Immunodeficiency in alpha-mannosidosis: a matched case-control study on immunoglobulins, complement factors, receptor density, phagocytosis and intracellular killing in leucocytes

Patients with the autosomal recessive lysosomal storage disease alpha-manno sidosis suffer from recurrent infections. To study the mechanisms of this i mmunodeficiency, six patients were matched against six healthy controls and their humoral and cellular immunocompetence investigated. No differences i n the number of circulating leucocytes including B-cells? levels of immunog lobulin main classes, nor IgG subclasses were observed. However, post-immun isation serum levels of specific antibodies against poliovirus. diphtheria toxin and tetanus toxin were significantly reduced. In patients, the densit y of the complement-binding receptor CD11b and the Fc-receptor CD16 was sig nificantly enhanced on monocytes and polymorphonuclear neutrophils (PMN) an d the number of phagocytosing PMN was significantly increased in the presen ce of pooled human serum. This was not observed in the presence of autologo us serum, indicating altered opsonic properties. Also in normal PMN, phagoc ytosis was inhibited by a factor in the serum from the patients. Despite ma intained oxidative burst, patient PMN demonstrated insufficient intracellul ar bacterial killing. Conclusion Our data indicate that patients with alpha-mannosidosis have an immunodeficiency at both the humoral and cellular level.