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Beta2-microglobulin-deficient mice are resistant to bullous pemphigoid.

Liu Z, Roopenian DC, Zhou X, Christianson GJ, Diaz LA, Sedmak DD, Anderson CL - J. Exp. Med. (1997)

Bottom Line: Recent understanding of the mechanism of immunoglobulin G (IgG) catabolism has yielded new insight into antibody-mediated diseases.Such an hypothesis would predict that beta2m-deficient mice would also be resistant to experimental bullous pemphigoid, a disease with a pathogenesis thought to be much simpler than SLE, being the result of antibody directed toward a pathogenic epitope on the epidermal hemidesmosome that anchors basal keratinocytes to the basement membrane.These data would indicate that autoantibody-mediated inflammation might be prevented or controlled by appropriate modulation of FcRn function.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 43226, USA. zhiliu@post.its.mew.edu

ABSTRACT
Recent understanding of the mechanism of immunoglobulin G (IgG) catabolism has yielded new insight into antibody-mediated diseases. We proposed that beta2-microglobulin (beta2m)-deficient mice have been protected from systemic lupus erythematosis (SLE)-like syndromes because they lack the beta2m-associated IgG protection receptor (FcRn) and therefore catabolize IgG, including pathogenic IgG autoantibodies, considerably more rapidly than normal mice. Such an hypothesis would predict that beta2m-deficient mice would also be resistant to experimental bullous pemphigoid, a disease with a pathogenesis thought to be much simpler than SLE, being the result of antibody directed toward a pathogenic epitope on the epidermal hemidesmosome that anchors basal keratinocytes to the basement membrane. To test this hypothesis, we administered pathogenic rabbit antibody directed toward the hemidesmosome to beta2m-deficient mice and to normal control mice, both intraperitoneally and intradermally, and assessed the mice clinically, histologically, and immunologically for manifestations of skin disease. We found that the beta2m-deficient mice were protected when the antibody was given intraperitoneally whereas intradermal administration resulted in blisters only slightly less severe than those seen in normal mice. These data would indicate that autoantibody-mediated inflammation might be prevented or controlled by appropriate modulation of FcRn function.

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Time course (6–24 h after injection) of anti-mBP180 IgG  survival in β2m−/− mice. β2m−/− (closed squares) and β2m+/− (closed circles)  mice were injected intraperitoneally with pathogenic rabbit anti-mBP180  IgG and serum samples were collected at 6, 12, and 24 h after injection  and assayed for rabbit IgG by ELISA. n = 5 for each point. *P <0.001,  Student's t test for paired samples.
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Figure 3: Time course (6–24 h after injection) of anti-mBP180 IgG survival in β2m−/− mice. β2m−/− (closed squares) and β2m+/− (closed circles) mice were injected intraperitoneally with pathogenic rabbit anti-mBP180 IgG and serum samples were collected at 6, 12, and 24 h after injection and assayed for rabbit IgG by ELISA. n = 5 for each point. *P <0.001, Student's t test for paired samples.

Mentions: Indirect IF showed a lower level of circulating rabbit IgG in β2m−/− mice (titer = 1:1,280) than control groups (titer >1:5,120 for all three groups of mice). ELISA further demonstrated significant changes in circulating R621 IgG in β2m−/− mice at different timepoints after injection (Fig. 3). R621 IgG levels in β2m+/− mice were 1.18 ± 0.09, 2.32 ± 0.06, 1.83 ± 0.19, at 6 h, 12 h, 24 h, respectively, after intraperitoneal injection. In contrast, R621 IgG levels in β2m−/− mice were 0.89 ± 0.08, 1.40 ± 0.14, 1.04 ± 0.10, at 6 h, 12 h, 24 h, respectively, after intraperitoneal IgG injection. There were significant reductions of circulating R621 IgG between β2m−/− and β2m+/− at 12 h (40%; P <0.001) and 24 h (43%; P <0.001) after injection.


