Neutrophil FcγRIIIb Deficiency, Nature, and Clinical Consequences: A Study of 21 Individuals From 14 Families

• Published in: Blood 1995-09, Vol.86 (6), p.2403-2413
• Main Authors: Haas, Masja de, Kleijer, Marion, Zwieten, Rob van, Roos, Dirk, Borne, Albert E.G.Kr. von dem
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Alleles; Base Sequence; Biological and medical sciences; Blotting, Southern; Disease Susceptibility; Female; Genes; Humans; Immunity, Maternally-Acquired; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infant, Newborn; Infections - etiology; Isoantibodies - immunology; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Neutropenia - congenital; Neutropenia - immunology; Neutrophils - chemistry; Pedigree; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Pregnancy; Receptors, IgG - chemistry; Receptors, IgG - deficiency; Receptors, IgG - genetics; Thyroiditis, Autoimmune - genetics
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V86.6.2403.bloodjournal8662403

Several individuals have been described whose neutrophils lack the normally abundantly expressed IgG Fcγ receptor 1Mb (FcγRIIIb). We now studied the responsible genomic defect and analyzed the medical history in detail of 21 FcγRIIIb-negative donors identified in 14 unrelated families. We developed a polymerase chain reaction allele-specific-primer annealing assay to genotype for the NA polymorphism of the FcγRIIIB gene. All FcγRIIIb-deficient individuals were negative for both the NA1 and the NA2 allele. In all cases the complete absence of the FcγRIIIB alleles was confirmed using a Southern blot-based restriction fragment length polymorphism assay. Furthermore, an additional deletion of the next more telomeric located FcγRIIC gene was found. Family studies showed that at least one FcγRIIIB allele was absent in both parents in 6 families, whereas in 2 families the father had a normal phenotype. Two individuals suffered from an autoimmune thyroiditis. Four individuals had had multiple episodes of infection, 3 had only incidental infections, and 14 never had any serious infection. Genotyping showed a normal FcγRlla phenotype distribution among the FcγRIIIb-negative individuals, thus excluding the possibility that the presence of the favorable lgG2-binding low-responder isoform of FcγRlla (131-H) contributed to the overall absence of recurrent bacterial infections.