Relative seroprevalence of human herpes viruses in patients with chronic lymphocytic leukaemia

Abstract

Background: Herpes virus infections may have a significant role in chronic lymphocytic leukaemia (CLL) due to their ability to modulate the host's immune system.

Materials and methods: We examined the seroprevalence of four herpes viruses [Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), human herpes virus (HHV)-6 and -7] in a cohort of European CLL patients (cohort 1, n = 100) in relation to the immunoglobulin variable heavy (IGHV) chain gene use and compared serological results with those obtained from age- and gender-matched healthy adults (n = 100).

Results: CMV-seroprevalence was significantly higher in CLL cohort 1 (79%) than in the control cohort (57%, P = 0.001); the seroprevalence of EBV (89% vs. 94%), HHV-6 (73% vs. 60%), or HHV-7 (35% vs. 35%) was not. In CLL cohort 1, use of IGHV3-30 was more prevalent among CMV-seropositive and of IGHV3-21 among HHV-7-seronegative cases. To investigate the generalizability of these findings, we investigated the herpes virus seroprevalence in a second cohort of age-matched CLL patients from a different geographical area (USA, n = 100, cohort 2). In cohort 2, CMV-seroprevalence was comparable with that of the control cohort (53%). Seroprevalence of EBV, HHV-6 and HHV-7 were 85%, 88% and 73% respectively. In CLL cohort 2, use of IGHV3-30 or IGHV3-21 was not associated with any of the herpes viruses investigated.

Conclusions: CMV-seropositivity is associated with CLL in selected patient cohorts. However, the considerable variation in herpes virus-specific seropositivity between geographically distinct CLL cohorts indicates that seropositivity for any of the four human herpes viruses investigated is not generally associated with CLL.

Figure 1

Relative rates of seropositivity for the four herpes viruses investigated. (a) Comparison of seropositivity between patients of CLL cohort 1 (n = 100) and healthy adults of the control cohort (n = 100); (b) clinical stage of CLL in relation to seropositivity (Rai 0–1, n = 79; Rai 2, n = 14; Rai 3–4, n = 7); (c) samples collected pre-treatment from CLL patients (n = 73) vs. those collected post-treatment (n = 27).

Figure 2

Time between diagnosis of CLL and commencement of therapy in relation to seropositivity for herpes viruses. Kaplan–Meier curves depict the proportion of untreated patients with CLL according to the time since diagnosis. The patients are grouped according to test results for selected herpes virus-specific IgG-antibodies in serum. Patients not treated during follow-up period were included in this analysis as censored cases.

Figure 3

Comparison of IGHV gene use between CLL cohorts 1 and 2. The relative number of CLL IGHV sequences using genes of each IGHV subgroup is shown in the centre donuts, and the distribution of sequences using particular IGHV 1, 3 and 4 genes is depicted peripherally.

Figure 4

Comparison of IGHV gene use between CLL cohorts 1 and 2 with respect to herpes virus-specific seropositivity. (a) Comparison of IGHV subgroups in relation to herpes virus-specific serology. (b) Comparison of the most frequently used IGHV genes in relation to herpes virus-specific serology.

Figure 4

Comparison of IGHV gene use between CLL cohorts 1 and 2 with respect to herpes virus-specific seropositivity. (a) Comparison of IGHV subgroups in relation to herpes virus-specific serology. (b) Comparison of the most frequently used IGHV genes in relation to herpes virus-specific serology.