Critical Care Translational Biology

Research Interests

  • Sepsis is the most common critical illness syndrome that is responsible for 20% of all deaths around the world. Sepsis results from systemic inflammation after uncontrolled local infection, which can be caused by bacteria, viruses (ex: COVID-19), or fungus. Mechanisms of sepsis pathology remain obscure. As a consequence, specific therapies are lacking.

    An additional key target in sepsis is the endothelium, a network of cells that line blood vessels that orchestrate the recruitment of immune cells to the site of infection. The interplay between immune and endothelial activation in sepsis is poorly understood.

    Our laboratory studies early biological samples from patients admitted to the Intensive Care Unit to understand how heterogeneity in the immune response and endothelial injury relate to patient outcomes, including the risk of developing hospital-acquired infections, the severity of illness, response to therapies, cardiovascular complications, and cognitive function after hospital discharge.

  • 1. How is the immune system regulated in early sepsis?

    Excessive immune activation and immune suppression are both central to sepsis biology. One of the measures of a dysregulated immune response in sepsis is endotoxin tolerance, or the inability of immune cells to respond to secondary stimuli. The mechanisms of this refractory state, its duration, and its link to poor outcomes might determine which patients may benefit from immunomodulatory therapies to improve sepsis outcomes. We study patient immune responses to secondary stimuli using flow cytometry, ex vivo cellular assays, immunohistochemistry, and RNA sequencing.

  • 2. How does the endothelium respond to immune activation?

    When endothelial cells are in a pro-inflammatory milieu, their permeability increases and the expression of their surface proteins changes. These processes result in tissue edema, coagulation, and migration of immune cells. It is uncertain whether altering the expression of these and other proteins may repair the endothelium and improve clinical outcomes. To understand the interplay between immune and endothelial injury, we use electric cell-substrate impedance sensing (ECIS) to study human pulmonary microvascular endothelial cells permeability after exposure to human samples and compounds that modulate endothelial injury.

  • 3. What biologic treatable traits define early critical illness?

    The clinical definitions of critical illness syndromes (i.e.: sepsis, ARDS) are non-specific. Incorporating biology in their classification may improve their diagnosis, prognosis, and treatment options. Large and diverse patient cohorts are needed to perform “omics”-based analyses to account for the heterogeneity associated with critical illness. We biobank samples from patients with early critical illness and perform large-scale translational studies (transcriptomics, proteomics). This research will identify treatable biologic traits that can improve our understanding of critical illness syndromes and enable precision medicine therapies.

  • Publications

    Leligdowicz A. Are We Ready for Biomarker-Guided Immune Modulation in Critical Care? Crit Care Med 2023 Dec 1;51(12):1827-1829.

    Barber G, Tanic J, Leligdowicz A. Circulating protein and lipid markers of early sepsis diagnosis and prognosis: a scoping review. Curr Opin Lipidol 2023; 34: 70-81.

    Leligdowicz A, Kamm J, Kalantar K, Jauregui A, Vessel K, Caldera S, Serpa PH, Abbott J, Fang X, Tian X, Prakash A, Kangelaris KN, Liu KD, Calfee CS, Langelier C, Matthay MA. Functional Transcriptomic Studies of Immune Responses and Endotoxin Tolerance In early Human Sepsis. Shock 2022.

    Leligdowicz A, Harhay MO, Calfee CS. Immune modulation in critical illness: The Road Traveled and The Road Ahead. NEJM Evid 2022; 1 (11).

    Marshall JC, Leligdowicz A. Gaps and Opportunities in Sepsis Translational Research. eBioMedicine 2022.

    Maslove DM, Tang B, Shankar-Hari M, Lawler PR, Angus DC, Baillie JK, Baron RM, Bauer M, Buchman TG, Calfee CS, Dos Santos CC, Giamarellos-Bourboulis EJ, Gordon AC, Kellum JA, Knight JC, Leligdowicz A, McAuley DF, McLean AS, Menon DK, Meyer NJ, Moldawer LL, Reddy K, Reilly JP, Russell JA, Sevransky JE, Seymour CW, Shapiro NI, Singer M, Summers C, Sweeney TE, Thompson BT, van der Poll T, Venkatesh B, Walley KR, Walsh TS, Ware LB, Wong HR, Zador ZE, Marshall JC. Redefining critical illness. Nat Med 2022; 28: 1141-1148.

