title: Increased CXC ligand 10 levels and gene expression in type 1 leprosy reactions.
abstract: Type 1 reaction (T1R) is a systemic inflammatory syndrome causing substantial morbidity in leprosy. T1R results from spontaneously enhanced cellular immunity in borderline types of leprosy, but there are no established laboratory markers for the reaction. Preliminary studies have identified elevated circulating CXC ligand 10 (CXCL10) during T1R. Correlation of CXCL10 with clinical T1R was studied in repeated serum specimens obtained before, during, and after T1R. CXCL10 gene expression was assessed in biopsy specimens taken before and during T1R, and sections were stained for the cytokine using monoclonal antibodies. Sequential serum specimens revealed elevation of circulating CXCL10 associated with episodes of T1R (P = 0.0001) but no evidence of an earlier, predictive change in the level of the chemokine. Reverse transcriptase (RT)-PCR revealed elevated expression of CXCL10 transcripts during T1R, but not in patients who did not have T1R. No significant correlation between CXCL10 and gamma interferon (IFN-γ) mRNA levels was observed. Immunohistochemical staining of the skin biopsy specimens suggested an overall increase in CXCL10 but did not identify a particular strongly staining population of leukocytes. Increased CXCL10 in lesions and serum is characteristic of T1R. CXCL10 measurement offers new possibilities for laboratory diagnosis and monitoring of T1R. Studies of the regulation of CXCL10 may provide insight into the mechanisms of T1R and identify potential new drug targets for treatment.
authors.affiliation: National Hansen's Disease Programs, 1770 Physician Park Dr., Baton Rouge, LA 70816, USA. DScollard@hrsa.gov
authors.forename: David M
authors.initials: DM
authors.lastname: Scollard
authors.forename: Meher V
authors.initials: MV
authors.lastname: Chaduvula
authors.forename: Alejandra
authors.initials: A
authors.lastname: Martinez
authors.forename: Natalie
authors.initials: N
authors.lastname: Fowlkes
authors.forename: Indira
authors.initials: I
authors.lastname: Nath
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Stryjewska
authors.forename: Michael T
authors.initials: MT
authors.lastname: Kearney
authors.forename: Diana L
authors.initials: DL
authors.lastname: Williams
mesh_terms: D000328:Adult; D001706:Biopsy; D054357:Chemokine CXCL10 / Q000096:biosynthesis* / Q000097:blood*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D007918:Leprosy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum / Q000737:chemistry; D012867:Skin / Q000276:immunology / Q000473:pathology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D007371:Interferon-gamma