title: The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies: a prospective study.
abstract: The underlying cause of neutropenia may be difficult to determine due to similar clinical presentation in many neutropenic conditions. The neutrophil protein hCAP-18 (pro-LL-37) is a major component of neutrophil secondary granules and in this prospective study we assessed the use of hCAP-18 levels in blood plasma for differential diagnosis of neutropenic patients (n = 133) of various aetiologies. Plasma levels of hCAP-18 were determined using immunoblot and ELISA. Patients with severe congenital neutropenia (n = 23) presented with the lowest levels of plasma hCAP-18 and differential diagnostic accuracy revealed high sensitivity (100%) and specificity (98.8%) for hCAP-18 ELISA. The correlation coefficient of the hCAP-18 ELISA versus immunoblotting was (R = 0.831) and that of the peptide LL-37 ELISA versus immunoblotting was (R = 0.405) (P < 0.001). Plasma hCAP-18 levels thus displayed high diagnostic value in differential diagnosis of chronic neutropenia. Neutropenic patients with Shwachman-Diamond syndrome, Barth syndrome, Cohen syndrome, acute myeloid leukaemia and specific granule deficiency presented with reduced plasma hCAP-18 levels as well. The blood plasma level of hCAP-18 was thus low in conditions in which the neutrophil antibacterial propeptide hCAP-18 is deficient, i.e. severe congenital neutropenia and neutrophil-specific granule deficiency, and in conditions in which bone marrow myelopoiesis is negatively affected.
authors.affiliation: 1] Division of Paediatric Dentistry, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden [2] School and Hospital of Stomatology, Peking University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Carlsson
authors.affiliation: Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jenny M T
authors.initials: JM
authors.lastname: Karlsson-Sjöberg
authors.affiliation: The Granulocyte Research Laboratory, Department of Haematology, National University Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Borregaard
authors.affiliation: Division of Paediatric Dentistry, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Modéer
authors.affiliation: Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mats L
authors.initials: ML
authors.lastname: Andersson
authors.affiliation: Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Katrin L-A
authors.initials: KL
authors.lastname: Pütsep
mesh_terms: D000293:Adolescent; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D009503:Neutropenia / Q000097:blood* / Q000151:congenital / Q000175:diagnosis / Q000209:etiology*; D011446:Prospective Studies; D012372:ROC Curve; D055815:Young Adult; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins