Identification of autoantibodies specific for the neutrophil adhesion
glycoproteins CD11b/CD18 in patients with autoimmune neutropenia
KR Hartman and DG Wright
Department of Hematology, Walter Reed Army Institute of Research,
Washington, DC 20307-5100.
Anti-neutrophil antibodies have been described in a variety of clinical
conditions associated with neutropenia. However, relatively little is known
about the antigenic specificities of naturally occurring anti- neutrophil
autoantibodies. We investigated the possibility that anti- neutrophil
antibodies specific for the neutrophil adhesion glycoprotein (GP) complex
CD11b/CD18 might be present in the sera of some patients with autoimmune
neutropenia. These membrane GPs have been shown to be highly immunogenic in
the production of murine monoclonal antibodies against neutrophil antigens.
Moreover, autoantibodies to the platelet membrane GP complex IIb/IIIa,
another member of the integrin family of cell adhesion proteins, have been
demonstrated in immune thrombocytopenic purpura. Sera from 50 patients
known to have anti- neutrophil IgG antibodies were evaluated using an
immunobead "antigen capture" assay, modeled after a method used to identify
anti-platelet GPIIb/IIIa autoantibodies. This assay detected
anti-CD11b/CD18 autoantibodies in seven of the 50 sera. Each of these seven
sera demonstrated decreased IgG binding to the neutrophils of a patient
with congenital deficiency of CD11b/CD18. The patient with the highest
levels of anti-CD11b/CD18 suffered recurrent skin infections and
cellulitis, and died of respiratory failure during one of multiple episodes
of pneumonia. Purified IgGs from five of these patients demonstrated
effects on adhesion and/or opsonin receptor-mediated functions when tested
with intact neutrophils in vitro. Our findings indicate that some patients
with autoimmune neutropenia have autoantibodies specific for the
functionally important neutrophil adhesion proteins CD11b/CD18. Our
findings also raise the possibility that these autoantibodies may, in some
cases, interfere with neutrophil function, thereby amplifying the risk of
infection associated with neutropenia.
Volume 78,
Issue 4,
pp. 1096-1104,
08/15/1991
Copyright © 1991 by The American Society of Hematology
