Aziri Helena, Vallianatou Kalliopi, Balgobin Bhirundra, Taylor David
Institute of Pharmaceutical Sciences, King's College London, UK.
Institute of Pharmaceutical Sciences, King's College London, UK; and Pharmacy Department, South London and Maudsley NHS Foundation Trust, London, UK.
Br J Psychiatry. 2025 Aug;227(2):533-537. doi: 10.1192/bjp.2024.236.
Clozapine therapy presents a risk of agranulocytosis, necessitating monitoring of white blood cell count. The detection of benign ethnic neutropenia (BEN), in which neutropenia can be present without an increased risk of infection, is particularly important in preventing unnecessary withdrawal of clozapine. BEN is strongly linked to the CC homozygote of the single nucleotide polymorphism rs2814778 in the atypical chemokine receptor-1 () gene.
We introduced voluntary genetic testing for BEN in one of our clozapine clinics, with the aim of assessing the prevalence of undiagnosed BEN in patients on clozapine.
We offered genetic testing for BEN to patients undergoing medium- and long-term clozapine treatment, and conducted a comparative analysis of neutrophil counts across three identified groups: those previously diagnosed with BEN, those with newly discovered BEN and those confirmed by genetic testing not to have BEN.
We conducted genetic testing for BEN on 108 patients. Of these, 16 were already registered as having BEN and had the CC homozygote. A further 26 patients (24% of the cohort) who were previously not diagnosed with BEN by standard haematological monitoring were found to have the CC homozygote on genetic testing. Unadjusted mean neutrophil counts were lowest for those with previously diagnosed BEN (2.5 × 10/L, 95% CI 2.2-2.8; < 0.001 other groups), but those with newly discovered BEN had mean counts that were significantly lower (4.1 × 10/L, 95% CI 3.6-4.7) than those with TT and CT genotypes (5.1 × 10/L, 95% CI 4.7-5.4; = 0.006).
Undiagnosed BEN was common in our naturalistic cohort. The integration of genetic testing into standard monitoring would enhance the management of clozapine therapy, potentially allowing for the safe reintroduction or continuation of clozapine in patients with hitherto unrecognised BEN. All current and prospective clozapine patients should be genetically tested for BEN.
氯氮平治疗存在粒细胞缺乏症风险，因此需要监测白细胞计数。良性种族性中性粒细胞减少症（BEN）的检测尤为重要，在该病症中，中性粒细胞减少症可能存在但感染风险并未增加，这对于防止不必要地停用氯氮平至关重要。BEN与非典型趋化因子受体-1（）基因中单个核苷酸多态性rs2814778的CC纯合子密切相关。
我们在我们的一家氯氮平诊所引入了针对BEN的自愿基因检测，目的是评估氯氮平治疗患者中未诊断出的BEN的患病率。
我们为接受中长期氯氮平治疗的患者提供BEN基因检测，并对三个已确定的组的中性粒细胞计数进行了比较分析：那些先前被诊断为BEN的患者、那些新发现BEN的患者以及经基因检测确认没有BEN的患者。
我们对108名患者进行了BEN基因检测。其中，16人已登记患有BEN且具有CC纯合子。另外26名患者（占队列的24%），他们之前通过标准血液学监测未被诊断出患有BEN，但基因检测发现他们具有CC纯合子。先前诊断为BEN的患者未调整的平均中性粒细胞计数最低（2.5×10/L，95%可信区间2.2 - 2.8；与其他组相比，<0.001），但新发现BEN的患者的平均计数显著低于TT和CT基因型的患者（4.1×10/L，95%可信区间3.6 - 4.7）（5.1×10/L，95%可信区间4.7 - 5.4；=0.006）。
在我们的自然队列中，未诊断出的BEN很常见。将基因检测纳入标准监测将加强氯氮平治疗的管理，有可能使迄今未被识别出患有BEN的患者安全地重新使用或继续使用氯氮平。所有目前和未来的氯氮平患者都应进行BEN基因检测。
