title: Immunodeficiency in alpha-mannosidosis: a matched case-control study on immunoglobulins, complement factors, receptor density, phagocytosis and intracellular killing in leucocytes.
abstract: Patients with the autosomal recessive lysosomal storage disease alpha-mannosidosis suffer from recurrent infections. To study the mechanisms of this immunodeficiency, six patients were matched against six healthy controls and their humoral and cellular immunocompetence investigated. No differences in the number of circulating leucocytes including B-cells, levels of immunoglobulin main classes, nor IgG subclasses were observed. However, post-immunisation serum levels of specific antibodies against poliovirus, diphtheria toxin and tetanus toxin were significantly reduced. In patients, the density of the complement-binding receptor CD11b and the Fc-receptor CD16 was significantly enhanced on monocytes and polymorphonuclear neutrophils (PMN) and the number of phagocytosing PMN was significantly increased in the presence of pooled human serum. This was not observed in the presence of autologous serum, indicating altered opsonic properties. Also in normal PMN, phagocytosis was inhibited by a factor in the serum from the patients. Despite maintained oxidative burst, patient PMN demonstrated insufficient intracellular bacterial killing.
  
  
  CONCLUSIONS
  Our data indicate that patients with alpha-mannosidosis have an immunodeficiency at both the humoral and cellular level.
authors.affiliation: Department of Medicine, University Hospital Tromsø, Norway. dag.malm@rito.no
authors.forename: D
authors.initials: D
authors.lastname: Malm
authors.forename: D S
authors.initials: DS
authors.lastname: Halvorsen
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: H
authors.initials: H
authors.lastname: Sjursen
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D003165:Complement System Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000150:complications*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D010587:Phagocytosis; D011951:Receptors, Complement / Q000097:blood; D008363:alpha-Mannosidosis / Q000097:blood / Q000150:complications / Q000276:immunology*
chemical_list: D007136:Immunoglobulins; D011951:Receptors, Complement; D003165:Complement System Proteins