    Martin CM, Slessarev M, Campbell E, Basmaji J, Ball I, Fraser DD, Leligdowicz A, Mele T, Priestap F, Tschirhart BJ, Bentall T, Lu X, Feng Q. Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial. Crit Care Explor 2023; 5: e0986.

    Sinha P, Kerchberger VE, Willmore A, Chambers J, Zhuo H, Abbott J, Jones C, Wickersham N, Wu N, Neyton L, Langelier CR, Mick E, He J, Jauregui A, Churpek MM, Gomez AD, Hendrickson CM, Kangelaris KN, Sarma A, Leligdowicz A, Delucchi KL, Liu KD, Russell JA, Matthay MA, Walley KR, Ware LB, Calfee CS. Identifying molecular phenotypes in sepsis: an analysis of two prospective observational cohorts and secondary analysis of two randomised controlled trials. Lancet Respir Med 2023.

    Alipanah-Lechner N, Neyton L, Mick E, Willmore A, Leligdowicz A, Contrepois K, Jauregui A, Zhuo H, Hendrickson C, Gomez A, Sinha P, Kangelaris KN, Liu KD, Matthay MA, Rogers AJ, Calfee CS. Plasma metabolic profiling implicates dysregulated lipid metabolism and glycolytic shift in hyperinflammatory ARDS. Am J Physiol Lung Cell Mol Physiol 2023; 324: L297-L306.

    Rosenberger CM, Wick KD, Zhuo H, Wu N, Chen Y, Kapadia SB, Guimaraes A, Chang D, Choy DF, Chen H, Peck M, Sullivan KM, Ke S, Jauregui A, Leligdowicz A, Sinha P, Gomez AD, Kangelaris KN, Delucchi K, Liu KD, Calfee CS, Matthay MA, Hendrickson CM. Early plasma angiopoietin-2 is prognostic for ARDS and mortality among critically ill patients with sepsis. Crit Care. 2023 Jun 13;27(1):234.

    Weckman AM, McDonald CR, Ngai M, Richard-Greenblatt M, Leligdowicz A, Conroy AL, Kain KC, Namasopo S, Hawkes MT. Inflammatory profiles in febrile children with moderate and severe malnutrition presenting at-hospital in EBioMedicineUganda are associated with increased mortality. EBioMedicine 2023; 94: 104721.

    Van Singer M, Brahier T, Koch J, Hugli PO, Weckman AM, Zhong K, Kain TJ, Leligdowicz A, Bernasconi E, Ceschi A, Parolari S, Vuichard-Gysin D, Kain KC, Albrich WC, Boillat-Blanco N. Validation of sTREM-1 and IL-6 based algorithms for outcome prediction of COVID-19. BMC Infect Dis 2023; 23: 630.

    Van Nynatten LR, Slessarev M, Martin CM, Leligdowicz A, Miller MR, Patel MA, Daley M, Patterson EK, Cepinskas G, Fraser DD. Novel plasma protein biomarkers from critically ill sepsis patients. Clin Proteomics 2022; 19: 50.

    Wick KD, Leligdowicz A, Willmore A, Carrillo SA, Ghale R, Jauregui A, Chak SS, Nguyen V, Lee D, Jones C, Dewar R, Lane HC, Kangelaris KN, Hendrickson CM, Liu KD, Sinha P, Erle DJ, Langelier CR, Krummell MF, Woodruff PG, Calfee CS, Matthay MA, Consortium C. Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19. Crit Care 2022; 26: 278.

    Kalantar K, Neyton L, Abdelghany M, Mick E, Jauregui A, Caldera S, Hayakawa Serpa P, Ghale R, Albright J, Sarma A, Tsitsiklis A, Leligdowicz A, Christenson SA , Liu K, Kangelaris KN, Hendrickson C, Sinha P, Gomez A, Neff N, Pisco A, Doernberg SB, Derisi JL, Matthay MA, Calfee CS, Langelier CR. Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults. Nat Microbiol 2022; 7(11):1805-1816.

