Anti-Inflammatory and Immunomodulatory Effect of High-Dose Immunoglobulins in Children: From Approved Indications to Off-Label Use

Authors: Conti, F; Moratti, M; Leonardi, L; Catelli, A; Bortolamedi, E; Filice, E; Fetta, A; Fabi, M; Facchini, E; Cantarini, ME; Miniaci, A; Cordelli, DM; Lanari, M; Pession, A; Zama, D

Affiliations: Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy. Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy. Specialty School of Paediatrics, University of Bologna, 40138 Bologna, Italy. Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy. Specialty School of Paediatrics, University of Bologna, 40138 Bologna, Italy. Department of Pediatrics, Maggiore Hospital, 40133 Bologna, Italy. IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria dell’Età Pediatrica, 40139 Bologna, Italy. Paediatric Emergency Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy. Pediatric Oncology and Hematology Unit « Lalla Seràgnoli », IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.

Publication: Cells. 2023. 12

ABSTRACT: BACKGROUND: The large-scale utilization of immunoglobulins in patients with inborn errors of immunity (IEIs) since 1952 prompted the discovery of their key role at high doses as immunomodulatory and anti-inflammatory therapy, in the treatment of IEI-related immune dysregulation disorders, according to labelled and off-label indications. Recent years have been dominated by a progressive imbalance between the gradual but constant increase in the use of immunoglobulins and their availability, exacerbated by the SARS-CoV-2 pandemic. OBJECTIVES: To provide pragmatic indications for a need-based application of high-dose immunoglobulins in the pediatric context. SOURCES: A literature search was performed using PubMed, from inception until 1st August 2023, including the following keywords: anti-inflammatory; children; high dose gammaglobulin; high dose immunoglobulin; immune dysregulation; immunomodulation; immunomodulatory; inflammation; intravenous gammaglobulin; intravenous immunoglobulin; off-label; pediatric; subcutaneous gammaglobulin; subcutaneous immunoglobulin. All article types were considered. IMPLICATIONS: In the light of the current imbalance between gammaglobulins’ demand and availability, this review advocates the urgency of a more conscious utilization of this medical product, giving indications about benefits, risks, cost-effectiveness, and administration routes of high-dose immunoglobulins in children with hematologic, neurologic, and inflammatory immune dysregulation disorders, prompting further research towards a responsible employment of gammaglobulins and improving the therapeutical decisional process.