title: Longitudinal immune responses and gene expression profiles in type 1 leprosy reactions.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands, ageluk@lumc.nl.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Geluk
authors.forename: Krista E
authors.initials: KE
authors.lastname: van Meijgaarden
authors.forename: Louis
authors.initials: L
authors.lastname: Wilson
authors.forename: Kidist
authors.initials: K
authors.lastname: Bobosha
authors.forename: Jolien J
authors.initials: JJ
authors.lastname: van der Ploeg-van Schip
authors.forename: Susan J F
authors.initials: SJ
authors.lastname: van den Eeden
authors.forename: Edwin
authors.initials: E
authors.lastname: Quinten
authors.forename: Karin
authors.initials: K
authors.lastname: Dijkman
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Haisma
authors.forename: Mariëlle C
authors.initials: MC
authors.lastname: Haks
authors.forename: Colette L M
authors.initials: CL
authors.lastname: van Hees
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
mesh_terms: D000293:Adolescent; D000942:Antigens, Bacterial / Q000276:immunology; D015415:Biomarkers; D001706:Biopsy; D016207:Cytokines / Q000096:biosynthesis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D056724:Immunity, Humoral / Q000235:genetics; D016130:Immunophenotyping; D007918:Leprosy / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D008297:Male; D009166:Mycobacterium leprae / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome
chemical_list: D000942:Antigens, Bacterial; D015415:Biomarkers; D016207:Cytokines; D012333:RNA, Messenger