We examined the role of circulating autoantibodies in the pathogenesis of pemphigus vulgaris by passively transferring IgG fractions from five patients with pemphigus vulgaris into neonatal Balb/c mice, in doses of 1.5 to 16 mg per gram of body weight per day. Cutaneous blisters and erosions with the histologic, ultrastructural, and immunofluorescence features of pemphigus occurred in 39 to 55 mice given intraperitoneal injections of IgG from patients with pemphigus and in none of 58 control mice given normal human IgG. IgG fractions with high titers of pemphigus antibodies were most effective in inducing disease, and this effect was dose dependent. Titers of circulating IgG in mouse serum closely correlated with the extent of disease induced (P less than 0.002). This study strongly supports the proposed role of pemphigus autoantibodies in the pathogenesis of pemphigus vulgaris in human beings and demonstrates that pemphigus can be passively transferred to laboratory animals.
This article has been cited by other articles:
Gavanescu, I., Benoist, C., Mathis, D.
(2008). B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients. Proc. Natl. Acad. Sci. USA
105: 13009-13014
[Abstract][Full Text]
Heupel, W.-M., Zillikens, D., Drenckhahn, D., Waschke, J.
(2008). Pemphigus Vulgaris IgG Directly Inhibit Desmoglein 3-Mediated Transinteraction. J. Immunol.
181: 1825-1834
[Abstract][Full Text]
Lanza, A., Cirillo, N., Rossiello, R., Rienzo, M., Cutillo, L., Casamassimi, A., de Nigris, F., Schiano, C., Rossiello, L., Femiano, F., Gombos, F., Napoli, C.
(2008). Evidence of Key Role of Cdk2 Overexpression in Pemphigus Vulgaris. J. Biol. Chem.
283: 8736-8745
[Abstract][Full Text]
Diaz, L. A.
(2007). Rituximab and Pemphigus -- A Therapeutic Advance. NEJM
357: 605-607
[Full Text]
Qian, Y., Diaz, L. A., Ye, J., Clarke, S. H.
(2007). Dissecting the Anti-Desmoglein Autoreactive B Cell Repertoire in Pemphigus Vulgaris Patients. J. Immunol.
178: 5982-5990
[Abstract][Full Text]
Beissert, S., Werfel, T., Frieling, U., Bohm, M., Sticherling, M., Stadler, R., Zillikens, D., Rzany, B., Hunzelmann, N., Meurer, M., Gollnick, H., Ruzicka, T., Pillekamp, H., Junghans, V., Luger, T. A.
(2006). A Comparison of Oral Methylprednisolone Plus Azathioprine or Mycophenolate Mofetil for the Treatment of Pemphigus.. Arch Dermatol
142: 1447-1454
[Abstract][Full Text]
Stanley, J. R., Amagai, M.
(2006). Pemphigus, Bullous Impetigo, and the Staphylococcal Scalded-Skin Syndrome. NEJM
355: 1800-1810
[Full Text]
Berkowitz, P., Hu, P., Warren, S., Liu, Z., Diaz, L. A., Rubenstein, D. S.
(2006). p38MAPK inhibition prevents disease in pemphigus vulgaris mice. Proc. Natl. Acad. Sci. USA
103: 12855-12860
[Abstract][Full Text]
Rashid, K. A., Stern, J. N. H., Ahmed, A. R.
(2006). Identification of an Epitope within Human Integrin {alpha}6 Subunit for the Binding of Autoantibody and Its Role in Basement Membrane Separation in Oral Pemphigoid. J. Immunol.
176: 1968-1977
[Abstract][Full Text]
Nguyen, V. T., Arredondo, J., Chernyavsky, A. I., Pittelkow, M. R., Kitajima, Y., Grando, S. A.
(2004). Pemphigus Vulgaris Acantholysis Ameliorated by Cholinergic Agonists. Arch Dermatol
140: 327-334
[Abstract][Full Text]
Nguyen, V. T., Arredondo, J., Chernyavsky, A. I., Kitajima, Y., Pittelkow, M., Grando, S. A.
(2004). Pemphigus Vulgaris IgG and Methylprednisolone Exhibit Reciprocal Effects on Keratinocytes. J. Biol. Chem.
279: 2135-2146
[Abstract][Full Text]
Dupuy, A., Viguier, M., Bedane, C., Cordoliani, F., Blaise, S., Aucouturier, F., Bonnetblanc, J.-M., Morel, P., Dubertret, L., Bachelez, H.
(2004). Treatment of Refractory Pemphigus Vulgaris With Rituximab (Anti-CD20 Monoclonal Antibody). Arch Dermatol
140: 91-96
[Abstract][Full Text]
Tsunoda, K., Ota, T., Aoki, M., Yamada, T., Nagai, T., Nakagawa, T., Koyasu, S., Nishikawa, T., Amagai, M.
(2003). Induction of Pemphigus Phenotype by a Mouse Monoclonal Antibody Against the Amino-Terminal Adhesive Interface of Desmoglein 3. J. Immunol.
170: 2170-2178
[Abstract][Full Text]
Sitaru, C., Kromminga, A., Hashimoto, T., Brocker, E. B., Zillikens, D.
(2002). Autoantibodies to Type VII Collagen Mediate Fc{gamma}-Dependent Neutrophil Activation and Induce Dermal-Epidermal Separation in Cryosections of Human Skin. Am. J. Pathol.
