Blood, Vol. 94 No. 5 (September 1), 1999:
pp. 1797-1802
Neutrophil Antibody Specificity in Different Types of
Childhood Autoimmune Neutropenia
Marrie C.A. Bruin,
Albert E.G.Kr von dem Borne,
Rienk Y.J. Tamminga,
Marion Kleijer,
Lica Buddelmeijer, and
Masja de Haas
From the Department of Hematology of the University Hospital for
Children and Youth `The Wilhelmina Childrens Hospital,' Utrecht; CLB,
Sanguin Blood Supply Foundation, and Laboratory for Experimental and
Clinical Immunology, Academic Medical Centre, University of Amsterdam,
Amsterdam; the Department of Hematology, Academic Medical Centre,
University of Amsterdam, Amsterdam; and the Department of Pediatrics,
University Hospital Groningen, Groningen, The Netherlands.
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 µL
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
RIIIb, and CD11a 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-FcRIIIb 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-FcRIIIb antibodies. Thus, characterization of the
antibodies in sera from children with AIN discriminates patients with
primary AIN from those with secondary AIN.
