title: Endogenously activated interleukin-4 differentiates disease progressors and non-progressors in tuberculosis susceptible families: a 2-year biomarkers follow-up study.
abstract: OBJECTIVE
  Dynamic cytokine profiles from endogenously activated T cells in transit from lymph node to the infected sites via the blood compartment after recent exposure to Mycobacterium tuberculosis may differentiate disease progressors from non-disease progressors in a BCG-vaccinated population.
  
  
  METHODS
  Household contacts (N = 107) from families with (six families) or without (14 families) secondary cases were assessed for Types 1 and 2 cytokines serially in plasma of whole blood cultures without exogenous stimulation. "ARMS" PCR was carried out for detection of single nucleotide polymorphism T/A in IFN-γ +874.
  
  
  RESULTS
  In the absence of IFN-γ expansion, raised IL-4 at 6 months was associated with disease progression in TB-susceptible families. Resistant families on the other hand showed overrepresentation of IFN-γ +874 A allele and expansion of IFN-γ secreting cells at 6 months followed by contraction at 12 months.
  
  
  CONCLUSIONS
  Six months may be an important checkpoint for biomarker assessment in high-risk individuals post-exposure.
authors.affiliation: Department of Pathology and Microbiology, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan. rabia.hussain@aku.edu
authors.forename: Rabia
authors.initials: R
authors.lastname: Hussain
authors.forename: Najeeha
authors.initials: N
authors.lastname: Talat
authors.forename: Ambreen
authors.initials: A
authors.lastname: Ansari
authors.forename: Firdaus
authors.initials: F
authors.lastname: Shahid
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hasan
authors.forename: Ghaffar
authors.initials: G
authors.lastname: Dawood
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D008297:Male; D032541:Mass Vaccination; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011110:Polymorphism, Genetic; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D058408:Th1-Th2 Balance; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D015847:Interleukin-4; D007371:Interferon-gamma