title: Rapid diagnosis of FHL3 by flow cytometric detection of intraplatelet Munc13-4 protein.
abstract: Familial hemophagocytic lymphohistiocytosis (FHL) is a potentially lethal genetic disorder of immune dysregulation that requires prompt and accurate diagnosis to initiate life-saving immunosuppressive therapy and to prepare for hematopoietic stem cell transplantation. In the present study, 85 patients with hemophagocytic lymphohistiocytosis were screened for FHL3 by Western blotting using platelets and by natural killer cell lysosomal exocytosis assay. Six of these patients were diagnosed with FHL3. In the acute disease phase requiring platelet transfusion, it was difficult to diagnose FHL3 by Western blot analysis or by lysosomal exocytosis assay. In contrast, the newly established flow cytometric analysis of intraplatelet Munc13-4 protein expression revealed bimodal populations of normal and Munc13-4-deficient platelets. These findings indicate that flow cytometric detection of intraplatelet Munc13-4 protein is a sensitive and reliable method to rapidly screen for FHL3 with a very small amount of whole blood, even in the acute phase of the disease.
authors.affiliation: Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Murata
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasumi
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Shirakawa
authors.forename: Kazushi
authors.initials: K
authors.lastname: Izawa
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Sakai
authors.forename: Junya
authors.initials: J
authors.lastname: Abe
authors.forename: Naoko
authors.initials: N
authors.lastname: Tanaka
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kawai
authors.forename: Koichi
authors.initials: K
authors.lastname: Oshima
authors.forename: Megumu
authors.initials: M
authors.lastname: Saito
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Hisanori
authors.initials: H
authors.lastname: Horiuchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020014:K562 Cells; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C507969:UNC13D protein, human