title: Plasma Levels of Neopterin and C-Reactive Protein (CRP) in Tuberculosis (TB) with and without HIV Coinfection in Relation to CD4 Cell Count.
abstract: BACKGROUND
  While the risk of TB is elevated in HIV-positive subjects with low CD4 cell counts, TB may in itself be associated with CD4 lymphocytopenia. We investigated markers of immune activation (neopterin) and inflammation (CRP) in TB patients with and without HIV coinfection and their association with CD4 cell levels, and determined their predictive capacity as alternative markers of advanced immunosuppression.
  
  
  METHODS
  Participants selected from a cohort of adults with TB at Ethiopian health centers (195 HIV+/TB+, 170 HIV-/TB+) and 31 controls were tested for plasma levels of neopterin and CRP. Baseline levels of neopterin and CRP were correlated to CD4 cell count before and after anti-TB treatment (ATT). The performance to predict CD4 cell strata for both markers were investigated using receiver operating curves.
  
  
  RESULTS
  Levels of both biomarkers were elevated in TB patients (neopterin: HIV+/TB+ 54 nmol/l, HIV-/TB+ 23 nmol/l, controls 3.8 nmol/l; CRP: HIV+/TB+ 36 μg/ml, HIV-/TB+ 33 μg/ml, controls 0.5 μg/ml). Neopterin levels were inversely correlated (-0.53, p<0.001) to CD4 cell count, whereas this correlation was weaker for CRP (-0.25, p<0.001). Neither of the markers had adequate predictive value for identification of subjects with CD4 cell count <100 cells/mm3 (area under the curve [AUC] 0.64 for neopterin, AUC 0.59 for CRP).
  
  
  CONCLUSIONS
  Neopterin levels were high in adults with TB, both with and without HIV coinfection, with inverse correlation to CD4 cell count. This suggests that immune activation may be involved in TB-related CD4 lymphocytopenia. However, neither neopterin nor CRP showed promise as alternative tests for immunosuppression in patients coinfected with HIV and TB.
authors.affiliation: Infectious Disease Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Skogmar
authors.affiliation: Department of Medical Microbiology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.|Department of Clinical Microbiology and Infectious diseases, Kalmar County Hospital, Kalmar, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schön
authors.affiliation: Infectious Disease Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.|Ministry of Health, Addis Ababa, Ethiopia.
authors.forename: Taye Tolera
authors.initials: TT
authors.lastname: Balcha
authors.affiliation: Medical Microbiology, Department of Laboratory Medicine Malmö, Lund University, Malmö, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Sturegård
authors.affiliation: Department of Laboratory Medicine, Lund University, Lund, Sweden.|Department of Microbiology, Tumor and Cell biology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Jansson
authors.affiliation: Infectious Disease Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Björkman
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D060085:Coinfection / Q000097:blood* / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D008231:Lymphopenia / Q000097:blood / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D008297:Male; D019798:Neopterin / Q000097:blood; D011446:Prospective Studies; D012189:Retrospective Studies; D014376:Tuberculosis / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D019798:Neopterin; D002097:C-Reactive Protein