Davide Valentini1, Martin Rao2, Giovanni Ferrara3, Marc Perkins4, Ernest Dodoo2, Alimuddin Zumla5, Markus Maeurer6. 1. Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden; Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden. 2. Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden. 3. Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Solna, Sweden. 4. FIND, Geneva, Switzerland. 5. Centre for Clinical Microbiology, Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK. 6. Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden; Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden. Electronic address: markus.maeurer@ki.se.
Abstract
BACKGROUND: Understanding of humoral immune responses in tuberculosis (TB) is gaining interest, since B-cells and antibodies may be important in diagnosis as well as protective immune responses. High-content peptide microarrays (HCPM) are highly precise and reliable for gauging specific antibody responses to pathogens, as well as autoantigens. METHODS: An HCPM comprising epitopes spanning 154 proteins of Mycobacterium tuberculosis was used to gauge specific IgG antibody responses in sera of TB patients from Africa and South America. Open source software for general access to this method is provided. RESULTS: The IgG response pattern of TB patients differs from that of healthy individuals, with the molecular complexity of the antigens influencing the strength of recognition. South American individuals with or without TB exhibited a generally stronger serum IgG response to the tested M. tuberculosis antigens compared to their African counterparts. Individual M. tuberculosis peptide targets were defined, segregating patients with TB from Africa versus those from South America. CONCLUSIONS: These data reveal the heterogeneity of epitope-dependent humoral immune responses in TB patients, partly due to geographical setting. These findings expose a new avenue for mining clinically meaningful vaccine targets, diagnostic tools, and the development of immunotherapeutics in TB disease management or prevention.
BACKGROUND: Understanding of humoral immune responses in tuberculosis (TB) is gaining interest, since B-cells and antibodies may be important in diagnosis as well as protective immune responses. High-content peptide microarrays (HCPM) are highly precise and reliable for gauging specific antibody responses to pathogens, as well as autoantigens. METHODS: An HCPM comprising epitopes spanning 154 proteins of Mycobacterium tuberculosis was used to gauge specific IgG antibody responses in sera of TB patients from Africa and South America. Open source software for general access to this method is provided. RESULTS: The IgG response pattern of TB patients differs from that of healthy individuals, with the molecular complexity of the antigens influencing the strength of recognition. South American individuals with or without TB exhibited a generally stronger serum IgG response to the tested M. tuberculosis antigens compared to their African counterparts. Individual M. tuberculosis peptide targets were defined, segregating patients with TB from Africa versus those from South America. CONCLUSIONS: These data reveal the heterogeneity of epitope-dependent humoral immune responses in TB patients, partly due to geographical setting. These findings expose a new avenue for mining clinically meaningful vaccine targets, diagnostic tools, and the development of immunotherapeutics in TB disease management or prevention.