MedicalResearch.com Interview with:
Jun-ichi Nishimura, M.D., Ph.D.
Assistant Professor Department of Hematology and Oncology
Osaka University Graduate School of Medicine
C9, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
MedicalResearch.com: What are the main findings of the study?
Dr. Nishimura: Our major findings are a C5 mutation (c.2654G→A) in Japanese patients with PNH prevents binding and blockade by eculizumab, a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement–mediated hemolysis associated with PNH, while retaining the functional capacity of the mutant C5 to cause hemolysis.
MedicalResearch.com: Were any of the findings unexpected?
Dr. Nishimura: Yes, one patient with a poor response to eculizumab was referred to us from Argentina. Although the known C5 polymorphism (c.2654G→A) was not identified in this patient, a new mutation (c.2653C→T) was detected in the base next to the known polymorphism, suggesting the importance of this site in C5 recognition by eculizumab.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Nishimura: Today’s take home messages are that the polymorphism in the target protein might be important to consider in patients with a poor response to the antibody-based treatments for various diseases.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Nishimura: We will need to verify the distribution of these variants, especially among Asian, South American, Middle Eastern, and African countries.
Genetic Variants in C5 and Poor Response to Eculizumab
Jun-ichi Nishimura, M.D., Ph.D., Masaki Yamamoto, M.D., Shin Hayashi, M.D., Ph.D., Kazuma Ohyashiki, M.D., Ph.D., Kiyoshi Ando, M.D., Ph.D., Andres L. Brodsky, M.D., Ph.D., Hideyoshi Noji, M.D., Kunio Kitamura, M.D., Ph.D., Tetsuya Eto, M.D., Toru Takahashi, M.D., Masayoshi Masuko, M.D., Ph.D., Takuro Matsumoto, M.D., Yuji Wano, M.D., Tsutomu Shichishima, M.D., Ph.D., Hirohiko Shibayama, M.D., Ph.D., Masakazu Hase, Ph.D., Lan Li, M.D., Krista Johnson, M.Sc., Alberto Lazarowski, Ph.D., Paul Tamburini, Ph.D., Johji Inazawa, M.D., Ph.D., Taroh Kinoshita, Ph.D., and Yuzuru Kanakura, M.D., Ph.D.
N Engl J Med 2014; 370:632-639
February 13, 2014DOI: 10.1056/NEJMoa1311084