Longitudinal immune responses and gene expression profiles in type 1 leprosy reactions

J Clin Immunol. 2014 Feb;34(2):245-55. doi: 10.1007/s10875-013-9979-x. Epub 2013 Dec 27.


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 CD25(high) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, Bacterial / immunology
  • Biomarkers
  • Biopsy
  • Cytokines / biosynthesis
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Immunity, Cellular / genetics
  • Immunity, Humoral / genetics
  • Immunophenotyping
  • Leprosy / diagnosis
  • Leprosy / genetics*
  • Leprosy / immunology*
  • Male
  • Mycobacterium leprae / immunology
  • RNA, Messenger / genetics
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transcriptome*


  • Antigens, Bacterial
  • Biomarkers
  • Cytokines
  • RNA, Messenger