Association between Hlaantigens and Progression of HIV Infection in Greek Haemophiliacs

Abstract

SUMMARYThe frequencies of HLA antigens in 33 HIV seronegative and in 88 HIV seropositive haemophiliacs, who have been followed for at least 6 years since seroconversion or first HIV positive test. were evaluated in relation to disease susceptibility and disease progression. A high frequency of HLA-A2 and -DR2 antigens and a low frequency of HLA-A9 were found to characterize HIV seropositive patients (p<0.05). Progressors to symptomatic CDC stage IV had a higher frequency of HLA-A9 (p<O.O I) and DR3 . Rapid decline of CD4+ T cells in these patients was associated with HLA-A9, -DR I and DR3. Our data suggest that HLA antigens may contribute to susceptibility to HIV infection and disease progression in Greek haemophiliacs. KEY WORDSHLA antigens Haemophilia CD4+ T lymphocytes CDC staging INTRODUCTION HLA molecules play an important role in the susceptibility and progression of certain autoimmune and infectious diseases . Several published studies provide evidence that various MHC factors may be associated with susceptibility or resistance to HI V infection and progression to AIDS (Pollack et al., 1983; Raffoux et aI. , 1987; Mann et aI., 1988;Steel et al. , 1988; Jeannet et al., 1989; Fabio et ai" 1990;Moreno et al., 1991 and Cameron et aI., 1991). However, the reported HLA associations are conflicting. This may be due to heterogeneity in the genetic background and mode of HIV transmission in the groups studied as well as in the duration of HI V infection. Cohorts ofhaemophiliacs are particularly suitable for such a study because of the close medical follow up of this group of patients and the known date of seroconversion in most cases,In a previous study of 60 unrelated Greek haemophi Jiacs, we were unable to detect any association between HLA-A , B and DR antigens and susceptibility or resistance to HIV infection (Papasteriades et ai" 1986). Having now data on a larger group of patients who are known to be HIV infected for more than six years, we have further extended the study investigating whether the HLA antigens are a predisposing factor for the development of AIDS.Requests for reprints to: Dr. Chr. Papasteriades,

HLA antigens as predictors of disease progression in HIV‐infected haemophilia patients (a 22 years’ follow up)

“…Associations of slow progressors with alleles such as HLA‐B18 and B27 that have been frequently reported [22,23,25] have not been found in this study. On the other hand we find of interest the fact that this study is in agreement with other studies reporting the significant association of HLA‐DR3 (single or in combination with other HLA alleles) with fast progression of HIV infection, rapid decline of CD4+ T cells, or evolution to AIDS and death [7–11,23,25] and confirms our previous reported findings [12]. In this study we have not been able to confirm the association with the haplotypes HLA‐B8 and DR3 or HLA‐A1, B8 and DR3, as we have not proceeded to family studies.…”

“…This kind of controversy in HLA antigen associations with parameters of HIV infection has been observed for other HLA antigens as well. The reason we have not been able to confirm the association of HLA‐A24 (A9) with rapid HIV disease progression reported in our previous study [12] in the same cohort of haemophilics may be due to the fact that in the previous CDC staging system we had used [27] category IV contained both symptomatic cases without AIDS (IVC‐2), which is related to stage B in the 1993 HIV revised classification system and cases with full blown AIDS (IVC‐1) [28]. Moreover the longer follow up of the present study discriminated better rapid and slow progressors.…”

“…In 1993 we published the results of a study on HLA associations and progress of HIV infection in Greek haemophilics followed up for 6–10 years [12]. The results showed that patients who progressed to CDC stage IV in comparison to those who remained asymptomatic in stages II and III had a higher frequency of HLA‐A9 ( P < 0.01) and HLA‐DR3.…”

Frequency of HLA class 1 and 2 alleles in Brazilian patients with AIDS and cytomegalovirus retinitis

“…In addition, the aetiological fraction indicates that the contribution to the development of AIDS conferred by the presence of HLA‐A31 would be 11.05%. Thus, the presence of HLA‐A31 antigen may be considered a risk factor for developing AIDS, suggesting that the HLA system plays a role in the development of AIDS in Brazilian patients, as previously reported by other authors (Itescu et al 1992; Pappasteriades et al 1993; Just et al 1995; Achord et al 1996; Carrington et al 1999; Michael 1999).…”

“…Immunogenetic susceptibility to infectious diseases is an issue that has not been completely understood, and disease association with major histocompatibility complex (MHC) alleles may vary according to the study population. Major histocompatibility complex class 1, 2 and 3 alleles, MHC haplotype and tumour necrosis factor‐β (ΤΝF‐β) gene polymorphism have been reported in association with AIDS or progression to AIDS in many populations of distinct ethnic backgrounds (Pappasteriades et al 1993). Although several studies have evaluated the association of HLA alleles and AIDS, few studies have focused on the association between AIDS and CMV‐R.…”