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Mycophenolate mofetil-induced hypogammaglobulinemia and infectious disease susceptibility in pediatric patients with chronic rheumatic disorders: a monocentric retrospective study

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Abstract

Mycophenolate mofetil (MMF) is an immunosuppressive drug used for the treatment of autoimmune rheumatological diseases. To test the risk of hypothetical drug-induced hypogammaglobulinemia, the aim of this study was to report the trend of the immunoglobulin (Ig) values and of the infectious diseases in children treated with MMF. This study retrospectively evaluated demographic, clinical, and laboratory data of a cohort of patients affected by a chronic rheumatic disease receiving MMF, followed at the Rheumatology Unit of Meyer Children Hospital, Florence. A total of 29 pediatric patients were enrolled. In patients with normal values of immunoglobulins at the baseline, treatment with MMF resulted in a statistically significant reduction of the IgG levels (p = 0.0058) and in a decrease of IgM levels not reaching statistical significance. The levels of IgA were not affected. During the follow-up, seven patients developed an humoral immune defect. The univariate analysis did not identify any risk factors related to the iatrogenic hypogammaglobulinemia. The infection rate during MMF therapy was significantly higher than the 12-month period before therapy (p = 0.006), while the severe infections did not significantly increase (p = 0.1818), even considering only the patients with hypogammaglobulinemia.

Conclusion: In pediatric patients with chronic rheumatic diseases, immunological first level tests and serological analyses to screen the protection against the common childhood pathogens are suggested before starting an immunosuppressive drug. These patients should also complete the vaccination schedule. In patients treated with MMF a strict monitoring of Ig is required during treatment and after discontinuation of the drug.

What is Known:

• MMF is an immunosuppressive drug initially used for the treatment of the graft-versus-host disease.

• Mycophenolic acid is an inhibitor of inosine-5′-monophosphate dehydrogenase, expressed in lymphocytes; therefore, MMF could impair the immune system function.

What is New:

• MMF resulted in a reduction of IgG and an increase of not severe infection rate.

• Immunological first level tests, including Ig, lymphocyte subpopulations, and antibody response to vaccines, are suggested in pediatric patients before starting MMF; a strict monitoring of Ig is important before, during, and after MMF treatment.

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Availability of data and material

Materials described in the manuscript, including all relevant raw data, will be freely available to any researcher and reader.

Abbreviations

AIFA:

Italian Medicines Agency

AZA:

Azathioprine

CVID:

Common variable immunodeficiency

EBV:

Epstein-Barr virus

EMA:

European Medicines Agency

HSV:

Herpes simplex virus

Ig:

Immunoglobulin

IQR:

Interquartile range

MMF:

Mycophenolate mofetil

SLE:

Systemic Lupus Erythematosus

SSc:

Systemic Sclerosis

SD:

Standard deviations

URTI:

Upper respiratory tract infections

UTI:

Urinary tract infections

VZV:

Varicella Zoster virus

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Author information

Author notes

  1. Federica Barbati and Edoardo Marrani contributed equally.

Authors and Affiliations

  1. Department of Pediatrics, Immunology Unit, Anna Meyer Children’s University Hospital, Viale Pieraccini 24, 50139, Florence, Italy

    Federica Barbati, Lorenzo Lodi, Clementina Canessa, Chiara Azzari & Silvia Ricci

  2. Department of Pediatrics, Rheumatology Unit, Meyer Children’s University Hospital, Florence, Italy

    Edoardo Marrani, Maria Vincenza Mastrolia, Ilaria Maccora & Gabriele Simonini

  3. Department of Health Sciences, University of Florence, Florence, Italy

    Beatrice Volpi

  4. Pediatrics and Neonatology Unit, S. Maria Annunziata Hospital, Azienda USL Toscana Centro, Florence, Italy

    Giovanna Ferrara

Authors
  1. Federica Barbati
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Contributions

Dr Federica Barbati, Dr Edoardo Marrani, and Dr Beatrice Volpi participated in literature search, article selection, data collection, and writing—original draft preparation. Dr Giovanna Ferrara, Dr Lorenzo Lodi, Dr Maria Vincenza Mastrolia, Dr Clementina Canessa, and Dr Ilaria Maccora contributed to the conceptualization, writing—review and editing. Prof Gabriele Simonini, Prof Chiara Azzari, and Dr Silvia Ricci supervised the design and execution of the study and participated in conceptualization, methodology, writing—review and editing.

Corresponding author

Correspondence to Federica Barbati.

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Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. As the study has an observational retrospective design, for this type of study, formal consent was not required.

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Not applicable.

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Written informed consent was obtained from the parents.

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The authors declare no competing interests.

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Communicated by Nicole Ritz

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Barbati, F., Marrani, E., Volpi, B. et al. Mycophenolate mofetil-induced hypogammaglobulinemia and infectious disease susceptibility in pediatric patients with chronic rheumatic disorders: a monocentric retrospective study. Eur J Pediatr 181, 3439–3448 (2022). https://doi.org/10.1007/s00431-022-04560-2

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  • DOI: https://doi.org/10.1007/s00431-022-04560-2

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