title: Disposal of iNKT cell deficiency and an increase in expression of SLAM signaling factors characterizes sarcoidosis remission: a 4-year longitudinal study.
abstract: BACKGROUND
  Invariant NKT (iNKT) cells are regulatory lymphocytes that may be important in disorders with increased Th1 responses. We utilized a 4-year longitudinal observational study of iNKT cells and SLAM signaling pathway factors, which are important for iNKT development in patients with newly diagnosed sarcoidosis.
  
  
  METHODS
  Detailed clinical, functional, and radiographic evaluation and determination of iNKT peripheral blood cell counts and expression of SLAM signaling factors was carried out at presentation and after 3 months, 1 year, and 4 years of disease follow-up in 29 patients with pulmonary sarcoidosis. At presentation, we also evaluated the frequencies of pulmonary BALF iNKT cells. We also included 37 control subjects.
  
  
  RESULTS
  We demonstrated a marked deficiency of blood and lung iNKT cells and decreased expression of SLAM signaling factors in patients with newly diagnosed sarcoidosis. During 4 years of disease follow-up, there was a significant increase in blood iNKT cell numbers and in expression of SLAM signaling factors, mainly SLAMF1, SLAMF6, and FYN. This increase clearly correlated with improvement in patients' clinical symptoms. At the 4-year endpoint, the disease had gone into remission in the great majority of patients and thus also iNKT cell deficiency. Moreover, at the 4-year endpoint iNKT level reached the iNKT level of the control subjects.
  
  
  CONCLUSIONS
  Our longitudinal study showed that a disposal of iNKT deficiency in parallel with an increase in expression of SLAM signaling factors characterizes the clinical remission of sarcoidosis.
authors.forename: Katarina
authors.initials: K
authors.lastname: Osolnik
authors.forename: Matija
authors.initials: M
authors.lastname: Rijavec
authors.forename: Peter
authors.initials: P
authors.lastname: Korosec
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis*; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D012075:Remission, Spontaneous; D012507:Sarcoidosis / Q000175:diagnosis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; C000604060:SLAMF6 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1