PMID- 10529073
OWN - NLM
STAT- MEDLINE
DCOM- 19991112
LR  - 20131121
IS  - 0268-1315 (Print)
IS  - 0268-1315 (Linking)
VI  - 14
IP  - 5
DP  - 1999 Sep
TI  - Human leukocyte antigen typing, response to neuroleptics, and clozapine-induced 
      agranulocytosis in jewish Israeli schizophrenic patients.
PG  - 305-12
AB  - The atypical antipsychotic agent clozapine is known to be effective in 
      schizophrenic patients refractory to other medications; however, it induces 
      agranulocytosis in approximately 1-2%. In Jews, this complication is associated 
      with the haplotype HLA B38,DR4,DQ3. The aim of the present study was to determine 
      which human leukocyte antigen (HLA) antigens are involved in clozapine-induced 
      agranulocytosis. We performed HLA typing in 88 Jewish Israeli schizophrenic 
      patients and in 127 ethnically matched healthy individuals. Thirty-eight patients 
      responsive to standard antipsychotic medications were treated with haloperidol, 
      and 50 refractory patients received clozapine. A trend was noted for elevated 
      rates of HLA B38 among control individuals and clozapine-treated patients of 
      Ashkenazi origin compared to individuals of non-Ashkenazi origin, but the 
      findings failed to reach statistical significance. No association was found 
      between HLA class I antigens and the response to haloperidol or clozapine. 
      Neutropenia developed in two clozapine-treated patients and agranulocytosis in 
      one. Two of these three patients were of Ashkenazi origin, and both demonstrated 
      the HLA B38 phenotype. Although the findings did not reach a statistical 
      significance because of the small number of patients, they may support an 
      association between clozapine-induced neutropenia/agranulocytosis and Ashkenazi 
      origin and the HLA B38 phenotype. The rate of agranulocytosis in our sample (2%) 
      is similar to the usual cumulative risk of agranulocytosis but in contrast to its 
      high frequency among Jewish American patients. One possible explanation for this 
      difference is the high rate of Ashkenazi patients in the American sample and the 
      preponderance of non-Ashkenazi patients in our population.
FAU - Meged, S
AU  - Meged S
AD  - Abarbanel Mental Health Center, Bat-Yam, Israel.
FAU - Stein, D
AU  - Stein D
FAU - Sitrota, P
AU  - Sitrota P
FAU - Melamed, Y
AU  - Melamed Y
FAU - Elizur, A
AU  - Elizur A
FAU - Shmuelian, I
AU  - Shmuelian I
FAU - Gazit, E
AU  - Gazit E
LA  - eng
PT  - Journal Article
PL  - England
TA  - Int Clin Psychopharmacol
JT  - International clinical psychopharmacology
JID - 8609061
RN  - 0 (Antipsychotic Agents)
RN  - 0 (HLA Antigens)
RN  - J60AR2IKIC (Clozapine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Agranulocytosis/*chemically induced/immunology
MH  - Antipsychotic Agents/*adverse effects/*pharmacology/therapeutic use
MH  - Clozapine/*adverse effects/pharmacology/therapeutic use
MH  - Female
MH  - HLA Antigens/*classification/immunology
MH  - Humans
MH  - Israel
MH  - Jews/*psychology
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Risk Factors
MH  - Schizophrenia/*drug therapy/ethnology
EDAT- 1999/10/21 00:00
MHDA- 1999/10/21 00:01
CRDT- 1999/10/21 00:00
PHST- 1999/10/21 00:00 [pubmed]
PHST- 1999/10/21 00:01 [medline]
PHST- 1999/10/21 00:00 [entrez]
PST - ppublish
SO  - Int Clin Psychopharmacol. 1999 Sep;14(5):305-12.