An acquired inhibitor to factor VIIIC in a non-hemophiliac: twenty years of observation and characterization.
A non-hemophilic patient with an acquired inhibitor to factor VIIIC was initially diagnosed in this laboratory 20 years ago at age 63. Following its initial appearance in 1963, the inhibitor was detectable on two other occasions. We believe that this is the longest duration such an inhibitor has persisted. No sample remained from his initial admission; however, samples were available from the last 8 years of his life for retrospective study. Preparative isofocusing, affinity chromatography, and immunoglobulin subtyping were used to determine the similarities and/or differences in the inhibitor over these 8 years. The following similarities and differences were observed in both the 1975 and 1983 plasmas. Isofocusing showed that both plasmas contained peaks of inhibitory activity with pIs of 7.25, 8.26, and 8.88; the 1975 sample in addition contained two peaks with pIs of 7.77 and 9.45, whereas two other peaks with pIs of 7.64 and 7.85 were found in the 1983 sample. For the final characterization, each isofocused inhibitory peak was eluted from Protein A Sepharose and incubated with antisera to determine the immunoglobulin subtype. Each peak consisted of mixtures of IgG1 and IgG4 with both kappa and lambda light chains. It was concluded that the inhibitor was polyclonal, based on the presence of inhibitory peaks with different pIs and immunoglobulin subtypes. These findings support the conclusion that the development of and changes in the inhibitor was a dynamic process with some inhibitors (antibodies) persisting, while at the same time others with different characteristics were being formed.
D002846:Chromatography, Affinity / Q000379:methods; D005169:Factor VIII / Q000037:antagonists & inhibitors* / Q000276:immunology; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000097:blood* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007143:Immunoglobulin Heavy Chains / Q000032:analysis; D007147:Immunoglobulin Light Chains / Q000032:analysis; D007525:Isoelectric Focusing; D008297:Male; D008875:Middle Aged
D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D005169:Factor VIII