In this study, we analysed the FCGR3A 158 V/F and FCGR2A 131 H/R polymorphisms as possible predictors of response to rituximab therapy in patients with Immune Thrombocytopenic Purpura (ITP) or Autoimmune Hemolytic Anemia (AHA). We analysed 45 ITP patients receiving Rituximab; 18 patients (40%) achieved a maintained response (>100×109 platelets/L, >3 months after the last rituximab dose). The median duration of the response was 19 months (4–76). We also analysed 16 AHA patients treated with rituximab, 12 of whom (75%) achieved a maintained response (Hb increase >1,5 g/dL or Hb >10 g/dL, >3 months after last rituximab dose, with no transfusion). The median duration of response was 8 months (3–48). To analyse the codons 158 of FCGR3A and 131 of FCGR2A we used an original method of PCR with confronting two-pair primers (CTPP). Eight of 45 ITP patients (18%) were homozygous for FCGR3A 158V and 21 (47%) for 158F, while 16 (35%) were heterozygous. The maintained response rates of the three groups were 37%, 33% and 50% respectively, and did not differ significantly. We did not find any significant difference either when comparing FCGR3A 158V homozygotes vs 158F carriers or when comparing 158F homozygotes patients vs 158V carriers. When we analysed FCGR2A, 11 patients (25%) were 131H, 10 (22%) 131R and 24 (53%) were heterozygous. The analysis of the maintained response rate in these three groups (55%, 10% and 46%) showed a tendency to a better response in FCGR2A 131H homo- and heterozygous patients (p = 0.08). When we compared FCGR2A 131H homozygotes vs 131R carriers we found no significant difference. In contrast, the response rate was significantly worse in FCGR2A 131R homozygotes than in 131H carriers (p = 0.028). We did similar analyses in 15 AHA patients, of whom 4 (27%) and 7 (46%) were homozygous for FCGR3A 158V and FCGR3A 158F, respectively, while the remaining 4 were heterozygous (27%). We saw no significant difference in the maintained response rate between the three groups (75%, 86% and 50%). We found no difference either when we compared FCGR3A 158V homozygotes vs. 158F carriers or FCGR3A 158F homozygotes vs. 158V carriers. We determined the FCGR2A 131 H/R state in 16 AHA patients, of whom 3 (19%) and 5 (31%) were homozygous for 131H and 131R, respectively, 8 (50%) being heterozygous. The maintained response rate of the groups (67%, 80% and 75%) did not differ significantly. We found no differences either when comparing FCGR2A 131H homozygotes with 131R carriers or FCGR2A 131R homozygotes with 131H carriers. Our results show no significant influence of the polymorphisms of the gene FCGR3A 158 V/F on the response to rituximab either ITP and AHA patients, unlike previous reports in lymphoma. Polymorphism of FCGR2A 131 H/R could have influence in the response to rituximab therapy in ITP. Absence of 131H allotype is associated with worse response. In AHA patients the studied polymorphisms seem don’t have influence in rituximab response but it necessary to perform larger studies to assess this possible influence.
Disclosure: No relevant conflicts of interest to declare.