title: Applying T-cell receptor excision circles and immunoglobulin κ-deleting recombination excision circles to patients with primary immunodeficiency diseases.
abstract: BACKGROUND
  Biomarkers of T-cell receptor excision circles (TRECs) and immunoglobulin κ-deleting recombination excision circles (KRECs) reflect naïve T and B cell emigrants. This study assessed the biomarkers in patients with primary immunodeficiency diseases (PIDs) to determine the lymphocyte output disturbance and the correlation to lymphocytes.
  
  
  METHODS
  A standard plasmid was constructed to calculate TRECs and KRECs in 250 ng genomic DNA from whole blood of PIDs patients. These were correlated to naïve and memory lymphocytes for further classification and adequate treatment.
  
  
  RESULTS
  In 69 studied patients, the low TRECs mainly included those with severe combined T and B immunodeficiency (SCID, 7/8), combined immunodeficiency (CID, 4/4), and common variable immunodeficiency (CVID, 6/7). The diminished KRECs was in SCID (4/8), CID (4/4), CVID (7/7), Bruton's tyrosine kinase mutation (Btk, 3/4), anti-B cell deletion (by anti-CD20 antibody in 1), and Behçet syndrome under steroid treatment (1). The TRECs and KRECs positively correlated to absolute naïve T (CD4 + CD45RA+) and naïve B (CD19 + CD27-), and to memory B (CD19 + CD27+) numbers, respectively.
  
  
  CONCLUSIONS
  This study validates that low TRECs and KRECs values reflect low naïve T and B lymphocytes in 'combined immunodeficiencies' and in some CVID patients with the potential to develop the CID phenotype.
authors.affiliation: Primary Immunodeficiency Care And Research (PICAR) Institute, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Taoyuan , Taiwan.
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Lee
authors.forename: Jing-Long
authors.initials: JL
authors.lastname: Huang
authors.forename: Syh-Jae
authors.initials: SJ
authors.lastname: Lin
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Yeh
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Chen
authors.forename: Liang-Shiou
authors.initials: LS
authors.lastname: Ou
authors.forename: Tsung-Chieh
authors.initials: TC
authors.lastname: Yao
authors.forename: Tang-Her
authors.initials: TH
authors.lastname: Jaing
authors.forename: Ying-Fan
authors.initials: YF
authors.lastname: Shih
authors.forename: Tzu-Ying
authors.initials: TY
authors.lastname: Tseng
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D015704:CD4 Antigens / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000235:genetics / Q000276:immunology*; D005260:Female; D019672:Genes, T-Cell Receptor; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007156:Immunologic Memory; D007223:Infant; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D060152:V(D)J Recombination; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; D015415:Biomarkers; D015704:CD4 Antigens; D007145:Immunoglobulin kappa-Chains; D011948:Receptors, Antigen, T-Cell; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D017493:Leukocyte Common Antigens
keywords: Combined immunodeficiency (CID); T-cell receptor excision circles (TRECs); common variable immunodeficiency (CVID); immunoglobulin κ-deleting recombination excision circles (KRECs); primary immunodeficiency diseases (PIDs); severe combined T and B immunodeficiency (SCID)