Longitudinal Immune Responses and Gene Expression Profiles in Type 1 Leprosy Reactions
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Leprosy, a chronic disease initiated by Mycobacterium leprae, is often complicated by acute inflammatory reactions. Although such episodes occur in at least 50 % of all leprosy patients and may cause irreversible nerve damage, no laboratory tests are available for early diagnosis or prediction of reactions. Since immune- and genetic host factors are critical in leprosy reactions, we hypothesize that identification of host-derived biomarkers correlated to leprosy reactions can provide the basis for new tests to facilitate timely diagnosis and treatment thereby helping to prevent tissue damage.
The longitudinal host response of a leprosy patient, who was affected by a type 1 reaction (T1R) after MDT-treatment, was studied in unprecedented detail, measuring cellular and humoral immunity and gene expression profiles to identify biomarkers specific for T1R.
Cytokine analysis in response to M. leprae revealed increased production of IFN-γ, IP-10, CXCL9, IL-17A and VEGF at diagnosis of T1R compared to before T1R, whereas a simultaneous decrease in IL-10 and G-CSF was observed at T1R. Cytokines shifts coincided with a reduction in known regulatory CD39+CCL4+ and CD25high T-cell subsets. Moreover, RNA expression profiles revealed that IFN-induced genes, (V)EGF, and genes associated with cytotoxic T-cell responses (GNLY, GZMA/B, PRF1) were upregulated during T1R, whereas expression of T-cell regulation-associated genes were decreased.
These data show that increased inflammation, vasculoneogenesis and cytotoxicity, perturbed T-cell regulation as well as IFN-induced genes play an important role in T1R and provide potential T1R-specific host biomarkers.
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- Longitudinal Immune Responses and Gene Expression Profiles in Type 1 Leprosy Reactions
Journal of Clinical Immunology
Volume 34, Issue 2 , pp 245-255
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- early diagnosis
- gene profiles
- leprosy reactions
- Industry Sectors
- Annemieke Geluk (1)
- Krista E. van Meijgaarden (1)
- Louis Wilson (1)
- Kidist Bobosha (1) (2)
- Jolien J. van der Ploeg-van Schip (1)
- Susan J. F. van den Eeden (1)
- Edwin Quinten (1)
- Karin Dijkman (1)
- Kees L. M. C. Franken (1)
- Elisabeth M. Haisma (1)
- Mariëlle C. Haks (1)
- Colette L. M. van Hees (3)
- Tom H. M. Ottenhoff (1)
- Author Affiliations
- 1. Department of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
- 2. Armauer Hansen Research Institute, Addis Ababa, Ethiopia
- 3. Department of Dermatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands