I. Immunodiagnostics of Leprosy:
- Identification of antigens and epitopes for T-cells that are essential to protective immunity or immunopathology.
- Identification and validation of disease-specific, genetic and immune host-derived biomarkersfor Mycobacterium leprae infection, leprosy disease and leprosy reactions
- Design, development and evaluation of biomarker-based diagnostic tests that can be applied in field-settings.
In August 2016 we conducted a pilot study for a new, user-friendly test for diagnosis of leprosy in the Brazilian state of Pará located in the Brazilian Amazon, a region still highly endemic for leprosy. The new test developed at the LUMC can detect infection with the bacterium that causes leprosy at early stages before clinical signs are visible. It is important that the test can be conducted in people's homes because those who are at high risk of developing leprosy often don’t have the means to attend specialized clinics. Besides interruption of transmission, the incorporation of this user-friendly field test will allow early treatment with antibiotics to prevent irreversible nerve damage and handicaps.
II. Development of Vaccines for Tuberculosis:
For this research aim, a mouse Mtb challenge model was set-up at the LUMC MLIII facility. In this model, both acute as well as chronic/long term Mtb infection are studied using ‘humanized, HLA class-I and HLA class-II transgenic mice to assess the potential of candidate antigens in the context of HLA polymorphism.
Contributions to the field:
- Identification of M.leprae unique antigens that can be used as biomarker tools to discriminate the degree of M.leprae exposure and thus the risk of transmission of infection.
- Identification of disease-specific biomarkers for application in tests for diagnosis of early (preclinical) leprosy and monitoring the response to treatment.
- Identification of differential gene expression during leprosy reactions
- Identification of various HLA-restricted M. tuberculosisT cell epitopes
- Design and development of a field-friendlydiagnostic assay for leprosy and tuberculosis
van Hooij, A, EM Tjon Kon Fat, R Richardus, SJF van den Eeden, Louis Wilson, CJ de Dood, R Faber, K Alam, JH RichardusPLAM Corstjens and A Geluk. 2016. Quantitative lateral flow strip assays as user-friendly tools to detect biomarker profiles for leprosy. Sci. Rep. 6:34260;doi:10.1038/srep34260 (2016).,
Corstjens, PLAM, van Hooij, A., Tjon Kon Fat, EM, van den Eeden, SJF, Wilson, L and A Geluk. 2016. Field-friendly test for monitoring multiple immune response markers during onset and treatment of exacerbated immunity in leprosy. Clin.Vaccine Immunol. 23(6):515-519.
Roset Bahmanyar, E, C Smith, P Brennan, R Cummings, M Duthie, JH Richardus, P Saunderson, T Shwe, S Rosen and A Geluk. 2016. Leprosy diagnostic test development as a prerequisite towards elimination: requirements from the user’s perspective. PLoS NTD doi :10.1371/journal.pntd.0004331.
Khadge, S., S. Banu, K. Bobosha, van der Ploeg-van Schip JJ, I. M. Goulart, P. Thapa, C. B. Kunwar, K. E. van Meijgaarden, S. J. van den Eeden, L. Wilson, S. Kabir, H. Dey, L. R. Goulart, J. Lobato, W. Carvalho, Y. Bekele, K. L. Franken, A. Aseffa, J. S. Spencer, L. Oskam, T. H. Otttenhoff, D. A. Hagge, and A. Geluk. 2015. Longitudinal immune profiles in type 1 leprosy reactions in Bangladesh, Brazil, Ethiopia and Nepal. BMC. Infect. Dis. 15: 477.
Corstjens, PLAM, EM Tjon Kon Fat, CJ de Dood, JJ van der Ploeg-van Schip, KLMC Franken, NN Chegou, JS Sutherland, R Howe, A Mihret, D Kassa, M van der Vyver, J Sheehama, A Crampin, H Mayanja-Kizza, THM Ottenhoff, G Walzl and A Geluk. 2015. Multi-center evaluation of a user-friendly lateral flow assay to determine IP-10 and CCL4 levels in blood of TB and non-TB cases in Africa. Clinical Biochemistry. S0009-9120(15)00393-8 [pii];10.1016/ j.clinbiochem.2015.08.013 [doi].
Geluk A, KE van Meijgaarden, L Wilson, K Bobosha, JJ van der Ploeg- van Schip, Susan JF van den Eeden, E Quinten, K Dijkman, KLMC Franken, I Haisma, MC Haks, CLM van Hees, and THM Ottenhoff. 2014. Longitudinal immune responses and gene expression profiles associated with type 1 leprosy reactions. J. Clinical Immunology. 34: 245-255.
Bobosha, K, EM Tjon Kon Fat, SJF van den Eeden, Y Bekele, JJ van der Ploeg-van Schip, CJ de Dood, K Dijkman, KLMC Franken, L Wilson, A Aseffa , JS Spencer, THM Ottenhoff, PLAM Corstjens and A. Geluk. 2014. Field-Evaluation of a New Lateral Flow Assay for Detection of Cellular and Humoral Immunity against Mycobacterium leprae. PLoS Negl Trop Dis 8(5): e2845. doi:10.1371/journal.pntd. 0002845.
