Key result
Recombinant IFN-alpha 2a is linked to antibody development in ~43% of treated patients.
Why the study?
The geographical distribution of interferon-alpha 2 genes and their relation to antibody development after recombinant interferon-alpha 2a treatment in Japanese patients with chronic viral hepatitis was unclear.
Observational (n=32)
The distinct geographical distribution of IFN-alpha 2 genes suggests that recombinant IFN preparations should match the recipient's genotype to avoid antibody responses.
May support genotype-matched IFN to minimize antibodies; leaves open prospective validation before clinical adoption.
DNA was extracted from leucocytes of 23 Japanese patients with chronic viral hepatitis who received treatment with recombinant interferon-alpha 2a (IFN-alpha 2a) and nine healthy controls, as well as eight human cell lines of Caucasian or African origin. A part of the gene encoding IFN-alpha 2 was amplified by polymerase chain reaction and the sequence of nucleotides 1-231 was determined. Interferon-alpha 2a, -alpha 2b and -alpha 2c genes were tested for in five clones each from a patient or control, or a cell line, based on adenine or guanine at nucleotide positions 68 and 101. The IFN-alpha 2b gene was detected in all 160 clones from 23 Japanese patients and nine controls, but the IFN-alpha 2a or -alpha 2c gene was not found in any. Of five cell lines derived from Caucasians, four exhibited only the IFN-alpha 2b gene, while the remaining one exhibited both IFN-alpha 2a and -alpha 2b genes. Of three cell lines derived from Africans, one each showed only the IFN-alpha 2b or -alpha 2c gene, and the remaining one both IFN-alpha 2b and -alpha 2c genes. The 23 patients with the IFN-alpha 2b gene and chronic viral hepatitis included 10 who developed antibodies against IFN after treatment with recombinant IFN-alpha 2a. These results indicated a distinct geographical distribution of the three IFN-alpha 2 genes, and suggested the use of a recombinant IFN-alpha 2 preparation in agreement with the IFN-alpha 2 gene possessed by the recipient to avoid antibody responses.
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Hosoi et al. (1992) conducted an observational in Chronic viral hepatitis (n=32). IFN-alpha 2 gene type was evaluated on Detection of IFN-alpha 2a, -alpha 2b, and -alpha 2c genes. The IFN-alpha 2b gene was detected in all 23 Japanese patients and 9 controls, with 10 of the 23 patients developing antibodies after treatment with recombinant IFN-alpha 2a.
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