Evans, Jennifer Anne; (2001) Blood borne virus infection and immune modulation in boys with haemophilia A. Doctoral thesis (M.D), UCL (University College London).

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Abstract

A major complication of the treatment of haemophilia with factor concentrates was the transmission of viral infections particularly, hepatitis B, HIV and non-A non-B hepatitis (NANBH). There was also evidence of immune dysfunction occurring even in the absence of HIV infection and it remained unclear, whether this was due to other repeated viral infections or to the concentrates themselves. The first aim of this study was to ascertain the safety of an intermediate purity factor VIII concentrate, BPL 8Y, which was dry heated at 80 C for 72 hours. Twenty five previously untreated patients, followed for up to eleven years have shown no evidence of infection with HIV, hepatitis B or NANBH. As it became apparent that this group of boys was remaining free of significant viral infections it provided an opportunity to follow the group prospectively as regards immune function. To determine firstly, whether the previously described immune abnormalities occurred in a virus free population and secondly, if they did occur what was the relation of the immune dysfunction to concentrate treatment. IgG levels remained stable over eleven years and no consistent changes in CD4 or CD8 levels were seen in twenty one of the patients followed over ten years. Lymphocyte proliferation to mitogens and monocyte function were compared with a control group, and with two other groups of haemophiliacs, one HIV seropositive and a second group who, although remaining HIV seronegative had become infected with hepatitis viruses. The responses of the BPL 8Y haemophiliacs were comparable to those of controls and better than those of the other haemophiliacs. However, looking at the data closely the responses at sub-optimal concentrations of mitogens were lower than those of controls although this was not statistically significant. A similar picture was also seen in the monocyte function assay. In conclusion, these patients, remaining free of significant viral infections are not demonstrating dramatic changes in immune function, but, at the same time they are not entirely normal. These subtle changes imply that patients must continue to be studied and that there is no room for complacency.

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