Effects of immunomodulation in classic infantile Pompe patients with high antibody titers.
Orphanet J Rare Dis
; 14(1): 71, 2019 03 22.
Article
em En
| MEDLINE
| ID: mdl-30902109
ABSTRACT
PURPOSE:
To evaluate whether immunomodulation can eliminate high sustained antibody levels, and thereby improve clinical outcome in classic infantile Pompe patients receiving enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA).METHODS:
Three patients (two cross-reactive immunologic material (CRIM) negative) with high sustained antibodies received a three-week treatment protocol with Rituximab and Bortezomib, followed by daily Rapamycin and monthly IVIG. Patients received 40 mg/kg/week rhGAA. Antibody titers were measured using ELISA. Neutralizing effects on cellular uptake were determined. Clinical efficacy was measured in terms of (ventilator-free) survival, reduction in left ventricular mass index (LVMI) and improvement in motor function.RESULTS:
Before immunomodulation anti-rhGAA antibody titers ranged from 1156,250 to 1781,250 and at last assessment from 131,250 to 1156,250. Neutralizing effects of anti-rhGAA antibody titers (observed in two patients) disappeared. Infusion-associated reactions were no longer present. Immunomodulation resulted in substantial increases of aspartate transaminase, alanine transaminase, and creatine kinase levels. The two CRIM-negative patients who could walk at start of immunomodulation maintained their ability to walk; the patient who had lost this ability did not regain it.CONCLUSIONS:
To some extent, the immunomodulation protocol used in our study reduced antibody titers, but it did not eliminate them. Overall, there have been few reports on secondary immunomodulation, and various protocols have been applied. Future research should seek to identify the most successful immunomodulation protocol in patients with high sustained titers.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Depósito de Glicogênio Tipo II
/
Fatores Imunológicos
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Orphanet J Rare Dis
Assunto da revista:
MEDICINA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Holanda