Article Text

Clinical and laboratory characteristics of clozapine-treated patients with schizophrenia referred to a national immunodeficiency clinic reveals a B-cell signature resembling common variable immunodeficiency (CVID)
  1. Mark James Ponsford1,2,
  2. Rachael Steven1,
  3. Kathyrn Bramhall1,
  4. Mathew Burgess1,
  5. Sonali Wijetilleka1,
  6. Emily Carne1,
  7. Frances McGuire1,
  8. Colin R Price1,
  9. Mo Moody1,
  10. Soha Zouwail3,4,
  11. Tayyeb Tahir5,
  12. Daniel Farewell6,
  13. Tariq El-Shanawany1,
  14. Stephen R A Jolles1
  1. 1 Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
  2. 2 Tenovus Institute, Division of Infection & Immunity, Cardiff University, Cardiff, UK
  3. 3 Department of Medical Biochemistry, University Hospital of Wales, Cardiff, UK
  4. 4 Department of Medical Biochemistry, Medical School, Alexandria University, Alexandria, Egypt
  5. 5 Liaison Psychiatry, University Hospital of Wales, Cardiff, UK
  6. 6 Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, UK
  1. Correspondence to Dr Mark James Ponsford, Immunodeficiency Centre for Wales, UHW, Cardiff CF14 4XW, UK; ponsfordm{at}


Aims An association between antibody deficiency and clozapine use in individuals with schizophrenia has recently been reported. We hypothesised that if clozapine-associated hypogammaglobulinaemia was clinically relevant this would manifest in referral patterns.

Methods Retrospective case note review of patients referred and assessed by Immunology Centre for Wales (ICW) between January 2005 and July 2018 with extraction of clinical and immunological features for individuals with diagnosis of schizophrenia-like illness.

Results 1791 adult patients were assessed at ICW during this period; 23 patients had a psychiatric diagnosis of schizophrenia or schizoaffective disorder. Principal indications for referral were findings of low calculated globulin and immunoglobulins. Clozapine was the single most commonly prescribed antipsychotic (17/23), disproportionately increased relative to reported use in the general schizophrenia population (OR 6.48, 95% CI: 1.79 to 23.5). Clozapine therapy was noted in 6/7 (86%) of patients subsequently requiring immunoglobulin replacement therapy (IgRT). Marked reduction of class-switched memory B cells (CSMB) and plasmablasts were observed in clozapine-treated individuals relative to healthy age-matched controls. Clozapine duration is associated with CSMB decline. One patient discontinued clozapine, with gradual recovery of IgG levels without use of IgRT.

Conclusions Our findings are consistent with enrichment of clozapine-treatment within schizophrenic individuals referred for ICW assessment over the last 13 years. These individuals displayed clinical patterns closely resembling the primary immunodeficiency common variable immunodeficiency, however appears reversible on drug cessation. This has diagnostic, monitoring and treatment implications for psychiatry and immunology teams and directs prospective studies to address causality and the wider implications for this patient group.

  • immunodeficiency
  • psychiatry
  • antibodies
  • diagnostics
  • flow cytometry

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

View Full Text

Statistics from

Supplementary materials


  • Handling editor Tahir S Pillay.

  • Twitter @MP50683800

  • Collaborators Simon A Jones, Ana Cardus Figueras, James Walters.

  • Contributors MJP and SRAJ conceived study, and performed data extraction and analysis, and wrote the first draft. RS, KB and MB performed immunophenotyping and assisted in data extraction. DF provided support for statistical analysis. SW, EC, FMG, CRP, SZ, TT and TE-S contributed to clinical record extraction and/or interpretation of data. All authors critically reviewed and approved the final version.

  • Funding This study was funded by Cardiff University (grant number: Welsh Clinical Academic Training Fellowship).

  • Competing interests MJP is supported by the Welsh Clinical Academic Training Fellowship (WCAT) Programme and received a Wellcome Trust Institutional Strategic Support Fund (ISSF3) grant (204824/Z/16/Z). SRAJ has received support from CSL Behring, Shire, LFB, Biotest, Binding Site, Sanofi, GSK, UCB Pharma, Grifols, BPL SOBI, Weatherden, Zarodex and Octapharma for projects, advisory boards, meetings, studies, speaker and clinical trials. TE-S has received educational support, project support, advisory board fees, speaker fees and/or clinical trial support from Biotest, CSL, LFB, Mylan, Novartis, Shire and Werfen. CRP has received support to attend educational meetings from CSL Behring and ALK. The remaining authors have no relevant conflicts of interest to declare.

  • Patient consent for publication Not required.

  • Ethics approval This work was deemed as service evaluation by the institutional review board and requirement for ethical approval was waived.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. Submission to MEDRXIV (reference: 2019/007815) has been performed in line with JCP/BMJ Policy.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.