Successful re-treatment of an anti-interferon resistant polycythaemia vera patient with lymphoblastoid interferon-alpha N1 and in vitro studies on the specificity of the antibodies.
A polycythaemia vera patient who initially responded to recombinant IFN-alpha 2 (rIFN-alpha 2) treatment developed neutralizing antibodies (NA) against it and lost response. Despite raising the dose, clinical resistance persisted and NA increased when two alternative rIFN-alpha 2 preparations were used. When treatment was switched to lymphoblastoid IFN-alpha (lyIFN-alpha N1), clinical response was restored and maintained. During re-treatment, NA specific for the earlier rIFN-alpha 2 preparations redeveloped and cross-reacted extensively with each other but not with 'whole' lyIFN-alpha N1 and only minimally with the lyIFN-alpha 2 subtype within it. These findings demonstrate the relevance of NA specificities in the re-treatment of antibody-compromised patients.
Wellcome Research Laboratories, Beckenham, Kent, U.K.
C M
CM
Brand
L
L
Leadbeater
R
R
Budiman
K
K
Lechner
H
H
Gisslinger
D000906:Antibodies / Q000097:blood; D000918:Antibody Specificity; D003429:Cross Reactions; D004351:Drug Resistance / Q000276:immunology; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000627:therapeutic use; D016898:Interferon-alpha / Q000276:immunology / Q000627:therapeutic use*; D008875:Middle Aged; D011087:Polycythemia Vera / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins
D000906:Antibodies; D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins