Selective Immunoglobulin M Deficiency Among Clozapine-Treated Patients

Lozano, Roberto; Marin, Reyes; Santacruz, Maria-Jesus; Pascual, Asunción

doi:10.4088/pcc.15m01782

Cited by 14 publications

(13 citation statements)

References 12 publications

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“…It has been postulated that some of these side-effects may relate to its immunomodulatory effects, 26 including agranulocytosis (cumulative incidence 0.8%) 27 . An association of clozapine with selective IgM deficiency has previously been suggested 28 identifying isolated IgM deficiency in six (18%) clozapine users and two controls (3%). Differences in study size, treatment duration, and the differential effect on immunoglobulin classes (IgM > IgA > IgG) might have contributed to the identification of the greater risks posed by reductions in all three immunoglobulin classes reported here.…”

Section: Discussionmentioning

confidence: 99%

Clozapine is associated with secondary antibody deficiency

et al. 2018

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Clozapine use was associated with significantly reduced immunoglobulin levels and an increased proportion of patients using more than five antibiotic courses in a year. Antibody testing is not included in existing clozapine monitoring programmes but may represent a mechanistic explanation and modifiable risk factor for the increased rates of pneumonia and sepsis-related mortality previously reported in this vulnerable cohort.Declaration of interestS.J. 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.

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Section: Discussionmentioning

confidence: 99%

Clozapine is associated with secondary antibody deficiency

et al. 2018

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“…Patients with SIGMD should undergo a thorough immunological evaluation, particularly with history of recurrent/severe infections. A definitive diagnosis of SIGMD, especially in children, should be established after follow-up for months to a year as in few undocumented cases serum IgM levels have normalized, and after excluding any known cause of secondary SIGMD including drug (e.g., Clozapine) induced IgM deficiency ( 88 ). Furthermore, immunoglobulin treatment is a beneficial therapeutic approach for symptomatic patients with SIGMD who also have specific IgG antibody deficiency.…”

Section: Discussionmentioning

confidence: 99%

Selective IgM Deficiency—An Underestimated Primary Immunodeficiency

Gupta

2017

Front. Immunol.

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Although selective IgM deficiency (SIGMD) was described almost five decades ago, it was largely ignored as a primary immunodeficiency. SIGMD is defined as serum IgM levels below two SD of mean with normal serum IgG and IgA. It appears to be more common than originally realized. SIGMD is observed in both children and adults. Patients with SIGMD may be asymptomatic; however, approximately 80% of patients with SIGMD present with infections with bacteria, viruses, fungi, and protozoa. There is an increased frequency of allergic and autoimmune diseases in SIGMD. A number of B cell subset abnormalities have been reported and impaired specific antibodies to Streptococcus pneumoniae responses are observed in more than 45% of cases. Innate immunity, T cells, T cell subsets, and T cell functions are essentially normal. The pathogenesis of SIGMD remains unclear. Mice selectively deficient in secreted IgM are also unable to control infections from bacterial, viral, and fungal pathogens, and develop autoimmunity. Immunological and clinical similarities and differences between mouse models of deficiency of secreted IgM and humans with SIGMD have been discussed. Patients with SIGMD presenting with recurrent infections and specific antibody deficiency responses appear to improve clinically on immunoglobulin therapy.

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“…These patients underwent continuous psychiatric, immunological and biochemical monitoring over a 5-year follow-up period (2009)(2010)(2011)(2012)(2013). The case group (n = 8) consisted of all psychiatric outpatients who displayed selective SIgMD and a control group (n = 92) consisting of randomly selected psychiatric outpatients matched to the cases on characteristics of age, sex, weight, mental health unit, diagnosis and psychiatric medication, and who had not displayed selective SIgMD (Table 1) [Lozano et al 2015].…”

Section: Therapeutic Advances In Psychopharmacologymentioning

confidence: 99%

“…SIgMD was defined by mean IgM values ⩽20mg/dl (laboratory reference range of 40–230 mg/dl) maintained across the whole follow-up period and in conjunction with normal levels of immunoglobulin (Ig) A, IgG, white blood cell count and absolute neutrophil count. IgM measurements were performed every 6 months and the data were averaged for each subject [Lozano et al . 2015].…”

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confidence: 99%