    Leligdowicz A, Conroy AL, Hawkes M, Richard-Greenblatt M, Zhong K, Opoka RO, Namasopo S, Bell D, Liles WC, da Costa BR, Juni P, Kain KC. Risk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test. Nat Commun 2021; 12: 6832.

    Sinha P, Delucchi KL, Chen Y, Zhuo H, Abbott J, Wang C, Wickersham N, McNeil JB, Jauregui A, Ke S, Vessel K, Gomez A, Hendrickson CM, Kangelaris KN, Sarma A, Leligdowicz A, Liu KD, Matthay MA, Ware LB, Calfee CS. Latent class analysis-derived subphenotypes are generalisable to observational cohorts of acute respiratory distress syndrome: a prospective study. Thorax 2022; 77: 13-21.

    Maddali MV, Churpek M, Pham T, Rezoagli E, Zhuo H, Zhao W, He J, Delucchi KL, Wang C, Wickersham N, McNeil JB, Jauregui A, Ke S, Vessel K, Gomez A, Hendrickson CM, Kangelaris KN, Sarma A, Leligdowicz A, Liu KD, Matthay MA, Ware LB, Laffey JG, Bellani G, Calfee CS, Sinha P, Investigators LS, the ETG. Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis. Lancet Respir Med 2022; 10: 367-377.

    Hawkes MT, Leligdowicz A, Batte A, Situma G, Zhong K, Namasopo S, Opoka RO, Kain KC, Conroy AL. Pathophysiology of Acute Kidney Injury in Malaria and Non-Malarial Febrile Illness: A Prospective Cohort Study. Pathogens 2022; 11.

    McDonald CR, Weckman AM, Richardson E, Hawkes MT, Leligdowicz A, Namasopo S, Opoka RO, Conroy AL, Kain KC. Sex as a determinant of disease severity and clinical outcome in febrile children under five presenting to a regional referral hospital in Uganda. PloS one 2022; 17: e0276234.

    Conroy AL, Hawkes MT, Leligdowicz A, Mufumba I, Starr MC, Zhong K, Namasopo S, John CC, Opoka RO, Kain KC. Blackwater fever and acute kidney injury in children hospitalized with an acute febrile illness: pathophysiology and prognostic significance. BMC Med 2022; 20: 221.

    Ozonoff A, Schaenman J, Jayavelu ND, Milliren CE, Calfee CS, Cairns CB, Kraft M, Baden LR, Shaw AC, Krammer F, van Bakel H, Esserman DA, Liu S, Sesma AF, Simon V, Hafler DA, Montgomery RR, Kleinstein SH, Levy O, Bime C, Haddad EK, Erle DJ, Pulendran B, Nadeau KC, Davis MM, Hough CL, Messer WB, Higuita NIA, Metcalf JP, Atkinson MA, Brakenridge SC, Corry D, Kheradmand F, Ehrlich LIR, Melamed E, McComsey GA, Sekaly R, Diray-Arce J, Peters B, Augustine AD, Reed EF, Altman MC, Becker PM, Rouphael N, members Isg. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study. EBioMedicine 2022; 83: 104208.

    Matthay ZA, Fields AT, Nunez-Garcia B, Park JJ, Jones C, Leligdowicz A, Hendrickson CM, Callcut RA, Matthay MA, Kornblith LZ. Importance of catecholamine signaling in the development of platelet exhaustion after traumatic injury. J Thromb Haemost 2022.

    Moazed F, Hendrickson C, Jauregui A, Gotts J, Conroy A, Delucchi K, Zhuo H, Arambulo M, Vessel K, Ke S, Deiss T, Ni A, Leligdowicz A, Abbott J, Cohen MJ, Sinha P, Gomez A, Kangelaris K, Kornblith L, Matthay M, Benowitz N, Liu K, Calfee CS. Cigarette Smoke Exposure and Acute Respiratory Distress Syndrome in Sepsis: Epidemiology, Clinical Features, and Biologic Markers. Am J Respir Crit Care Med 2022; 205: 927-935.

    Wick KD, Leligdowicz A, Zhuo H, Ware LB, Matthay MA. Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS. JCI Insight 2021; 6.

