Autoantibodies to leukocyte alpha M beta 2 integrin glycoproteins in HIV infection

HIV infection is often associated with polyclonal B-cell activation, autoan tibodies, and clinically evident autoimmune disease. Because neutropenia an d anti-neutrophil autoantibodies are common clinical features of HIV diseas e, we studied a series of HIV+ patients to determine whether anti-alpha M b eta 2 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-alpha M beta 2 IgG w ere developed to carry out these studies: an ELISA method using affinity-pu rified alpha M beta 2 integrin protein, and a how cytometry method using su bclones of the 293 human fetal kidney cell line, stably transfected with cD NAs for the alpha M and/or beta 2 integrin subunits. In studies of the sera of 20 untreated HIV+ individuals, anti-alpha M beta 2 activity was detecte d in 9 (45%) by one or the other of these assays and in 5 (25%) by both ass ays. Seven of the 20 HIV+ study subjects had unexplained neutropenia, and o f these, 6 (86%) were positive for anti-alpha M beta 2 autoantibodies. Our findings indicate that anti-alpha M beta 2 integrin autoantibodies are freq uent in HIV+ individuals, particularly when unexplained neutropenia is also present, and raise the possibility that these autoantibodies may have a ro le in the acquired neutrophil dysfunction and increased risk of nonopportun istic bacterial infections observed in HIV disease. (C) 1999 Academic Press .