title: ACE and sIL-2R correlate with lung function improvement in sarcoidosis during methotrexate therapy.
abstract: BACKGROUND
  In sarcoidosis, the search for disease activity markers that correlate with treatment response is ongoing. The aim of this study was to investigate the pattern of two proposed markers, serum angiotensin-converting enzyme (ACE) and soluble IL-2 receptor (sIL-2R) during methotrexate (MTX) therapy in sarcoidosis patients.
  
  
  METHODS
  We analysed 114 sarcoidosis patients who used MTX for six months, consisting of a subgroup of 76 patients with a pulmonary indication for treatment and a subgroup of 38 patients with an extra-pulmonary indication. ACE and sIL-2R serum levels were measured at baseline and after six months of treatment. Correlation coefficients (R) and odds ratios (ORs) were calculated to study the correlation and predictive effect of serum ACE and sIL-2R levels for pulmonary improvement.
  
  
  RESULTS
  High baseline levels of ACE correlated significantly with lung function improvement after treatment (R = 0.45, p < 0.0001; stronger in the pulmonary subgroup R 0.57, p < 0.0001). ACE baseline levels >90 U/l predicted a 10% improvement in overall lung function (OR 3.55; CI 1.34-9.38), with the highest prediction level for 10% improvement in DLCO (OR 4.63; CI 1.23-17.4). After six months of MTX, mean ACE decreased with 17.2 U/l (p < 0.0001) and sIL-2R with 1850 pg/ml (p < 0.0001). Decreases in both ACE and sIL-2R correlated with an increase in lung function. The strongest correlation was found with change in DLCO in the pulmonary subgroup (ACE R = 0.63, P < 0.0001; sIL-2R R = 0.56, P < 0.0001).
  
  
  CONCLUSIONS
  Baseline and serial serum ACE and sIL-2R levels correlate well with lung function improvement during MTX treatment. Serial measurements of these biomarkers are helpful in monitoring treatment effects in sarcoidosis patients.
authors.affiliation: Interstitial Lung Diseases Center of Excellence, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands. Electronic address: a.vorselaars@antoniusziekenhuis.nl.
authors.forename: Adriane D M
authors.initials: AD
authors.lastname: Vorselaars
authors.affiliation: Interstitial Lung Diseases Center of Excellence, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands; Division of Heart and Lungs, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Coline H M
authors.initials: CH
authors.lastname: van Moorsel
authors.affiliation: Division of Heart and Lungs, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Zanen
authors.affiliation: Department of Clinical Chemistry, St. Antonius Hospital Nieuwegein, The Netherlands.
authors.forename: Henk J T
authors.initials: HJ
authors.lastname: Ruven
authors.affiliation: Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Anke M E
authors.initials: AM
authors.lastname: Claessen
authors.affiliation: Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Heleen
authors.initials: H
authors.lastname: van Velzen-Blad
authors.affiliation: Interstitial Lung Diseases Center of Excellence, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands; Division of Heart and Lungs, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Grutters
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D015375:Receptors, Interleukin-2 / Q000097:blood*; D012507:Sarcoidosis / Q000097:blood* / Q000188:drug therapy; D017565:Sarcoidosis, Pulmonary / Q000097:blood / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D007703:Peptidyl-Dipeptidase A; D008727:Methotrexate
keywords: ACE; Angiotensin converting enzyme; Methotrexate; Sarcoidosis; Soluble IL-2 receptor; sIL-2R