    Leligdowicz A, Matthay MA. Carbonic Anhydrase IX: Scaring Away the Grim Reaper in Acute Lung Injury? Am J Respir Cell Mol Biol 2021; 65: 573-575.

    Shah FA, Meyer NJ, Angus DC, Awdish R, Azoulay E, Calfee CS, Clermont G, Gordon AC, Kwizera A, Leligdowicz A, Marshall JC, Mikacenic C, Sinha P, Venkatesh B, Wong HR, Zampieri FG, Yende S. A Research Agenda for Precision Medicine in Sepsis and Acute Respiratory Distress Syndrome: An Official American Thoracic Society Research Statement. Am J Respir Crit Care Med 2021; 204: 891-901.

    Combes AJ, Courau T, Kuhn NF, Hu KH, Ray A, Chen WS, Chew NW, Cleary SJ, Kushnoor D, Reeder GC, Shen A, Tsui J, Hiam-Galvez KJ, Munoz-Sandoval P, Zhu WS, Lee DS, Sun Y, You R, Magnen M, Rodriguez L, Im KW, Serwas NK, Leligdowicz A, Zamecnik CR, Loudermilk RP, Wilson MR, Ye CJ, Fragiadakis GK, Looney MR, Chan V, Ward A, Carrillo S, Consortium UC, Matthay M, Erle DJ, Woodruff PG, Langelier C, Kangelaris K, Hendrickson CM, Calfee C, Rao AA, Krummel MF. Global absence and targeting of protective immune states in severe COVID-19. Nature 2021; 591: 124-130.

    Rogers AJ, Leligdowicz A, Contrepois K, Jauregui A, Vessel K, Deiss TJ, Belzer A, Liu T, Lippi M, Ke S, Ross E, Zhou H, Hendrickson C, Gomez A, Sinha P, Kangelaris KN, Liu KD, Calfee CS, Matthay MA. Plasma Metabolites in Early Sepsis Identify Distinct Clusters Defined by Plasma Lipids. Crit Care Explor 2021; 3: e0478.

    Tsitsiklis A, Zha BS, Byrne A, DeVoe C, Rackaityte E, Levan S, Sunshine S, Mick E, Ghale R, Love C, Tarashansky AJ, Pisco A, Albright J, Jauregui A, Sarma A, Neff N, Serpa PH, Deiss TJ, Kistler A, Carrillo S, Ansel KM, Leligdowicz A, Christenson S, Detweiler A, Jones NG, Wu B, Darmanis S, Lynch SV, DeRisi JL, Consortium C, Matthay MA, Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Erle DJ, Rosenberg O, Calfee CS, Langelier CR. Impaired immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia in COVID-19. medRxiv 2021. https://www.ncbi.nlm.nih.gov/pubmed/33791731

    Sarma A, Christenson SA, Byrne A, Mick E, Pisco AO, DeVoe C, Deiss T, Ghale R, Zha BS, Tsitsiklis A, Jauregui A, Moazed F, Detweiler AM, Spottiswoode N, Sinha P, Neff N, Tan M, Serpa PH, Willmore A, Ansel KM, Wilson JG, Leligdowicz A, Siegel ER, Sirota M, DeRisi JL, Matthay MA, Consortium C, Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Erle DJ, Calfee CS, Langelier CR. Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS. Nat Commun 2021; 12: 5152.

    Kangelaris KN, Clemens R, Fang X, Jauregui A, Liu T, Vessel K, Deiss T, Sinha P, Leligdowicz A, Liu KD, Zhuo H, Alder MN, Wong HR, Calfee CS, Lowell C, Matthay MA. A neutrophil subset defined by intracellular olfactomedin 4 is associated with mortality in sepsis. Am J Physiol Lung Cell Mol Physiol 2021; 320: L892-L902.

    Leligdowicz A, Ross JT, Nesseler N, Matthay MA. The endogenous capacity to produce proinflammatory mediators by the ex vivo human perfused lung. Intensive Care Med Exp 2020; 8: 56.

    Ross JT, Nesseler N, Leligdowicz A, Zemans RL, Mahida RY, Minus E, Langelier C, Gotts JE, Matthay MA. The ex vivo perfused human lung is resistant to injury by high-dose S. pneumoniae bacteremia. Am J Physiol Lung Cell Mol Physiol 2020; 319: L218-L227.

