Neutrophil antibody specificity in different types of childhood autoimmune neutropenia

Autoimmune neutropenia (AIN) in children can be divided into 2 forms. In primary AIN, neutropenia is the sole abnormality, and although neutrophil counts are generally below 500 mu L-1, mild bacterial infections occur. Primary AIN is mostly seen in young children and shows a self-limited course. AIN occurring in association with autoimmune diseases (secondary AIN) often shows more severe infectious complications. We analyzed clinical and serological data from 28 pediatric patients with AIN to evaluate whether there is a possible relationship between specificity of the neutrophil autoantibodies and the clinical course of the disease. Specificity of the circulating antibodies was determined with the indirect granulocyte immunofluorescence test (GIFT) and a panel of phenotyped donor neutrophils. The samples were further analyzed in the monoclonal antibody immobilization of granulocyte antigens assay (MAIGA) for neutrophil antigen (NA)1, NA2, CD11a, and CD11b specificity. With the indirect GIFT, an antibody specificity was deduced in 26 of the 28 analyzed samples. In all but 3 sera from patients with primary AIN, NA1-(76%) or NA2-(10%) specific antibodies were detected with the indirect GIFT. In 2 samples, the reactivity in the indirect GIFT was too weak to draw conclusions, but the MAIGA showed NA1 and/or NA2 specificity of the antibodies. One serum, from a patient with primary AIN with a persistent neutropenia for more than 6 years, contained NA1, possibly pan-Fc gamma RIIIb, and CDIIa antibodies. In 4 sera from patients with primary AIN, weak antibodies with CD11a or CD11b specificity were detected with the MAIGA. Sera from 7 patients with secondary AIN contained in all cases antibodies with pan-Fc gamma RIIIb specificity, as deduced from the indirect GIFT results and absorbance/ elution experiments performed with 2 sera. The MAIGA confirmed this for only 1 of the 5 tested sera, Furthermore, CD11a antibodies were detected in 1 of the 5 tested sera. In conclusion, our results indicate that primary AIN is usually associated with NA-specific antibodies, whereas secondary AIN seems to be associated with pan-Fc gamma RIIIb antibodies. Thus, characterization of the antibodies in sera from children with AIN discriminates patients with primary AIN from those with secondary AIN. (C) 1999 by The American Society of Hematology

The Fc gamma RIIIA-158F allele is a risk factor for systemic lupus erythematosus

Objective. To study whether the Fc gamma RIIIA-158V/F polymorphism, which affects IgG binding affinity, is a risk factor for systemic lupus erythematosus (SLE), Methods. We genotyped a group of 70 Caucasian SLE patients for all known Fc gamma R polymorphisms. Of this group, 45 patients (64%) had nephritis, In 35 patients, this diagnosis was confirmed by renal biopsy, Results, In the total group of 70 SLE patients, the frequency of the Fc gamma RIIIA-158F allele was 0.74, versus 0.57 in healthy controls (P = 0.003), The genotype distribution of the Fc gamma RIIIA-158V/F polymorphism was also significantly different from that of the control population (P = 0.004). The distribution of the other Fc gamma R polymorphisms-Fc gamma RIIA-131R/H, Fc gamma RIIIB-NA(1/2), and Fc gamma RIIIA-48L/R/H-was similar in SLE patients and controls, Conclusion. In our group of SLE patients, only the distribution of the alleles of the Fc gamma RIII4-158V/F polymorphism nas significantly different from that in the control group. This might indicate that macrophage expression of the Fc gamma RIIIA-158F isoform is involved in the disturbed clearance of immune complexes in patients with SLE