title: Defect of lck in a patient with common variable immunodeficiency.
abstract: Common variable immunodeficiency (CVID) is a congenital immunological disorder characterized by defective antibody production with normal count of peripheral B lymphocytes. The basic immunologic defects that leads to CVID are still unknown, however, a proportion of CVID is suggested to be caused by decreased CD4+ helper T cell activity. In addition, recent reports indicate that a defect of T cell receptor (TCR)-associated signaling molecules results in congenital immune deficiency in human. In the present study, we investigated lck, a signaling molecule downstream of TCR, in a patient with CVID plus CD4 lymphopenia, and found an aberrantly spliced lck transcript lacking the entire exon 7 associated with the decrease in the expression of lck protein. An identical splicing abnormality has been previously demonstrated in a case of severe combined immunodeficiency with selective CD4 lymphopenia, although the case showed almost complete loss of the expression of lck protein. Considering these findings, the aberrant splicing of lck gene is suggested to be correlated, at least with a subset of congenital immunodeficiency plus CD4 lymphopenia.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sawabe
authors.forename: T
authors.initials: T
authors.lastname: Horiuchi
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: K
authors.initials: K
authors.lastname: Nakahara
authors.forename: S I
authors.initials: SI
authors.lastname: Harashima
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: S
authors.initials: S
authors.lastname: Nakano
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000328:Adult; D015153:Blotting, Western; D015704:CD4 Antigens / Q000096:biosynthesis; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D005091:Exons; D006801:Humans; D016130:Immunophenotyping; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics* / Q000378:metabolism; D008231:Lymphopenia / Q000378:metabolism; D008297:Male; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D015704:CD4 Antigens; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)