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

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.

• Authors: Federica Barbati, Edoardo Marrani, Beatrice Volpi, Giovanna Ferrara, Lorenzo Lodi, Maria Vincenza Mastrolia, Clementina Canessa, Ilaria Maccora, Gabriele Simonini, Chiara Azzari, Silvia Ricci
• Journal: European journal of pediatrics (Eur J Pediatr) Vol. 181 Issue 9 Pg. 3439-3448 (Sep 2022) ISSN: 1432-1076 [Electronic] Germany
• PMID: 35834043 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Immunoglobulin G
• Immunosuppressive Agents
• Mycophenolic Acid

Topics

• Agammaglobulinemia (chemically induced, drug therapy)
• Child
• Disease Susceptibility (chemically induced)
• Humans
• Immunoglobulin G
• Immunosuppressive Agents (adverse effects)
• Mycophenolic Acid (adverse effects)
• Retrospective Studies