title: Polyclonal expansion of large granular lymphocytes in common variable immunodeficiency - association with neutropenia.
abstract: Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency disease, characterized by low levels of circulating immunoglobulins and recurrent bacterial infections, particularly of the respiratory tract. T cell dysfunction is often present, and lymphoproliferative and autoimmune disorders as well as haematological cytopenias are frequently observed. In this study, we report a polyclonal expansion of large granular lymphocytes (LGL) in a substantial proportion of CVID patients, associated with splenomegaly, increased numbers of CD8(+) T cells, inverted CD4 : CD8 T cell ratios and neutropenia. CVID patients who had both increased numbers of LGL and granulocytopenia had elevated levels of soluble Fas ligand (sFasL). Our observations indicate that CVID may be added to the list of inflammatory diseases associated with increased numbers of LGL. Furthermore, our findings suggest common pathogenic mechanisms of granulocytopenia in CVID and lymphoproliferative disease of granular lymphocytes.
authors.affiliation: Section of Clinical Immunology and Infectious Diseases, Medical Department, Research Institute for Internal Medicine, Rikshospitalet University Hospital, Oslo, Norway. a.m.holm@klinmed.uio.no
authors.forename: A M
authors.initials: AM
authors.lastname: Holm
authors.forename: G
authors.initials: G
authors.lastname: Tjønnfjord
authors.forename: A
authors.initials: A
authors.lastname: Yndestad
authors.forename: K
authors.initials: K
authors.lastname: Beiske
authors.forename: F
authors.initials: F
authors.lastname: Müller
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.forename: S S
authors.initials: SS
authors.lastname: Frøland
mesh_terms: D000328:Adult; D000368:Aged; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000276:immunology*; D003594:Cytoplasmic Granules / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000648:ultrastructure; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology / Q000276:immunology*; D013163:Splenomegaly / Q000209:etiology / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000097:blood
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors