Autoantibodies to Leukocyte αMβ2 Integrin Glycoproteins in HIV Infection

HIV infection is often associated with polyclonal B-cell activation, autoantibodies, and clinically evident autoimmune disease. Because neutropenia and anti-neutrophil autoantibodies are common clinical features of HIV disease, we studied a series of HIV+patients to determine whether anti-αMβ2 integrin (MAC-1) specific anti-neutrophil autoantibodies occur in HIV disease, as we have shown to occur in patients with immune neutropenia not associated with HIV. Two new assays specific for anti-αMβ2 IgG were developed to carry out these studies: an ELISA method using affinity-purified αMβ2 integrin protein, and a flow cytometry method using subclones of the 293 human fetal kidney cell line, stably transfected with cDNAs for the αM and/or β2 integrin subunits. In studies of the sera of 20 untreated HIV+individuals, anti-αMβ2 activity was detected in 9 (45%) by one or the other of these assays and in 5 (25%) by both assays. Seven of the 20 HIV+study subjects had unexplained neutropenia, and of these, 6 (86%) were positive for anti-αMβ2 autoantibodies. Our findings indicate that anti-αMβ2 integrin autoantibodies are frequent in HIV+individuals, particularly when unexplained neutropenia is also present, and raise the possibility that these autoantibodies may have a role in the acquired neutrophil dysfunction and increased risk of nonopportunistic bacterial infections observed in HIV disease.