    Matthay MA, Leligdowicz A, Liu KD. Biological Mechanisms of COVID-19 Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2020; 202: 1489-1491.

    Kwong YD, Mehta KM, Miaskowski C, Zhuo H, Yee K, Jauregui A, Ke S, Deiss T, Abbott J, Kangelaris KN, Sinha P, Hendrickson C, Gomez A, Leligdowicz A, Matthay MA, Calfee CS, Liu KD. Using best subset regression to identify clinical characteristics and biomarkers associated with sepsis-associated acute kidney injury. Am J Physiol Renal Physiol 2020; 319: F979-F987.

    Leligdowicz A, Matthay MA. Heterogeneity in sepsis: new biological evidence with clinical applications. Crit Care 2019; 23: 80.

    Leligdowicz A, Matthay MA. AIMing Immunomodulation Therapy at Sepsis. Am J Respir Cell Mol Biol 2019; 60: 253-254.

    Leligdowicz A. The Challenge and the Promise of Identifying More Homogeneous Subgroups in Acute Respiratory Distress Syndrome. Crit Care Med 2019; 47: 1806-1808.

    Leligdowicz A, Richard-Greenblatt M, Wright J, Crowley VM, Kain KC. Endothelial Activation: The Ang/Tie Axis in Sepsis. Front Immunol 2018; 9: 838.

    Leligdowicz A, Chun LF, Jauregui A, Vessel K, Liu KD, Calfee CS, Matthay MA. Human pulmonary endothelial cell permeability after exposure to LPS-stimulated leukocyte supernatants derived from patients with early sepsis. Am J Physiol Lung Cell Mol Physiol 2018; 315: L638-L644.

    Rojek AM, Dunning J, Leligdowicz A, Castle L, Van Lieshout M, Carson G, Sahr F, Olliaro P, Horby PW. Regulatory and Operational Complexities of Conducting a Clinical Treatment Trial During an Ebola Virus Disease Epidemic. Clin Infect Dis 2018; 66: 1454-1457.

    McDonald CR, Weckman A, Richard-Greenblatt M, Leligdowicz A, Kain KC. Integrated fever management: disease severity markers to triage children with malaria and non-malarial febrile illness. Malar J 2018; 17: 353.

    Mandelzweig K, Leligdowicz A, Murthy S, Lalitha R, Fowler RA, Adhikari NKJ. Non-invasive ventilation in children and adults in low- and low-middle income countries: A systematic review and meta-analysis. J Crit Care 2018; 47: 310-319.

    de Silva TI, Leligdowicz A, Carlson J, Garcia-Knight M, Onyango C, Miller N, Yindom LM, Hue S, Jaye A, Dong T, Cotten M, Rowland-Jones SL. HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation. AIDS 2018; 32: 709-714.

    Bansal S, Nguyen JP, Leligdowicz A, Zhang Y, Kain KC, Ricciuto DR, Coburn B. Rectal and Naris Swabs: Practical and Informative Samples for Analyzing the Microbiota of Critically Ill Patients. mSphere 2018; 3.

    Leligdowicz A, Conroy AL, Hawkes M, Zhong K, Lebovic G, Matthay MA, Kain KC. Validation of two multiplex platforms to quantify circulating markers of inflammation and endothelial injury in severe infection. PloS one 2017; 12: e0175130.

    Leligdowicz A, Bhagwanjee S, Diaz JV, Xiong W, Marshall JC, Fowler RA, Adhikari NK, Acute Care for Africa R, Training G, the International Forum of Acute Care T. Development of an intensive care unit resource assessment survey for the care of critically ill patients in resource-limited settings. J Crit Care 2017; 38: 172-176.

    Leligdowicz A, Fischer WA, 2nd, Uyeki TM, Fletcher TE, Adhikari NK, Portella G, Lamontagne F, Clement C, Jacob ST, Rubinson L, Vanderschuren A, Hajek J, Murthy S, Ferri M, Crozier I, Ibrahima E, Lamah MC, Schieffelin JS, Brett-Major D, Bausch DG, Shindo N, Chan AK, O'Dempsey T, Mishra S, Jacobs M, Dickson S, Lyon GM, 3rd, Fowler RA. Ebola virus disease and critical illness. Crit Care 2016; 20: 217.

