title: Is CXCL10/CXCR3 axis overexpression a better indicator of leprosy type 1 reaction than inducible nitric oxide synthase?
abstract: OBJECTIVE
  Leprosy type 1 reactions (T1R) are acute episodes of immune exacerbation that are a major cause of inflammation and nerve damage. T1R are diagnosed clinically and supported by histopathology. No laboratory marker is currently available that can accurately predict a T1R. Increased plasma and tissue expression of inducible nitric oxide synthase (i-NOS) and chemokine CXCL10 have been demonstrated in T1R. We studied the gene expression and immunoexpression of i-NOS, CXCL10 and its receptor CXCR3 in clinically and histopathologically confirmed patients with T1R and compared with non-reactional leprosy patients to understand which biomarker has better potential in distinguishing reaction from non-reaction.
  
  
  METHODS
  Gene expression of i-NOS, CXCL10 and CXCR3 was studied in 30 skin biopsies obtained from patients with borderline tuberculoid (BT), mid-borderline (BB) and borderline lepromatous (BL) leprosy with and without T1R by real-time PCR. Further validation was done by immunohistochemical expression on 60 borderline leprosy biopsies with and without T1R.
  
  
  RESULTS
  Of the 120 patients histopathological evaluation confirmed T1R in 65 (54.2%) patients. CXCR3 gene expression was significantly (P<0.05) higher in BT- and BB-T1R patients compared to those without T1R. The CXCL10 gene expression was significantly higher (P<0.05) in BB leprosy with T1R but the difference was not significant in patients with BT with or without T1R. Immunoexpression for CXCR3 was significant in both BB-T1R and BB (P<0.001) and BT and BT-T1R (P<0.001). Immunoexpression of CXL10 was significant only in differentiating BB from BB-T1R leprosy (P<0.01) and not the BT cases. i-NOS immunoexpression was not useful in differentiating reactional from non-reactional leprosy.
  
  
  CONCLUSIONS
  Both CXCL10 and CXCR3 appeared to be useful in differentiating T1R reaction in borderline leprosy while CXCR3 alone differentiated BT from BT-T1R. CXCR3 may be a potentially useful immunohistochemical marker to predict an impending T1R.
authors.forename: Ira
authors.initials: I
authors.lastname: Sharma
authors.affiliation: National Institute of Pathology (ICMR), New Delhi, India.
authors.forename: Avninder
authors.initials: A
authors.lastname: Singh
authors.forename: Ashwani K
authors.initials: AK
authors.lastname: Mishra
authors.forename: L C
authors.initials: LC
authors.lastname: Singh
authors.forename: V
authors.initials: V
authors.lastname: Ramesh
authors.forename: Sunita
authors.initials: S
authors.lastname: Saxena
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D003430:Cross-Sectional Studies; D006801:Humans; D007918:Leprosy / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054367:Receptors, CXCR3; D052247:Nitric Oxide Synthase Type II
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