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Severe anaphylactic reactions to glutamic acid decarboxylase (GAD) self peptides in NOD mice that spontaneously develop autoimmune type 1 diabetes mellitus.

Pedotti R, Sanna M, Tsai M, DeVoss J, Steinman L, McDevitt H, Galli SJ - BMC Immunol. (2003)

Bottom Line: Accordingly, various protocols of "peptide immunotherapy" of T1DM are under investigation.These findings document severe anaphylaxis to self peptide preparations used in an attempt to devise immunotherapy for a spontaneous autoimmune disease.Taken together with the findings in EAE, these results suggest that peptide therapies designed to induce a TH1 to TH2 shift carry a risk for the development of anaphylactic reactivity to the therapeutic peptides.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. rpedotti@stanford.edu

ABSTRACT

Background: Insulin dependent (i.e., "type 1") diabetes mellitus (T1DM) is considered to be a T cell mediated disease in which TH1 and Tc autoreactive cells attack the pancreatic islets. Among the beta-cell antigens implicated in T1DM, glutamic acid decarboxylase (GAD) 65 appears to play a key role in the development of T1DM in humans as well as in non-obese diabetic (NOD) mice, the experimental model for this disease. It has been shown that shifting the immune response to this antigen from TH1 towards TH2, via the administration of GAD65 peptides to young NOD mice, can suppress the progression to overt T1DM. Accordingly, various protocols of "peptide immunotherapy" of T1DM are under investigation. However, in mice with experimental autoimmune encephalomyelitis (EAE), another autoimmune TH1 mediated disease that mimics human multiple sclerosis, anaphylactic shock can occur when the mice are challenged with certain myelin self peptides that initially were administered with adjuvant to induce the disease.

Results: Here we show that NOD mice, that spontaneously develop T1DM, can develop fatal anaphylactic reactions upon challenge with preparations of immunodominant GAD65 self peptides after immunization with these peptides to modify the development of T1DM.

Conclusions: These findings document severe anaphylaxis to self peptide preparations used in an attempt to devise immunotherapy for a spontaneous autoimmune disease. Taken together with the findings in EAE, these results suggest that peptide therapies designed to induce a TH1 to TH2 shift carry a risk for the development of anaphylactic reactivity to the therapeutic peptides.

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Immunization with G7, PD, or HEL/OVA peptides induced modest changes in total IgE. Total IgE serum concentrations were measured at a dilution of 1:100 by sandwich ELISA. Data are shown as mean +/- s. e. m. * = P < 0.05 vs. levels in saline-treated mice.
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Figure 3: Immunization with G7, PD, or HEL/OVA peptides induced modest changes in total IgE. Total IgE serum concentrations were measured at a dilution of 1:100 by sandwich ELISA. Data are shown as mean +/- s. e. m. * = P < 0.05 vs. levels in saline-treated mice.

Mentions: Total IgE concentrations were slightly, but significantly, higher in the peptide-immunized groups (G7, PD, or HEL/OVA) compared to those in mice injected with IFA and saline alone (Figure 3). However, the serum concentrations of total IgE were very similar in the mice that had been immunized with G7, PD or HEL/OVA peptides (Figure 3).


Severe anaphylactic reactions to glutamic acid decarboxylase (GAD) self peptides in NOD mice that spontaneously develop autoimmune type 1 diabetes mellitus.

Pedotti R, Sanna M, Tsai M, DeVoss J, Steinman L, McDevitt H, Galli SJ - BMC Immunol. (2003)

Immunization with G7, PD, or HEL/OVA peptides induced modest changes in total IgE. Total IgE serum concentrations were measured at a dilution of 1:100 by sandwich ELISA. Data are shown as mean +/- s. e. m. * = P < 0.05 vs. levels in saline-treated mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC153530&req=5

Figure 3: Immunization with G7, PD, or HEL/OVA peptides induced modest changes in total IgE. Total IgE serum concentrations were measured at a dilution of 1:100 by sandwich ELISA. Data are shown as mean +/- s. e. m. * = P < 0.05 vs. levels in saline-treated mice.
Mentions: Total IgE concentrations were slightly, but significantly, higher in the peptide-immunized groups (G7, PD, or HEL/OVA) compared to those in mice injected with IFA and saline alone (Figure 3). However, the serum concentrations of total IgE were very similar in the mice that had been immunized with G7, PD or HEL/OVA peptides (Figure 3).

Bottom Line: Accordingly, various protocols of "peptide immunotherapy" of T1DM are under investigation.These findings document severe anaphylaxis to self peptide preparations used in an attempt to devise immunotherapy for a spontaneous autoimmune disease.Taken together with the findings in EAE, these results suggest that peptide therapies designed to induce a TH1 to TH2 shift carry a risk for the development of anaphylactic reactivity to the therapeutic peptides.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. rpedotti@stanford.edu

ABSTRACT

Background: Insulin dependent (i.e., "type 1") diabetes mellitus (T1DM) is considered to be a T cell mediated disease in which TH1 and Tc autoreactive cells attack the pancreatic islets. Among the beta-cell antigens implicated in T1DM, glutamic acid decarboxylase (GAD) 65 appears to play a key role in the development of T1DM in humans as well as in non-obese diabetic (NOD) mice, the experimental model for this disease. It has been shown that shifting the immune response to this antigen from TH1 towards TH2, via the administration of GAD65 peptides to young NOD mice, can suppress the progression to overt T1DM. Accordingly, various protocols of "peptide immunotherapy" of T1DM are under investigation. However, in mice with experimental autoimmune encephalomyelitis (EAE), another autoimmune TH1 mediated disease that mimics human multiple sclerosis, anaphylactic shock can occur when the mice are challenged with certain myelin self peptides that initially were administered with adjuvant to induce the disease.

Results: Here we show that NOD mice, that spontaneously develop T1DM, can develop fatal anaphylactic reactions upon challenge with preparations of immunodominant GAD65 self peptides after immunization with these peptides to modify the development of T1DM.

Conclusions: These findings document severe anaphylaxis to self peptide preparations used in an attempt to devise immunotherapy for a spontaneous autoimmune disease. Taken together with the findings in EAE, these results suggest that peptide therapies designed to induce a TH1 to TH2 shift carry a risk for the development of anaphylactic reactivity to the therapeutic peptides.

Show MeSH
Related in: MedlinePlus