Beta2-microglobulin-deficient mice are resistant to bullous pemphigoid.

Liu Z, Roopenian DC, Zhou X, Christianson GJ, Diaz LA, Sedmak DD, Anderson CL - J. Exp. Med. (1997)

Time course (6–24 h after injection) of anti-mBP180 IgG  survival in β2m−/− mice. β2m−/− (closed squares) and β2m+/− (closed circles)  mice were injected intraperitoneally with pathogenic rabbit anti-mBP180  IgG and serum samples were collected at 6, 12, and 24 h after injection  and assayed for rabbit IgG by ELISA. n = 5 for each point. *P <0.001,  Student's t test for paired samples.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199010&req=5

Figure 3: Time course (6–24 h after injection) of anti-mBP180 IgG survival in β2m−/− mice. β2m−/− (closed squares) and β2m+/− (closed circles) mice were injected intraperitoneally with pathogenic rabbit anti-mBP180 IgG and serum samples were collected at 6, 12, and 24 h after injection and assayed for rabbit IgG by ELISA. n = 5 for each point. *P <0.001, Student's t test for paired samples.
Mentions: Indirect IF showed a lower level of circulating rabbit IgG in β2m−/− mice (titer = 1:1,280) than control groups (titer >1:5,120 for all three groups of mice). ELISA further demonstrated significant changes in circulating R621 IgG in β2m−/− mice at different timepoints after injection (Fig. 3). R621 IgG levels in β2m+/− mice were 1.18 ± 0.09, 2.32 ± 0.06, 1.83 ± 0.19, at 6 h, 12 h, 24 h, respectively, after intraperitoneal injection. In contrast, R621 IgG levels in β2m−/− mice were 0.89 ± 0.08, 1.40 ± 0.14, 1.04 ± 0.10, at 6 h, 12 h, 24 h, respectively, after intraperitoneal IgG injection. There were significant reductions of circulating R621 IgG between β2m−/− and β2m+/− at 12 h (40%; P <0.001) and 24 h (43%; P <0.001) after injection.

Bottom Line: Recent understanding of the mechanism of immunoglobulin G (IgG) catabolism has yielded new insight into antibody-mediated diseases.Such an hypothesis would predict that beta2m-deficient mice would also be resistant to experimental bullous pemphigoid, a disease with a pathogenesis thought to be much simpler than SLE, being the result of antibody directed toward a pathogenic epitope on the epidermal hemidesmosome that anchors basal keratinocytes to the basement membrane.These data would indicate that autoantibody-mediated inflammation might be prevented or controlled by appropriate modulation of FcRn function.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 43226, USA. zhiliu@post.its.mew.edu

ABSTRACT
Recent understanding of the mechanism of immunoglobulin G (IgG) catabolism has yielded new insight into antibody-mediated diseases. We proposed that beta2-microglobulin (beta2m)-deficient mice have been protected from systemic lupus erythematosis (SLE)-like syndromes because they lack the beta2m-associated IgG protection receptor (FcRn) and therefore catabolize IgG, including pathogenic IgG autoantibodies, considerably more rapidly than normal mice. Such an hypothesis would predict that beta2m-deficient mice would also be resistant to experimental bullous pemphigoid, a disease with a pathogenesis thought to be much simpler than SLE, being the result of antibody directed toward a pathogenic epitope on the epidermal hemidesmosome that anchors basal keratinocytes to the basement membrane. To test this hypothesis, we administered pathogenic rabbit antibody directed toward the hemidesmosome to beta2m-deficient mice and to normal control mice, both intraperitoneally and intradermally, and assessed the mice clinically, histologically, and immunologically for manifestations of skin disease. We found that the beta2m-deficient mice were protected when the antibody was given intraperitoneally whereas intradermal administration resulted in blisters only slightly less severe than those seen in normal mice. These data would indicate that autoantibody-mediated inflammation might be prevented or controlled by appropriate modulation of FcRn function.

Show MeSH
Related in: MedlinePlus