Assessment Of F9 Genotype Specific Inhibitor Risks Associated With A Large Series Of Argentine Patients With Hemophilia B.

ZIEGLER, BETIANA MICHELLE; MARCHIONE, VANINA DANIELA; WAISMAN, KAREN; ABELLEYRO, MIGUEL MARTÍN; NEME, DANIELA; DE BRASI, CARLOS DANIEL; ROSSETTI, LILIANA CARMEN; RADIC, CLAUDIA PAMELA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2019

Hemophilia B (HB) is an X-linked disorder caused by pathogenic variations in the coagulation factor IX gene (F9). Currently, HB is successfully treated by substitution of the deficient FIX. Development of inhibitory antibodies (INH) against the therapeutic FIX represents a major complication affecting patients and the public health economy. INH development in HB is typically associated with allergic and/or anaphylactic reactions.The objective was to estimate the global and partial F9 genotype risks of INH in a large series of Argentine HB patients (about 1/3 of all HB patients registered in Argentina (WFH Global Survey 2018)).We characterized the HB causative variation in 98 out of 104 studied patients (94% of efficiency) by application of an in-house developed algorithm including 12 PCR-amplifications allowing gross deletion detection in hemizygous probands, small-mutation screening by CSGE (conformation sensitive gel electrophoresis), and Sanger DNA-sequencing of the suspected region. The case(INH+)/control(INH-) study included 10 cases and 94 controls (n=104) assessing a global absolute INH-prevalence (GAIP) of 9.6%.Absolute and relative risks of each F9-genotype are presented as INH-prevalence, AIP and odds ratios, OR(CI95%), respectively. Large F9-deletions showed increased risks, AIP of 50% (6/12) and an OR of 22(4.8-99.7) p=0.0001; and considering entire F9-deletions, an AIP of 71% (5/7) and OR of 46(7.1-298) p