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A component of factor VIII preparations which can be separated from factor VIII activity down modulates human
Blood
|April 1, 1987
Summary
Therapeutic factor VIII (F VIII) concentrates can impair monocyte (Mo) immune functions by down-modulating Fc receptors. This effect, caused by contaminants, may increase infection risk in hemophilia patients.
Area of Science:
- Immunology
- Hematology
Background:
- Monocytes (Mo) are crucial immune cells involved in pathogen clearance.
- Factor VIII (F VIII) concentrates are essential for hemophilia treatment.
Purpose of the Study:
- To investigate the effects of therapeutic factor VIII (F VIII) concentrates on monocyte (Mo) functions.
- To identify the component within F VIII concentrates responsible for observed Mo functional changes.
Main Methods:
- Normal monocytes were treated with F VIII concentrates.
- Fc receptor expression and monocyte effector functions (O2 radical release, bacterial killing) were assessed.
- Fractionation techniques (molecular sieving, affinity chromatography) were used to isolate the active component.
Main Results:
- Short-term F VIII concentrate treatment significantly down-modulated Fc receptors on monocytes (P < 0.001).
- F VIII-treated monocytes showed reduced O2 radical release (40% of controls) and bacterial killing capacity (24-51% of controls).
- The modulatory activity was attributed to high-molecular weight contaminants (immune complexes/IgG aggregates), not monomeric IgG.
Conclusions:
- Contaminants in F VIII concentrates can impair monocyte immune functions.
- This impairment may contribute to an immunocompromised state in hemophilia patients.
- Potential for increased opportunistic infections in patients receiving F VIII concentrates.