| First Author | Semerano L | Year | 2013 |
| Journal | Clin Exp Immunol | Volume | 172 |
| Issue | 1 | Pages | 54-62 |
| PubMed ID | 23480185 | Mgi Jnum | J:194898 |
| Mgi Id | MGI:5475037 | Doi | 10.1111/cei.12040 |
| Citation | Semerano L, et al. (2013) Protection from articular damage by passive or active anti-tumour necrosis factor (TNF)-alpha immunotherapy in human TNF-alpha transgenic mice depends on anti-TNF-alpha antibody levels. Clin Exp Immunol 172(1):54-62 |
| abstractText | Active anti-tumour necrosis factor (TNF)-alpha immunization with the kinoid of TNF-alpha (TNF-K) induces polyclonal anti-TNF-alpha antibodies and ameliorates arthritis in human TNF-alpha (hTNF-alpha) transgenic mice (TTg). We compared the efficacy of TNF-K to that of infliximab (IFX) and of TNF-K and IFX co-administration, and evaluated whether the titres of anti-hTNF-alpha antibodies induced by immunization were a determinant of TNF-K efficacy. Forty-eight TTg mice received one of the following treatments: TNF-K immunization (TNF-K group); weekly IFX throughout the study duration (IFXw0-15); TNF-K plus weekly IFX for 4 weeks (TNF-K + IFX); and weekly IFX for 4 weeks (IFXw0-4); PBS. Animals were killed at week 16. Anti-hTNF-alpha antibody titres and clinical and histological scores were compared. All TNF-K immunized mice (TNF-K and TNF-K + IFX) produced anti-hTNF-alpha antibodies. Titres were higher in TNF-K versus TNF-K + IFX (P < 0.001) and correlated inversely with histological inflammation (R = -0.78; P = 0.0001) and destruction (R = -0.67; P = 0.001). TNF-K + IFX had higher histological inflammation and destruction versus TNF-K (P < 0.05). A receiver operating characteristic (ROC) analysis of anti-hTNF-alpha antibody titres identified the criterion cut-off value to discriminate most effectively between the TNF-K and TNF-K + IFX groups. Mice with high versus low titres had less histological inflammation and destruction (P < 0.05). In a model of TNF-alpha-dependent arthritis, protection from articular damage by TNF-K correlates with the titres of induced anti-hTNF-alpha antibodies. The co-administration of TNF-K and a short course of infliximab does not result in less articular damage versus solely TNF-K, due probably to lower anti-hTNF-alpha antibody production. These results are relevant for future development of active anti-TNF-alpha immunization in human disease. |