    Bartz RR, Gantner D, Gordon AC, Leligdowicz A, McNamee JJ, Murthy S, Nichol A, Webb S, International Forum for Acute Care T. Who Says There Is No "I" in Team? Achieving Individual Success in Collaborative Clinical Research in Critical Care. Am J Respir Crit Care Med 2016; 194: 911-912.

    Leligdowicz A, Fan E. Extracorporeal life support for severe acute respiratory distress syndrome. Curr Opin Crit Care 2015; 21: 13-19.

    Murthy S, Leligdowicz A, Adhikari NK. Intensive care unit capacity in low-income countries: a systematic review. PloS one 2015; 10: e0116949.

    Jallow S, Leligdowicz A, Kramer HB, Onyango C, Cotten M, Wright C, Whittle HC, McMichael A, Dong T, Kessler BM, Rowland-Jones SL. The presence of prolines in the flanking region of an immunodominant HIV-2 gag epitope influences the quality and quantity of the epitope generated. Eur J Immunol 2015; 45: 2232-2242.

    Leligdowicz A, Dodek PM, Norena M, Wong H, Kumar A, Kumar A, Co-operative Antimicrobial Therapy of Septic Shock Database Research G. Association between source of infection and hospital mortality in patients who have septic shock. Am J Respir Crit Care Med 2014; 189: 1204-1213.

    Reikie BA, Adams RCM, Leligdowicz A, Ho K, Naidoo S, Rusk CE, de Beer C, Preiser W, Cotton MF, Speert DP, Esser M, Kollmann TR. Altered innate immune development in HIV-exposed uninfected infants. J Acquir Immune Defic Syndr 2014; 66: 245-255.

    Goldenberg NM, Leligdowicz A, Slutsky AS, Friedrich JO, Lee WL. Is nosocomial infection really the major cause of death in sepsis? Crit Care 2014; 18: 540.

    de Silva TI, Peng Y, Leligdowicz A, Zaidi I, Li L, Griffin H, Blais ME, Vincent T, Saraiva M, Yindom LM, van Tienen C, Easterbrook P, Jaye A, Whittle H, Dong T, Rowland-Jones SL. Correlates of T-cell-mediated viral control and phenotype of CD8(+) T cells in HIV-2, a naturally contained human retroviral infection. Blood 2013; 121: 4330-4339.

    de Silva T, Leligdowicz A, Rowland-Jones S. Effect of HIV-2 infection on HIV-1 disease progression. N Engl J Med 2012; 367: 1961-1962; author reply 1962-1963.

    Reikie BA, Adams RC, Ruck CE, Ho K, Leligdowicz A, Pillay S, Naidoo S, Fortuno ES, 3rd, de Beer C, Preiser W, Cotton MF, Speert DP, Esser M, Kollmann TR. Ontogeny of Toll-like receptor mediated cytokine responses of South African infants throughout the first year of life. https://www.ncbi.nlm.nih.gov/pubmed/23028609PloS one 2012; 7: e44763.

    Zhang Y, Peng Y, Yan H, Xu K, Saito M, Wu H, Chen X, Ranasinghe S, Kuse N, Powell T, Zhao Y, Li W, Zhang X, Feng X, Li N, Leligdowicz A, Xu X, John M, Takiguchi M, McMichael A, Rowland-Jones S, Dong T. Multilayered defense in HLA-B51-associated HIV viral control. J Immunol 2011; 187: 684-691.

    Leligdowicz A, Onyango C, Yindom LM, Peng Y, Cotten M, Jaye A, McMichael A, Whittle H, Dong T, Rowland-Jones S. Highly avid, oligoclonal, early-differentiated antigen-specific CD8+ T cells in chronic HIV-2 infection. Eur J Immunol 2010; 40: 1963-1972.

    Leligdowicz A, Feldmann J, Jaye A, Cotten M, Dong T, McMichael A, Whittle H, Rowland-Jones S. Direct relationship between virus load and systemic immune activation in HIV-2 infection. J Infect Dis 2010; 201: 114-122.

