Longitudinal immune profiles in type 1 leprosy reactions in Bangladesh, Brazil, Ethiopia and Nepal

BMC Infectious Diseases

Annemieke Geluk²  Deanna A. Hagge⁴  Tom H.M. Otttenhoff²  Linda Oskam¹  John S. Spencer⁵  Abraham Aseffa³  Kees L.M.C. Franken²  Yonas Bekele³  Washington Carvalho¹  Janaina Lobato¹  Luiz R. Goulart¹  Hymonti Dey⁶  Senjuti Kabir⁶  Louis Wilson⁶  Susan J.F. van den Eeden²  Krista E. van Meijgaarden²  Chhatra B. Kunwar⁴  Pratibha Thapa⁴  Isabela M. Goulart¹  Jolien J. van der Ploeg-van Schip²  Kidist Bobosha³  Sayera Banu⁶  Saraswoti Khadge⁴ 

[1] National Reference Center for Sanitary Dermatology and Leprosy, Faculty of Medicine, Federal University of Uberlandia, Minas Gerais, Brazil;Dept. of Infectious Diseases, Leiden University Medical Center (LUMC), PO Box 9600, Leiden, 2300 RC, The Netherlands;Armauer Hansen Research Institute, Addis Ababa, Ethiopia;Mycobacterial Research Laboratories, Anandaban Hospital, Kathmandu, Nepal;Dept. of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, USA;International Center for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh

关键词: Reactions;    Ratios;    M. leprae;    Leprosy;    Diagnostics;    Cytokines;    Biomarkers;   

Others  :  1232742
DOI  :  10.1186/s12879-015-1128-0

 received in 2015-05-01, accepted in 2015-09-18,  发布年份 2015

【 摘 要 】

Background

Acute inflammatory reactions are a frequently occurring, tissue destructing phenomenon in infectious- as well as autoimmune diseases, providing clinical challenges for early diagnosis. In leprosy, an infectious disease initiated by Mycobacterium leprae (M. leprae), these reactions represent the major cause of permanent neuropathy. However, laboratory tests for early diagnosis of reactional episodes which would significantly contribute to prevention of tissue damage are not yet available.

Although classical diagnostics involve a variety of tests, current research utilizes limited approaches for biomarker identification. In this study, we therefore studied leprosy as a model to identify biomarkers specific for inflammatory reactional episodes.

Methods

To identify host biomarker profiles associated with early onset of type 1 leprosy reactions, prospective cohorts including leprosy patients with and without reactions were recruited in Bangladesh, Brazil, Ethiopia and Nepal. The presence of multiple cyto-/chemokines induced by M. leprae antigen stimulation of peripheral blood mononuclear cells as well as the levels of antibodies directed against M. leprae-specific antigens in sera, were measured longitudinally in patients.

Results

At all sites, longitudinal analyses showed that IFN-γ-, IP-10-, IL-17- and VEGF-production by M. leprae (antigen)-stimulated PBMC peaked at diagnosis of type 1 reactions, compared to when reactions were absent. In contrast, IL-10 production decreased during type 1 reaction while increasing after treatment. Thus, ratios of these pro-inflammatory cytokines versus IL-10 provide useful tools for early diagnosing type 1 reactions and evaluating treatment. Of further importance for rapid diagnosis, circulating IP-10 in sera were significantly increased during type 1 reactions. On the other hand, humoral immunity, characterized by M. leprae-specific antibody detection, did not identify onset of type 1 reactions, but allowed treatment monitoring instead.

Conclusions

This study identifies immune-profiles as promising host biomarkers for detecting intra-individual changes during acute inflammation in leprosy, also providing an approach for other chronic (infectious) diseases to help early diagnose these episodes and contribute to timely treatment and prevention of tissue damage.

【 授权许可】

   
2015 Khadge et al.

【 图 表 】

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