Contributions
Abstract: PB2113
Type: Publication Only
Background
Chronic primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by enhanced clearance of platelets and impaired platelet production. Corticosteroid is the ministry line of treatment of ITP, patients who fail to respond to steroid (steroid resistant) or who relapse (steroid dependant) face the options of treatment with second line including anti CD-20 monoclonal antibody rituximab. Rituximab is a chimeric IgG1 monoclonal antibody (mAbs). The major mechanism of action of rituximab is the antibody-dependent cellular cytotoxicity (ADCC), ADCC effectiveness is influenced by process of activation of effector cells via their immunoglobulin G fragment C receptors (FcγRs). Fcγ receptors show distinct affinity to bind to IgG subtype specificities. Differential response to rituximab has been reported to correlate with specific polymorphisms in two of FcγR genes: FcγRIIa (H131R) and FcγRIIIa (V158F) in some diseases.
Aims
To clarify the effect of FcγRIIa-131 R/H and FcγRIIIa-158 V/F genes polymorphism on the response to rituximab in ITP patients.
Methods
We studied the frequency of the FCγRIIa (H131R) and FcγRIIIa (V158F) gene polymorphisms, in 100 chronic ITP patients; divided into 2 equal groups, first group received rituximb (375 mg /m2 per dose weekly for four weeks) and the other group received non-mabthera second line therapy. A polymerase chain reaction-restriction fragment length polymorphism assay [PCR-RFLP] was used to detect FcγRIIa-131 R/H and FcγRIIIa-158 V/F genes polymorphism. Evaluation of platelets counts was assessed initially before starting second line therapy then weekly for 3 months. At the end of third month the response to second line therapy was considered according to the following criteria; complete response (CR) PLT > 100 × 109/L., partial Response (R), PLT =30- 100 × 109/L, no response (NR), PLT< 30 × 109/L.
Results
Regarding FcγRIIa gene (H131R) polymorphism distribution in the 100 patients; 28 patients (28%) had wild HH genotype, 41 patients (41%) have heterozygous genotype (HR) and 31patients (31%) have homozygous mutant genotype (RR). In our study, the 100 ITP patients included showed wild type of FcγRIIIa (V158F) gene polymorphism. By the end of month 3 of the second line therapy, 43/100 patients (43%) achieved CR, 37/100 patients (37%) achieved PR and 20/100 patients (20%) achieved NR.
Conclusion
The higher platelet count achieved early (end of week 1, 2, and 3) after rituximab is suggestive for a better response later (at end of M3). FcγRIIa RR genotype is predictive for better response to rituximab in ITP patients
Session topic: 32. Platelets disorders
Keyword(s): Fc receptor, Rituximab, ITP, Gene polymorphism
Abstract: PB2113
Type: Publication Only
Background
Chronic primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by enhanced clearance of platelets and impaired platelet production. Corticosteroid is the ministry line of treatment of ITP, patients who fail to respond to steroid (steroid resistant) or who relapse (steroid dependant) face the options of treatment with second line including anti CD-20 monoclonal antibody rituximab. Rituximab is a chimeric IgG1 monoclonal antibody (mAbs). The major mechanism of action of rituximab is the antibody-dependent cellular cytotoxicity (ADCC), ADCC effectiveness is influenced by process of activation of effector cells via their immunoglobulin G fragment C receptors (FcγRs). Fcγ receptors show distinct affinity to bind to IgG subtype specificities. Differential response to rituximab has been reported to correlate with specific polymorphisms in two of FcγR genes: FcγRIIa (H131R) and FcγRIIIa (V158F) in some diseases.
Aims
To clarify the effect of FcγRIIa-131 R/H and FcγRIIIa-158 V/F genes polymorphism on the response to rituximab in ITP patients.
Methods
We studied the frequency of the FCγRIIa (H131R) and FcγRIIIa (V158F) gene polymorphisms, in 100 chronic ITP patients; divided into 2 equal groups, first group received rituximb (375 mg /m2 per dose weekly for four weeks) and the other group received non-mabthera second line therapy. A polymerase chain reaction-restriction fragment length polymorphism assay [PCR-RFLP] was used to detect FcγRIIa-131 R/H and FcγRIIIa-158 V/F genes polymorphism. Evaluation of platelets counts was assessed initially before starting second line therapy then weekly for 3 months. At the end of third month the response to second line therapy was considered according to the following criteria; complete response (CR) PLT > 100 × 109/L., partial Response (R), PLT =30- 100 × 109/L, no response (NR), PLT< 30 × 109/L.
Results
Regarding FcγRIIa gene (H131R) polymorphism distribution in the 100 patients; 28 patients (28%) had wild HH genotype, 41 patients (41%) have heterozygous genotype (HR) and 31patients (31%) have homozygous mutant genotype (RR). In our study, the 100 ITP patients included showed wild type of FcγRIIIa (V158F) gene polymorphism. By the end of month 3 of the second line therapy, 43/100 patients (43%) achieved CR, 37/100 patients (37%) achieved PR and 20/100 patients (20%) achieved NR.
Conclusion
The higher platelet count achieved early (end of week 1, 2, and 3) after rituximab is suggestive for a better response later (at end of M3). FcγRIIa RR genotype is predictive for better response to rituximab in ITP patients
Session topic: 32. Platelets disorders
Keyword(s): Fc receptor, Rituximab, ITP, Gene polymorphism