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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)

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 revi...

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Autores principales: Ponsford, Mark James, Steven, Rachael, Bramhall, Kathyrn, Burgess, Mathew, Wijetilleka, Sonali, Carne, Emily, McGuire, Frances, Price, Colin R, Moody, Mo, Zouwail, Soha, Tahir, Tayyeb, Farewell, Daniel, El-Shanawany, Tariq, Jolles, Stephen R A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476264/
https://www.ncbi.nlm.nih.gov/pubmed/32094276
http://dx.doi.org/10.1136/jclinpath-2019-206235
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author Ponsford, Mark James
Steven, Rachael
Bramhall, Kathyrn
Burgess, Mathew
Wijetilleka, Sonali
Carne, Emily
McGuire, Frances
Price, Colin R
Moody, Mo
Zouwail, Soha
Tahir, Tayyeb
Farewell, Daniel
El-Shanawany, Tariq
Jolles, Stephen R A
author_facet Ponsford, Mark James
Steven, Rachael
Bramhall, Kathyrn
Burgess, Mathew
Wijetilleka, Sonali
Carne, Emily
McGuire, Frances
Price, Colin R
Moody, Mo
Zouwail, Soha
Tahir, Tayyeb
Farewell, Daniel
El-Shanawany, Tariq
Jolles, Stephen R A
author_sort Ponsford, Mark James
collection PubMed
description 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.
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spelling pubmed-74762642020-09-30 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) Ponsford, Mark James Steven, Rachael Bramhall, Kathyrn Burgess, Mathew Wijetilleka, Sonali Carne, Emily McGuire, Frances Price, Colin R Moody, Mo Zouwail, Soha Tahir, Tayyeb Farewell, Daniel El-Shanawany, Tariq Jolles, Stephen R A J Clin Pathol Original Research 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. BMJ Publishing Group 2020-09 2020-02-24 /pmc/articles/PMC7476264/ /pubmed/32094276 http://dx.doi.org/10.1136/jclinpath-2019-206235 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/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: https://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Research
Ponsford, Mark James
Steven, Rachael
Bramhall, Kathyrn
Burgess, Mathew
Wijetilleka, Sonali
Carne, Emily
McGuire, Frances
Price, Colin R
Moody, Mo
Zouwail, Soha
Tahir, Tayyeb
Farewell, Daniel
El-Shanawany, Tariq
Jolles, Stephen R A
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)
title 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)
title_full 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)
title_fullStr 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)
title_full_unstemmed 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)
title_short 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)
title_sort 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)
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476264/
https://www.ncbi.nlm.nih.gov/pubmed/32094276
http://dx.doi.org/10.1136/jclinpath-2019-206235
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