HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tüzün, E. Articles by Christadoss, P. Search for Related Content PubMed PubMed Citation Articles by Tüzün, E. Articles by Christadoss, P.

Circulating Immune Complexes Augment Severity of Antibody-Mediated Myasthenia Gravis in Hypogammaglobulinemic RIIIS/J Mice¹

Erdem Tüzün^*, Benjamin G. Scott^*, Huan Yang^*, Bo Wu^2,, Elzbieta Goluszko^3,*, Michelle Guigneaux, Stephen Higgs and Premkumar Christadoss^4,*

Departments of ^* Microbiology and Immunology and Pathology, University of Texas Medical Branch, Galveston, TX 77555; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390; and Sealy Center for Molecular Sciences, University of Texas Medical Branch Genomics Core, Galveston, TX 77555

Experimental autoimmune myasthenia gravis (EAMG) is severe in RIIIS/J mice, despite a significant B cell immunodeficiency and a massive TCR V gene deletion. Severity of EAMG in RIIIS/J mice is greater than MHC-identical (H-2^r) B10.RIII mice, suggesting the influence of non-MHC genes as an EAMG-potentiating factor in this strain. To delineate the role of deleted TCR V genes in RIIIS/J mice, we obtained (RIIIS/J x B10.RIII)F₁ (V^b/c) x RIIIS/J (V^c) backcross mice using Mendelian genetic methods and immunized them with acetylcholine receptor. EAMG susceptibility was not elevated in mice with V^c genotype having 70% V gene deletion. Next, we performed microarray analysis on 12,488 spleen cDNAs obtained from spleens of naive RIIIS/J and B10.RIII mice. In RIIIS/J mice, 263 cDNAs were overexpressed and 303 cDNAs were underexpressed greater than 2-fold, compared with B10.RIII mice. TCR gene expression was augmented, whereas NK receptor, C1q, and C3 gene expressions were diminished in RIIIS/J mice. RIIIS/J mice also had increased lymph node T cell counts, elevated serum anti-AChR Ab levels, and serum C3 and C1q-conjugated circulating immune complex levels. A direct correlation between increased serum C1q-conjugated circulating immune complex levels and disease severity was observed in RIIIS/J mice.

This article has been cited by other articles:

				H. Yang, E. Tuzun, D. Alagappan, X. Yu, B. G. Scott, A. Ischenko, and P. Christadoss IL-1 Receptor Antagonist-Mediated Therapeutic Effect in Murine Myasthenia Gravis Is Associated with Suppressed Serum Proinflammatory Cytokines, C3, and Anti-Acetylcholine Receptor IgG1 J. Immunol., August 1, 2005; 175(3): 2018 - 2025. [Abstract] [Full Text] [PDF]