Markers biologici di risposta clinica alla clozapina in soggetti schizofrenici resistenti al trattamento : il ruolo degli antigeni del sistema HLA

It has been suggested that the individual susceptibility to develop agranulocytosis and the patients' responsiveness to clozapine are both Human Leukocyte Antigen (HLA) associated. The study below was designed to re-examine the role of HLA antigens in influencing the clinical outcome of clozapine treatment in schizophrenic patients refractory to treatment. 112 Italian schizophrenic outpatients were treated with clozapine for 8 months. BPRS was used to assess clinical symptomatology at baseline (T0) and after 8 months' clozapine therapy (T1). HLA were serologically typed on peripheral blood lymphocytes at T1. None of the patients developed agranulocytosis or leucopenia. 23 patients (20.53%) were rated as high clozapine responders (as defined by a BPRS score reduced by =60% from T0 to T1) and 46 patients (41.06%) as low clozapine responders (as defined by a BPRS score reduced by <40% from T0 to T1). Looking at the frequencies of HLA antigens between high and low clozapine responders, our results show that HLA B35 seems to be a strong predictor of a high response to the drug (high responders vs low clozapine responders OR = 3.65, p = 0.042). Our results suggest that HLA-B35 antigen behaves like strong and independent predictor of clozapine responsiveness in Italian schizophrenic patients refractory to treatment.