Tom Howard, Marcio Almieda, Vincent Diego, Kevin Viel, Bernadette Luu, Karin Haack, Rajalingam Raja, Afshin Ameri, Meera Chitlur, Natalia Rydz, David Lillicrap, Raymond Watts, Craig Kessler, Christopher Ramsey, Long Dinh, Benjamin Kim, Jerry Powell, Juan Peralta, Ruayda Bouls, Shirley Abraham, Yu-Min Shen, Carlos Murillo, Henry Mead, Paul Lehmann, Eli Fine, Miguel Escobar, Satish Kumar, Sarah Williams-Blangero, Carol Kasper, Laura Almasy, Shelley Cole, John Blangero, Barbara Konkle
Hemophilia-A (HA) is caused by heterogeneous loss-of-function factor (F)VIII gene ( F8 )-mutations and deficiencies in plasma-FVIII-activity that impair intrinsic-pathway-mediated coagulation-amplification. The standard-of-care for severe-HA-patients is regular infusions of therapeutic-FVIII-proteins (tFVIIIs) but ~30% develop neutralizing-tFVIII-antibodies called "FVIII-inhibitors (FEIs)" and become refractory. We used the PATH study and ImmunoChip to scan immune-mediated-disease (IMD)-genes for novel and/or replicated genomic-sequence-variations associated with baseline-FEI-status while accounting for non-independence of data due to genetic-relatedness and F8 -mutational-heterogeneity...
October 18, 2023: Research Square