我が国のHIV-1感染血友病患者におけるHIV-1 V3領域型特異的抗体に関する研究 : その同定ならびに抗体力価と臨床像との関連

Abstract

The V3-domain within gp120 of HIV-1 elicits virus neutralizing antibodies (Ab). In North American-European strains of HIV-1, the GPGR-motif of V3-loop is conserved, whereas in African strains this motif is substituted by GP (or L) GQ. Therefore, a linear amino acid sequence including these motifs is called the principal neutralizing determinant (PND). However, the correlation between clinical stage of HIV-1-infected individuals and anti-PND Ab titers has not yet been well investigated. In this paper, I established that a high frequency (44%) of anti-PND Ab against HIV-1 мɴ strain was observed in 93 seropositive Japanese hemophiliacs using a panel of PND-peptides and an enzyme-linked immunosorbent assay. The cDNA sequence analysis of V3-domain of HIV-1 isolated from patient sera also revealed that the high-responder against PNDмɴ-peptide well conserved the original sequence. Further, based on the determination of anti-PNDмɴ Ab (MN- Ab) titer during the past 10 years, 35 HIV-1-infected Japanese hemophiliacs with a well-characterized natural history were categorized. Group 1 : MN-Ab was consistently negative (<20). Group 2 : MN-Ab titer was within 20-100. Group 3 : MN-Ab titer was initially high, but decreased later. Group 4 : MN-Ab titer was kept high (>100). Patients of group 1 were further divided into two subgroups based on CD4-positive cell count ; namely, subgroup 1a and subgroup 1b. Without exception, the patients belonging to groups 1a, 2, and 3 showed a consistent decrease in CD-4 positive cell counts and a progression to HIV-l-induced disease. Virus isolation test was frequently positive (65-69.4%). In contrast, the patients of group 4 remained asymptomatic carriers. Virus isolation was also less frequent (16.0%). In addition, a marked increase in serum IgA levels was found in many patients of groups 1a, 2, and 3, but this was not seen in any patients of group 4. These results indicate that a high level of anti-PNDмɴ Ab titer in sera well reflects retardation of the disease progression.