Griffiths Kira, Mellado Maria Ruiz, Chung Raymond, Lally John, McQueen Grant, Sendt Kyra-Verena, Gillespie Amy, Ibrahim Muhammad, Richter Alex, Shields Adrian, Ponsford Mark, Jolles Stephen, Hodsoll John, Pollak Thomas A, Upthegrove Rachel, Egerton Alice, MacCabe James H
Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK.
Department of Social Genetic and Developmental Psychiatry, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK.
Brain Behav Immun. 2024 Jan;115:223-228. doi: 10.1016/j.bbi.2023.10.001. Epub 2023 Oct 11.
Use of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored.
This prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS).
IgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: β = -32.66, 95% CI = -62.38, -2.93, p = 0.03; IgG: β = -63.96, 95% CI = -118.00, -9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: β = -23.48, 95% CI = -39.56, -7.42, p = 0.004; 24 weeks: β = -33.12, 95 %CI = -50.30, -15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03).
The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.
由于存在不良反应风险，氯氮平在难治性精神分裂症治疗中的应用常受到限制。已有报道称氯氮平治疗与低免疫球蛋白水平之间存在横断面关联，然而需要前瞻性研究来确定时间关系。我们检验了以下假设：在氯氮平治疗开始后的前6个月内，免疫球蛋白水平会降低。同时还探讨了氯氮平治疗过程中免疫球蛋白水平与症状严重程度之间的关系。
这项前瞻性观察性研究测量了56例难治性精神分裂症患者在开始使用氯氮平后的6周、12周和24周时的免疫球蛋白（Ig）水平（A、M和G）。在12周时还使用阳性和阴性症状量表（PANSS）测量了临床症状。
氯氮平治疗期间，IgA、IgG和IgM均下降。对于IgA和IgG，在24周时下降显著（IgA：β=-32.66，95%CI=-62.38，-2.93，p=0.03；IgG：β=-63.96，95%CI=-118.00，-9.31，p=0.02）。对于IgM，在12周和24周时下降显著（12周：β=-23.48，95%CI=-39.56，-7.42，p=0.004；24周：β=-33.12，95%CI=-50.30，-15.94，p=<0.001）。氯氮平治疗期间IgA和IgG的下降与12周内PANSS总分的下降相关（n=32，IgA r=0.59，p=0.005；IgG r=0.48，p=0.03）。
在氯氮平治疗的6个月内观察到免疫球蛋白水平下降，这进一步证明了氯氮平与继发性抗体缺乏之间的联系。然而，Ig降低与症状改善之间的关联可能表明免疫机制对氯氮平的有益和不良影响均有作用。
