Journal of Clinical Immunology

, Volume 34, Issue 2, pp 245–255

Longitudinal Immune Responses and Gene Expression Profiles in Type 1 Leprosy Reactions

  • Annemieke Geluk
  • Krista E. van Meijgaarden
  • Louis Wilson
  • Kidist Bobosha
  • Jolien J. van der Ploeg-van Schip
  • Susan J. F. van den Eeden
  • Edwin Quinten
  • Karin Dijkman
  • Kees L. M. C. Franken
  • Elisabeth M. Haisma
  • Mariëlle C. Haks
  • Colette L. M. van Hees
  • Tom H. M. Ottenhoff
Original Research

DOI: 10.1007/s10875-013-9979-x

Cite this article as:
Geluk, A., van Meijgaarden, K.E., Wilson, L. et al. J Clin Immunol (2014) 34: 245. doi:10.1007/s10875-013-9979-x

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Biomarker early diagnosis gene profiles leprosy reactions T1R 

Supplementary material

10875_2013_9979_MOESM1_ESM.doc (4.6 mb)
ESM 1(DOC 4.64 MB)

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • 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
  1. 1.Department of Infectious DiseasesLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Armauer Hansen Research InstituteAddis AbabaEthiopia
  3. 3.Department of Dermatology, Erasmus MCUniversity Medical CenterRotterdamThe Netherlands

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