    Yindom LM, Leligdowicz A, Martin MP, Gao X, Qi Y, Zaman SM, van der Loeff MS, van Tienen C, Jaye A, Aveika A, Worwui A, Diatta M, Vincent T, Whittle HC, Rowland-Jones SL, Walton R, Carrington M. Influence of HLA class I and HLA-KIR compound genotypes on HIV-2 infection and markers of disease progression in a Manjako community in West Africa. J Virol 2010; 84: 8202-8208.

    van der Loeff MF, Larke N, Kaye S, Berry N, Ariyoshi K, Alabi A, van Tienen C, Leligdowicz A, Sarge-Njie R, da Silva Z, Jaye A, Ricard D, Vincent T, Jones SR, Aaby P, Jaffar S, Whittle H. Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village. Retrovirology 2010; 7: 46.

    Tienen C, van der Loeff MS, Zaman SM, Vincent T, Sarge-Njie R, Peterson I, Leligdowicz A, Jaye A, Rowland-Jones S, Aaby P, Whittle H. Two distinct epidemics: the rise of HIV-1 and decline of HIV-2 infection between 1990 and 2007 in rural Guinea-Bissau. J Acquir Immune Defic Syndr 2010; 53: 640-647.

    Onyango CO, Leligdowicz A, Yokoyama M, Sato H, Song H, Nakayama EE, Shioda T, de Silva T, Townend J, Jaye A, Whittle H, Rowland-Jones S, Cotten M. HIV-2 capsids distinguish high and low virus load patients in a West African community cohort. Vaccine 2010; 28 Suppl 2: B60-67. 6

    Jallow S, Vincent T, Leligdowicz A, De Silva T, Van Tienen C, Alabi A, Sarge-Njie R, Aaby P, Corrah T, Whittle H, Jaye A, Vanham G, Rowland-Jones S, Janssens W. Presence of a multidrug-resistance mutation in an HIV-2 variant infecting a treatment-naive individual in Caio, Guinea Bissau. Clin Infect Dis 2009; 48: 1790-1793.

    Feldmann J, Leligdowicz A, Jaye A, Dong T, Whittle H, Rowland-Jones SL. Downregulation of the T-cell receptor by human immunodeficiency virus type 2 Nef does not protect against disease progression. J Virol 2009; 83: 12968-12972.

    Leligdowicz A, Rowland-Jones S. Tenets of protection from progression to AIDS: lessons from the immune responses to HIV-2 infection. Expert review of vaccines 2008; 7: 319-331.

    Mendy ME, Kaye S, Le Roux E, Kirk GD, Jeng-Barry A, McConkey S, Cotten M, Kuniholm MH, Leligdowicz A, Hainaut P, Rowland-Jones S, Whittle H. Application of a novel, rapid, and sensitive oligonucleotide ligation assay for detection of cancer-predicting mutations in the precore and basal core promoter of hepatitis B virus. Journal of clinical microbiology 2008; 46: 2723-2730.

    Leligdowicz A, Yindom LM, Onyango C, Sarge-Njie R, Alabi A, Cotten M, Vincent T, da Costa C, Aaby P, Jaye A, Dong T, McMichael A, Whittle H, Rowland-Jones S. Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection. J Clin Invest 2007; 117: 3067-3074.

    Jensen ML, Dave S, Schim van der Loeff M, da Costa C, Vincent T, Leligdowicz A, Benn CS, Roth A, Ravn H, Lisse IM, Whittle H, Aaby P. Vaccinia scars associated with improved survival among adults in rural Guinea-Bissau. PloS one 2006; 1: e101.

    Leligdowicz A, Katwere M, Piloya T, Ronald A, Kambugu A, Katabira E. Challenges in diagnosing, treating and following patients presenting with central nervous system infections in a resource-limited setting. McGill journal of medicine : MJM : an international forum for the advancement of medical sciences by students 2006; 9: 39-48.

    Gill KK, Leligdowicz A, Luo M, Bielawny T, Brunham R, Plummer FA. Identification of four novel HLA-A alleles from an East African population by high-resolution sequence-based typing. Human immunology 2006; 67: 833-838.