The immunogenic part of infliximab is the F(ab')2, but measuring antibodies to the intact infliximab molecule is more clinically useful.
Gut
; 60(1): 41-8, 2011 Jan.
Article
em En
| MEDLINE
| ID: mdl-20519742
ABSTRACT
OBJECTIVES:
To localise the immunogenic part of infliximab and evaluate the clinical usefulness of measuring antibodies against infliximab fragments.DESIGN:
Observational study. SETTINGS A specialised inflammatory bowel disease (IBD) centre in a tertiary hospital.INTERVENTIONS:
Serum was collected from patients with IBD and controls. Antibodies against whole infliximab (ATI) and against the digested Fc, F(ab')(2) and F(ab') fragments were measured by a specifically developed ELISA and by western blotting. A separate ELISA was used to determine infliximab levels in serum.RESULTS:
109 serum samples from 62 infliximab-treated patients were tested along with 64 control samples. Anti-F(ab')(2) antibodies were found in 28/42 (67%) samples with positive ATI, all from infliximab-exposed patients. Anti-F(ab')(2) antibodies were also present in 26 of the remaining 67 (39%) samples from exposed patients despite absent ATI. No specific anti-Fc antibodies were detected. Low trough infliximab level and high ATI level was found in 10/12 patients (83%) with complete loss of response to infliximab, but in only 5/14 patients (36%, p=0.02) who regained response to intensified infliximab regimen and in 2/24 patients (8%, p<0.001) in maintained remission while on 5 mg/kg/8 week infliximab treatment. Although Anti-F(ab')(2) antibodies showed similar test characteristics to ATI in patients losing response to infliximab, they were also detected in 61% of patients in maintained remission, thereby limiting their clinical usefulness. No cross reactivity to adalimumab was noted.CONCLUSIONS:
F(ab')(2) is the immunogenic fragment of infliximab. However, ATI level in serum--combined with measurement of trough infliximab level--is better correlated with the clinical response to infliximab or with its loss.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Imunológicos
/
Doenças Inflamatórias Intestinais
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Anti-Inflamatórios não Esteroides
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Anticorpos Anti-Idiotípicos
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Anticorpos Monoclonais
Tipo de estudo:
Observational_studies
Limite:
Adult
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Gut
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Israel