161: 301-311
[Abstract][Full Text]
Sekiguchi, M., Futei, Y., Fujii, Y., Iwasaki, T., Nishikawa, T., Amagai, M.
(2001). Dominant Autoimmune Epitopes Recognized by Pemphigus Antibodies Map to the N-Terminal Adhesive Region of Desmogleins. J. Immunol.
167: 5439-5448
[Abstract][Full Text]
Caldelari, R., de Bruin, A., Baumann, D., Suter, M. M., Bierkamp, C., Balmer, V., Muller, E.
(2001). A Central Role for the Armadillo Protein Plakoglobin in the Autoimmune Disease Pemphigus Vulgaris. J. Cell Biol.
153: 823-834
[Abstract][Full Text]
Anhalt, G. J., Diaz, L. A.
(2001). Research Advances in Pemphigus. JAMA
285: 652-654
[Abstract][Full Text]
Kumari, S., Bhol, K. C., Simmons, R. K., Razzaque, M. S., Letko, E., Foster, C. S., Ahmed, A. R.
(2001). Identification of Ocular Cicatricial Pemphigoid Antibody Binding Site(s) in Human {beta}4 Integrin. IOVS
42: 379-385
[Abstract][Full Text]
Nguyen, V. T., Ndoye, A., Bassler, K. D., Shultz, L. D., Shields, M. C., Ruben, B. S., Webber, R. J., Pittelkow, M. R., Lynch, P. J., Grando, S. A.
(2001). Classification, Clinical Manifestations, and Immunopathological Mechanisms of the Epithelial Variant of Paraneoplastic Autoimmune Multiorgan Syndrome: A Reappraisal of Paraneoplastic Pemphigus. Arch Dermatol
137: 193-206
[Abstract][Full Text]
Nguyen, V. T., Ndoye, A., Grando, S. A.
(2000). Novel Human {alpha}9 Acetylcholine Receptor Regulating Keratinocyte Adhesion is Targeted by Pemphigus Vulgaris Autoimmunity. Am. J. Pathol.
157: 1377-1391
[Abstract][Full Text]
Edelson, R. L.
(2000). Pemphigus -- Decoding the Cellular Language of Cutaneous Autoimmunity. NEJM
343: 60-61
[Full Text]
Diaz, L. A., Giudice, G. J.
(2000). End of the Century Overview of Skin Blisters. Arch Dermatol
136: 106-112
[Abstract][Full Text]
Toto, P., Feliciani, C., Amerio, P., Suzuki, H., Wang, B., Shivji, G. M., Woodley, D., Sauder, D. N.
(2000). Immune Modulation in Pemphigus Vulgaris: Role of CD28 and IL-10. J. Immunol.
164: 522-529
[Abstract][Full Text]
Fan, J.-L., Memar, O., McCormick, D. J., Prabhakar, B. S.
(1999). BALB/c Mice Produce Blister-Causing Antibodies Upon Immunization with a Recombinant Human Desmoglein 3. J. Immunol.
163: 6228-6235
[Abstract][Full Text]
Udey, M. C., Stanley, J. R.
(1999). Pemphigus--Diseases of Antidesmosomal Autoimmunity. JAMA
282: 572-576
[Full Text]
Ishii, K., Amagai, M., Komai, A., Ebihara, T., Chorzelski, T. P., Jablonska, S., Ohya, K., Nishikawa, T., Hashimoto, T.
(1999). Desmoglein 1 and Desmoglein 3 Are the Target Autoantigens in Herpetiform Pemphigus. Arch Dermatol
135: 943-947
[Abstract][Full Text]
Nousari, H. C., Deterding, R., Wojtczack, H., Aho, S., Uitto, J., Hashimoto, T., Anhalt, G. J.
(1999). The Mechanism of Respiratory Failure in Paraneoplastic Pemphigus. NEJM
340: 1406-1410
[Full Text]
Lenz, P., Amagai, M., Volc-Platzer, B., Stingl, G., Kirnbauer, R.
(1999). Desmoglein 3-ELISA: A Pemphigus Vulgaris-Specific Diagnostic Tool. Arch Dermatol
135: 143-148
[Abstract][Full Text]
Liu, Z., Michael Shipley, J., Vu, T. H., Zhou, X., Diaz, L. A., Werb, Z., Senior, R. M.
(1998). Gelatinase B-deficient Mice Are Resistant to Experimental Bullous Pemphigoid. J. Exp. Med.
188: 475-482
[Abstract][Full Text]
Silos, S. A., Tamai, K., Li, K., Kivirikko, S., Kouba, D., Christiano, A. M., Uitto, J.
(1996). Cloning of the Gene for Human Pemphigus Vulgaris Antigen (Desmoglein 3), a Desmosomal Cadherin. CHARACTERIZATION OF THE PROMOTER REGION AND IDENTIFICATION OF A KERATINOCYTE-SPECIFIC cis-ELEMENT. J. Biol. Chem.
271: 17504-17511
[Abstract][Full Text]
Nguyen, V. T., Ndoye, A., Grando, S. A.
(2000). Pemphigus Vulgaris Antibody Identifies Pemphaxin. A NOVEL KERATINOCYTE ANNEXIN-LIKE MOLECULE BINDING ACETYLCHOLINE. J. Biol. Chem.
275: 29466-29476
[Abstract][Full Text]