Commandeur, S, SJF van den Eeden, K Dijkman, SO Clark, KE van Meijgaarden, L Wilson, KLMC Franken, A Williams, D Christensen, THM Ottenhoff and A Geluk. 2014. The in vivo expressedMycobacterium tuberculosis (IVE-TB) antigen Rv2034 induces CD4+ T-cells that protect against pulmonary infection in HLA-DR transgenic mice and guinea pigs. Vaccine 32: 3580-3588.
Geluk, A., K Bobosha, JJ van der Ploeg-van Schip, JS Spencer, S Banu, M Brandao Martins, S Cho, KLMC Franken, HJ Kim, Y Bekele, MKM Uddin, SA Hadi, A Aseffa, MCV Pessolani, GMB Pereira, HM Dockrell, and THM Ottenhoff. 2012. New biomarkers for Mycobacterium lepraeInfection applicable in areas highly endemic for Leprosy. J. Immunol. 188: 4782-4791.
Geluk, A, SJF van den Eeden, K Dijkman, L Wilson, HJ Kim, K Franken, MCV Pessolani, JS Spencer, GMB Pereira, and THM Ottenhoff. 2011. In vivo cytotoxic function of the ML1419c HLA-A*0201-restricted T cell epitope of Mycobacterium leprae. J. Immunol. 187: 1393–1402.
Corstjens, PLAM, CJ de Dood, JJ Ploeg-van Schip, CC Wiesmeijer, T Riuttamäki-Rantanen, KE van Meijgaarden, JS Spencer, HJ Tanke, THM Ottenhoff, A Geluk. 2011. Lateral flow assay for simultaneous detection of cellular- and humoral immune responses. Clinical Biochemistry 44: 1241-1246.
Geluk, A, and THM Ottenhoff. 2006. HLA and leprosy in the pre- and postgenomic eras. Hum. Immunol.67:439-445.
Geluk, A, MR Klein, K Franken, KE van Meijgaarden, B Wieles, KC Pereira, S Bührer-Sékula, PR Klatser, DL Williams, J Spencer, P J Brennan, EP Sampaio, and THM Ottenhoff. 2005. A postgenomic approach to identify novel antigens of Mycobacterium leprae for improved immunodiagnosis of M. leprae infection. Inf. Immun. 73: 5636-5644.
Geluk, A, KE van Meijgaarden, KLMC Franken, S D’Souza, A Necker, K Huygen, and THM Ottenhoff. 2000. Identification of a major epitope of Mycobacterium tuberculosis Ag85B that is recognized by HLA-A*0201-restricted CD8+ T cells in HLA-transgenic mice and humans. J. Immunol. 165:6463-6471.
Geluk, A, V Taneja, KE van Meijgaarden, E Zanelli, C Abou-Zeid, JER Thole, RRP de Vries, CS David, and THM Ottenhoff. 1998. Identification of HLA class II-restricted determinants of M. tuberculosis-derived proteins using HLA-transgenic, class II deficient mice. Proc. Natl. Acad. Sci.USA 95:10797-10802.
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Following my masters in Chemistry at the University of Leiden and the University of Virginia, Charlottesville, USA, I did my PhD in Immunology at the LUMC, Dept. IHB (HLA-DR3/ Peptide/ T cell Interactions) and worked at Cytel Corporation, San Diego, USA. I received postdoctoral training at the Mayo Clinic, Rochester, MN, USA and was acknowledged a 5-year fellowship by the Royal Dutch Academy of Sciences during which period I focused on the immunology of leprosy and tuberculosis, particularly the identification of HLA-restricted T cell (epitopes) that are essential to protective immunity or immunopathology and biomarkers for development of immunodiagnostics.
My current research focusses on Immunodiagnostics of Leprosy including basic-, translational-, applied- as well as field research and Tuberculosis Vaccine Development using HLA transgenic mouse models. Currently, I am a member of the steering committee of the IDEAL consortium (Initiative for Diagnostic and Epidemiological Assays for Leprosy) and have designed and coordinated several large-scale, multi-center studies in e.g. Bangladesh, Brazil, Ethiopia and Nepal.
Grants were received from the Royal Netherlands Academy of Sciences, the Commission of European Communities, the Netherlands Leprosy Relief Foundation (NLR), the Turing Foundation, the Q.M. Gastmann-Wichers Foundation, the Order of Malta-Grants-for-Leprosy-Research (MALTALEP), the Heiser Program for Research in Leprosy in The New York Community Trust, The Novartis Foundation for Sustainable Development and EDCTP (European and Developing Countries Clinical Trials Partnership).
Leids Universitair Medisch Centrum
2333 ZA Leiden
Tel: +31 (0)71 52 61974
2300 RC Leiden