Impact of Immunoglobulin Therapy in Pediatric Disease: a Review of Immune Mechanisms

Abstract

Intravenous immunoglobulin (IVIG) provides replacement therapy in immunodeficiency and immunomodulatory therapy in inflammatory and autoimmune diseases. This paper describes the immune mechanisms underlying six major non-primary immunodeficiency pediatric diseases and the diverse immunomodulatory functions of IVIG therapy. In Kawasaki disease, IVIG plays a major, proven, and effective role in decreasing aneurysm formation, which represents an aberrant inflammatory response to an infectious trigger in a genetically predisposed individual. In immune thrombocytopenia, IVIG targets the underlying increased platelet destruction and decreased platelet production. Although theoretically promising, IVIG shows no clear clinical benefit in the prophylaxis and treatment of neonatal sepsis. Limitations in research design combined with the unique neonatal immunologic environment offer explanations for this finding. Inflammation from aberrant immune activation underlies the myelinotoxic effects of Guillain-Barré syndrome. HIV-1 exerts a broad range of immunologic effects and was found to decrease serious bacterial infections in the pre-highly active anti-retroviral therapy (HAART) era, although its practical relevance in the post-HAART era has waned. Clinical and experimental data support the role of immune mechanisms in the pathogenesis of childhood epilepsy. IVIG exerts anti-epileptic effects through targeting upregulated cytokine pathways and antibodies thought to contribute to epilepsy. Applications in six additional pediatric diseases including pediatric asthma, atopic dermatitis, cystic fibrosis, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), autism, and transplantation will also be briefly reviewed. From autoimmunity to immunodeficiency, a dynamic immunologic basis underlies major pediatric diseases and highlights the broad potential of IVIG therapy.

KBG syndrome involving a single-nucleotide duplication in ANKRD11

“…A caveat is that these treatments were not administered in a blinded fashion nor was there any period of treatment with a placebo. In addition, the strength of evidence from clinical trials for efficacy of these medications for epilepsy is strongest for lamotrigine (Kwan et al 2011; Li et al 2012; Liu et al 2016), whereas the evidence is currently much weaker regarding the efficacy for autism disorder for folinic acid (Ramaekers et al 2016) and/or IVIG (Wong and White 2015). As of the publication of this study, there are ongoing clinical trials for cannabidiol (Devinsky et al 2015; Filloux 2015).…”

IVIg Therapy in PANDAS: Analysis of the Current Literature

“…Intravenous Ig provides replacement Ig in immunodeficiency and immunomodulation in the treatment of inflammatory autoimmune pediatric diseases [16]. From immunodeficiency to autoimmunity, the dynamic immunologic basis of PANDAS highlights the broad potential of high-dose IVIg therapy.…”

Guía colombiana de práctica clínica para el uso de inmonuglobulinas en el tratamiento de reemplazo e inmunomodulación

“…(GRADE C2) 173,174,175,176,177,178,179 R Se debe considerar el uso de IgIV ante sospecha clínica de epilepsia de origen autoinmune: inicio reciente ≤ 3 meses, presencia de diferente tipo de crisis, distonía faciobraquial, farmacorresistencia anticonvulsivante, antecedentes personales de autoinmunidad o en familiar en primer grado, neoplasia previa o concurrente, pródromo viral, detección de autoanticuerpos. (GRADE C2) 180,181 R Se ha utilizado 2 g/kg durante 2 a 5 días consecutivos. La dosis de mantenimiento fluctúa entre 400 mg/kg mensual y semanal durante 6 a 12 semanas.…”

“…La dosis recomendada es de 2 g/kg a lo largo de 2 días. (GRADE B2) 158,181,182,183,184,185,186,187,188,189,190,191 R El uso de IgIV puede considerarse en pacientes pediátricos con esclerosis múltiple si los corticoides están contraindicados o cuando se intenta reducir la dosis de los mismos en pacientes con frecuentes exacerbaciones. (GRADE B2) 192 Algunos estudios sugieren que la IgIV puede disminuir la actividad de la enfermedad en los adultos, incluyendo la frecuencia de recaídas.…”