Summary
The objective of the study was to evaluate the role of autoimmune mechanisms in the pathophysiology of protein S deficiency during HIV-1 infection. In a prospective study the correlation between protein S activity and the presence of anti-protein S autoantibodies or anti-cardiolipin antibodies in HIV-1-positive patients and in a population of patients without HIV infection was investigated. Fifty-five HIV-1-infected patients and 15 hospitalized patients without HIV infection were analysed for protein S activity (functional assay), complement system activation, 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 deviation) 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 group 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 antibodies (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 protein S activity. The exact correlation with plasma levels of these antibodies remains to be investigated.
Zusammenfassung
In der vorliegenden Studie wurden Untersuchungen zur Bedeutung von Autoimmunmechanismen in der Pathophysiologie des Protein-S-Mangels bei HIV-1-Infektion durchgeführt. Die Beziehung zwischen Protein-S-Aktivität und Antikörpern gegen Protein S oder Kardiolipin wurde bei Patienten mit HIV-1-Infektion und ohne HIV-Infektion prospektiv untersucht. In einem funktionalen Assay wurde bei 55 HIV-1-infizierten Patienten und 15 stationären Patienten ohne HIV-Infektion Protein S bestimmt sowie die Aktivierung des Komplementsystems, Vorliegen von Autoantikörpern gegen Protein S (Dot Immunbindung) und IgG-Antikörperspiegel gegen Kardiolipin (ELISA) gemessen. Bei 31/55 HIV-1-positiven Patienten (56,36%) und bei 3/15 (20%) Kontrollpatienten waren Antikörper gegen Protein S nachzuweisen (Fisher's exact test p=0,012). Die Protein-S-Aktivität betrug im Durchschnitt (± Standardabweichung) in der Kontrollgruppe 100,93 (14,73)%, bei HIV-Infizierten 73,70 (20,67)% bei Fällen mit Anti-Protein-S-Antikörpern und 88,08 (25,48)% bei Patienten ohne Anti-Protein-S-Antikörper (Mann-Whitney-U-Test p=0,01). In der HIV-1-positiven Gruppe korrelierte die Protein-S-Aktivität mit zirkulierenden Immunkomplexen (Spearman rank sum test r=− 0,41; p=0,018) und in der Kontrollgruppe mit Anti-Kardiolipin-Antikörpern (Spearman rank sum test r=0,709; p=0,032). Die HIV-Infektion ist folglich mit einer hohen Prävalenz von Antikörpern gegen Protein S und niedriger Protein-S-Aktivität assoziiert. Die genaue Korrelation dieser Antikörper mit Plasmaspiegeln muß noch bestimmt werden.
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Lafeuillade, A., Pellegrino, P., Geoffroy, M. et al. Role of autoimmunity in protein S deficiency during HIV-1 infection. Infection 22, 201–203 (1994). https://doi.org/10.1007/BF01716703
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DOI: https://doi.org/10.1007/BF01716703