The objective of the study was to evaluate the role of autoimmune mech
anisms in the pathophysiology of protein S deficiency during HIV-1 inf
ection. In a prospective study the correlation between protein S activ
ity and the presence of anti-protein S autoantibodies or anti-cardioli
pin antibodies in HIV-1-positive patients and in a population of patie
nts without HIV infection was investigated. Fifty-five HIV-1-infected
patients and 15 hospitalized patients without HIV infection were analy
sed for protein S activity (functional assay), complement system activ
ation, presence of autoantibodies against protein S (Dot Immunobinding
) and levels of anti-cardiolipin IgG antibodies (ELISA). The presence
of anti-protein S antibodies was detected in 31 (56.36%) out of the 55
HIV-1-positive patients and in three (20%) of the 15 control patients
(Fisher's exact test, p = 0.012). The average value (+/- standard dev
iation) of protein S activity was 100.93 (14.73)% in the control group
. For the HIV-1-infected patients it was 73.70 (20.67)% in those with
anti-protein S antibodies compared to 88.08 (25.48)% in those,without
antibodies (Mann-Whitney U Test, p = 0.01). In the HIV-1-positive grou
p protein S activity was correlated with concentrations of circulating
immune complexes (Spearman rank sum test, r = - 0.41, p = 0.018) and
in the control group with concentrations of anti-cardiolipin antibodie
s (Spearman rank sum test, r = 0.709, p = 0.032). In conclusion, HIV-1
infection is associated with a high prevalence of antibodies against
protein S. These antibodies are associated with a significantly low pr
otein S activity. The exact correlation with plasma levels of these an
tibodies remains to be investigated.