G, Smyth CL, Nakada MT, Cook HT, Nourshargh S, Pusey CD (2006). Therapeutic effect of anti-TNF-alpha antibodies in an experimental model of anti-neutrophil cytoplasm antibody-associated systemic vasculitis.. J Am Soc Nephrol, 17(1), 160 - 169. doi:10.1681/ASN.2005060616

    2005

    • Little MA, Pusey CD, Nourshargh S (2005). Intravital microscopy in the study of ANCA-associated systemic vasculitis.. Clin Nephrol, 64(6), 465 - 470.
    • Ambrose LR, Little MA, Nourshargh S, Pusey CD (2005). Anti-proteinase 3 antibody binding to neutrophils as demonstrated by confocal microscopy.. Kidney Int, 68(6), 2912 - 2913. doi:10.1111/j.1523-1755.2005.00583_10.x
    • Ambrose LR, Smith LM, Little MA, Dupont PJ, Herbert PE, Williams G, Lombardi G, Warrens AN (2005). PMNs as APCs in transplantation: bridging innate and adaptive immunity. IMMUNOLOGY, 116, 48 - 48.
    • Little MA, Smyth CL, Yadav R, Ambrose L, Cook HT, Nourshargh S, Pusey CD (2005). Antineutrophil cytoplasm antibodies directed against myeloperoxidase augment leukocyte-microvascular interactions in vivo. Blood, 106(6), 2050 - 2058.
    • Little MA, Pusey CD (2005). Glomerulonephritis due to antineutrophil cytoplasm antibody-associated vasculitis: an update on approaches to management.. Nephrology (Carlton), 10(4), 368 - 376. doi:10.1111/j.1440-1797.2005.00434.x
    • Little MA, Cafferky M, Menon S, Farrington K (2005). Dialysis amyloid: the bottom line.. Nephrol Dial Transplant, 20(2), 462 - 463. doi:10.1093/ndt/gfh450

    2004

    • Gandhi S, Little MA, Farrington K (2004). Waldenstrom's macroglobulinemia presenting as Goodpasture's syndrome.. Ren Fail, 26(5), 591 - 596.
    • Little MA, Pusey CD (2004). Rapidly progressive glomerulonephritis: current and evolving treatment strategies.. J Nephrol, 17 Suppl 8, S10 - S19.
    • Little MA, Nazar L, Farrington K (2004). Polymyalgia rheumatica preceding small-vessel vasculitis: changed spots or misdiagnosis?. QJM, 97(5), 289 - 292.
    • Little MA, Nazar L, Farrington K (2004). Outcome in glomerulonephritis due to systemic small vessel vasculitis: effect of functional status and non-vasculitic co-morbidity.. Nephrol Dial Transplant, 19(2), 356 - 364.

    2003

    • Little MA, Smyth L, Buchatska O, Bhangal G, Wang S, Nourshargh S, Pusey CD (2003). Comparison of the binding characteristics of ANCA from vasculitic patients with ANCA from a novel rat model of systemic vasculitis..
    • Little MA, Nazar L, Farrington K (2003). Outcome in glomerulonephritis due to ANCA-associated small vessel vasculitis effect of functional status and non-vasculitic co-morbidity..
    • Little MA, O'Brien E, Owens P, Holian J, Kenny S, Mee F, Walshe JJ (2003). A longitudinal study of the yield and clinical utility of a specifically designed secondary hypertension investigation protocol.. Ren Fail, 25(5), 709 - 717.
    • Williams A, Little M, Gibbs J, Warwicker P, Farrington K (2003). Spinal cord infarction following central-line insertion.. Ren Fail, 25(2), 327 - 329.

    2002

    • Donne RL, Abbs I, Barany P, Elinder CG, Little M, Conlon P, Goodship TH (2002). Recurrence of hemolytic uremic syndrome after live related renal transplantation associated with subsequent de novo disease in the donor.. Am J Kidney Dis, 40(6), E22 - . doi:10.1053/ajkd.2002.36938
    • McEntagart M, Parsons G, Buj-Bello A, Biancalana V, Fenton I, Little M, Krawczak M, Thomas N, Herman G, Clarke A, Wallgren-Pettersson C (2002). Genotype-phenotype correlations in X-linked myotubular myopathy.. Neuromuscul Disord, 12(10), 939 - 946.
    • Little MA, Walshe JJ (2002). A longitudinal study of the repeated use of alteplase as therapy for tunneled hemodialysis catheter dysfunction.. Am J Kidney Dis, 39(1), 86 - 91. doi:10.1053/ajkd.2002.29885

    2001

    • Little MA, O'Riordan A, Lucey B, Farrell M, Lee M, Conlon PJ, Walshe JJ (2001). A prospective study of complications associated with cuffed, tunnelled haemodialysis catheters.. Nephrol Dial Transplant, 16(11), 2194 - 2200.
    • Conlon PJ, Little MA, Pieper K, Mark DB (2001). Severity of renal vascular disease predicts mortality in patients undergoing coronary angiography.. Kidney Int, 60(4), 1490 - 1497. doi:10.1046/j.1523-1755.2001.00953.x

    2000

    • Little MA, Conlon PJ, Walshe JJ (2000). Access recirculation in temporary hemodialysis catheters as measured by the saline dilution technique.. Am J Kidney Dis, 36(6), 1135 - 1139. doi:10.1053/ajkd.2000.19821
    • Abraham KA, Little MA, Casey R, Smyth E, Walshe JJ (2000). A novel presentation of cryptococcal infection in a renal allograft recipient.. Ir Med J, 93(3), 82 - 84.
    • Little MA, Stafford Johnson DB, O'Callaghan JP, Walshe JJ (2000). The diagnostic yield of intravenous urography.. Nephrol Dial Transplant, 15(2), 200 - 204.
    • Little MA, Abraham KA, Kavanagh J, Connolly G, Byrne P, Walshe JJ (2000). Pregnancy in Irish renal transplant recipients in the cyclosporine era.. Ir J Med Sci, 169(1), 19 - 21.
    • Little MA, Dorman A, Gill D, Walshe JJ (2000). Mesangioproliferative glomerulonephritis with IgM deposition: clinical characteristics and outcome.. Ren Fail, 22(4), 445 - 457.
    • Abraham KA, Little MA, Dorman AM, Walshe JJ (2000). Hemolytic-uremic syndrome in association with both cyclosporine and tacrolimus.. Transpl Int, 13(6), 443 - 447.