Immunological studies in HIV seronegative haemophiliacs: relationships to blood product therapy

Abstract

Immunological studies were performed on a group of 44 haemophilia A and 15 haemophilia B patients who were treated exclusively with blood products manufactured by the Scottish National Blood Transfusion Service (SNBTS). All patients were HIV seronegative throughout the study. Of the haemophilia A patients 14 (32%) had CD4+ lymphocyte subset counts less than or equal to 0.5 x 10(9)/l, compared with one (6%) haemophilia B patient and four (8%) controls. The percentage of activated T cells was greater than 5% in 19/33 (57%) with haemophilia A, 5/9 (55%) haemophilia B and 14/50 (28%) of control subjects. beta 2 microglobulin values greater than or equal to 2.0 mg/l were observed in 19 (43%) haemophilia A and four (26%) haemophilia B patients, compared with one (2%) control. No significant increases in serum interleukin-2 receptor concentrations were observed in 15 haemophilia A and one haemophilia B patients. Significantly elevated levels of IgG, IgM and IgA were observed in the haemophilia A group, but elevation of immunoglobulins was restricted to the IgG class in the haemophilia B group. Of the haemophilia A patients 16/30 (53%) and 6/11 (54%) haemophilia B patients had depression of cell-mediated immunity (CMI) as assessed by delayed-type hypersensitivity responses to intradermally injected recall antigens. There was no correlation between factor VIII or factor IX usage and changes in lymphocyte subsets, beta 2 microglobulin, and immunoglobulin levels. There was, however, a strong correlation between annual factor VIII usage and the degree of depression of CMI for those with haemophilia A but not for those with haemophilia B. No correlation between alterations in the immune parameters and disturbance of liver function tests was observed in either haemophilia A or haemophilia B patients. We conclude that alloantigen or non-HIV viral exposure due to repeated administration of factor concentrates brings about alterations in the immune response, and that these changes are more marked following exposure to intermediate purity factor VIII compared with factor IX concentrate.

Hepatitis C virus quasispecies in the natural course of HCV‐related disease in patients with haemophilia

“…In our cohort four of six patients with progressive liver disease had very high quasispecies homogeneity and we can speculate that the immune damage caused by plasma-derived products, which were in the past overloaded by different foreign proteins, have played a role [26,27]. These findings could reflect a more vigorous and selective immune pressure in these patients, in agreement with the results obtained by Botarelli et al who described an association between the strength of CD4+ T-lymphocyte response to HCV antigens and a more benign course of infection in healthy HCV-seropositive patients.…”

The safety and efficacy of recombinant human blood coagulation factor IX in previously untreated patients with severe or moderately severe hemophilia B

“…Although early plasma-derived FIX (pdFIX) products and prothrombin complex concentrates (PCCs) improved the clinical outcome for patients with hemophilia B, their use was associated with several complications, including thrombosis, disseminated intravascular coagulation, altered immune function, and transmission of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV). [4][5][6] In the past decade, the development of high-purity pdFIX preparations has reduced the thrombogenic risks associated with FIX replacement therapy. [7][8][9] In addition, the introduction of improved viral attenuation methods during manufacture has reduced the risk of viral transmission with pdFIX products.…”

Human recombinant factor IX: safety and efficacy studies in hemophilia B patients previously treated with plasma-derived factor IX concentrates

“…PCCs also contained prothrombin, factor VII, and factor X and their use in hemophilia B was further complicated by thrombosis, generally attributed to the accumulation or delayed clearance of these unactivated and activated vitamin K-dependent proteins. [2][3][4][5] Subsequently, high-purity plasma-derived factor IX concentrates (pdFIX) were developed. These have largely replaced PCCs and have been used successfully for those with a history of thrombosis due to PCCs.…”