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As mucosal administration of an antigen may induce immune tolerance we have evaluated the Ärzte behandeln Krampfadern of mucosal antigen exposure to achieve tolerance to FVIII.
The development of anti-FVIII inhibitors, cytokine production by splenocytes in vitroand adoptive transfer assays were analyzed. Based on these results, the potential use of FVIII-specific mucosal tolerance induction as an immunotherapy treatment for anti-FVIII inhibitor development warrants further investigation, venipuncture Krampf.
Inhibitors develop due to the initiation of an adaptive immune response against the FVIII antigen, which is perceived as a foreign protein. However, several disadvantages are associated with ITI regimens including the high cost of FVIII products, the requirement for frequent venous access, an inability to tolerize some patients, and the lack venipuncture Krampf affordable access to FVIII for tolerance induction in developing countries, venipuncture Krampf.
The process of mucosal tolerance has evolved to prevent inappropriate immune responses against gut microflora and food antigens. Mucosal tolerance can also be achieved via nasal antigen administration [ 8 Varizen oder Kettenrad, which requires less antigen than the oral route, venipuncture Krampf, and may be more effective at tolerance induction [ 13 ].
This represents a novel therapeutic approach to the venipuncture Krampf of anti-FVIII inhibitor development and suggests that additional evaluation of this tolerizing approach is warranted, venipuncture Krampf.
All mouse experiments were performed in accordance with the regulations of the Canadian Council for Animal Care, and the Queen's University Animal Care Committee approved all animal protocols. Control mice were simultaneously treated with PBS.
Mice were immunized subcutaneously s. Peripheral whole blood samples were obtained via the saphenous vein. Diluted mouse plasma samples were mixed with normal human plasma in a 1: All remaining incubations were performed at room temperature.
Plates were washed with 0. Results are expressed as the means of triplicate values, venipuncture Krampf. Statistical comparisons of experimental groups were evaluated with a Student's t -test. Oral tolerance induction protocols involve mucosal antigen administration followed by peripheral antigen challenge with venipuncture Krampf. A dose of 0. Mice were immunized using IFA in order to achieve consistent and parallel immunization.
A peptide cocktail containing 0. The peptide cocktails offered no protective effect venipuncture Krampf inhibitor development, and mice that received the peptide cocktails developed anti-FVIII inhibitor titers similar to PBS-treated controls Fig.
The intranasal venipuncture Krampf of antigen administration in mucosal tolerance induction studies venipuncture Krampf been shown to be effective at up to fold lower antigen doses than the oral route [ 13 ], venipuncture Krampf. No significant difference in anti-FVIII inhibitor venipuncture Krampf was detected between the four groups of mice. FVIII challenge, venipuncture Krampf, produced Figures display venipuncture Krampf production by splenocytes from mice dosed with: Splenocytes from individual mice killed at the same time were pooled, and the errors bars represent SEM between experiments performed on these different splenocyte pools.
This demonstrates that recognition of the FVIII C2 domain by the cultured splenocytes is directly responsible for the up-regulation in IL production in vitro and illustrates that, despite the production of neutralizing anti-FVIII inhibitors in this group of mice, partial tolerance venipuncture Krampf induced to venipuncture Krampf C2 domain of the FVIII molecule, venipuncture Krampf.
The development of FVIII inhibitory antibodies represents the most significant treatment-related complication in hemophilia A. In this study, we evaluated the efficacy of inducing immunologic tolerance to FVIII via mucosal antigen exposure, and have demonstrated that hemophilic mice can be partially protected against anti-FVIII inhibitor development by multiple oral or nasal doses of the purified FVIII C2 domain. IL has also been shown to negatively regulate T-cell proliferation and inflammatory responses, and is required for mucosal tolerance induction, as illustrated by the failure of oral tolerance in IL KO animals [ 29 ].
These peptides were chosen for use in this study due to the fact that they are known T-cell and B-cell epitopes [ 24,25 ], venipuncture Krampf. This peptide cocktail may have failed to induce tolerance for several reasons: Other studies that have analyzed oral tolerance induction to FVIII have shown that breast-feeding, which may transmit FVIII peptides to the infant, is not protective against inhibitor development [ 14,15 ].
Preliminary reports of mucosal tolerance to clotting factors have been presented previously [ 31,32 ] but the present study is the first to demonstrate that tolerance to the FVIII C2 domain, which is of immunological significance in humans, can be induced via the mucosal route and can protect venipuncture Krampf mice against subsequent high-titer anti-FVIII inhibitor development.
The results of this study indicate that mucosal tolerance induction therapy, venipuncture Krampf, in which immunogenic regions of the FVIII protein are administered for the prevention or treatment of anti-FVIII inhibitor development, warrants further investigation. Ruth Maron provided technical advice on the design of the mucosal tolerance studies.
By continuing to browse this site you agree to us using cookies as described in About Cookies Remove maintenance message. Family history and inherited thrombophilia Next article in issue: Open Figure Download Powerpoint slide. Close article support pane.
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Induction of partial immune tolerance to factor VIII through prior mucosal exposure to the application of pressure to the venipuncture site for 3–5 min.
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