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Immunogenic properties of synthetic fragments of Sm-D protein in normal and lupus mice

Division of Rheumatology, Department of Medicine and Department of Immunology, University College London, UK

S. Muller

UPR 9021, Institut de Biologie Moleculaire et Cellulaire du CNRS, Strasbourg, France

DR Katz

Division of Rheumatology, Department of Medicine and Department of Immunology, University College London, UK

L. Wilkinson

Division of Rheumatology, Department of Medicine and Department of Immunology, University College London, UK

PR Hutchings

Division of Rheumatology, Department of Medicine and Department of Immunology, University College London, UK

DA Isenberg

Division of Rheumatology, Department of Medicine and Department of Immunology, University College London, UK

Antibodies against the Sm antigen are characteristic of systemic lupus erythematosus (SLE). They are found in 20-30% of SLE patients and it has been shown previously that up to 70% of SLE sera react with synthetic fragments 1-20 and 44-67 of the Sm-D polypeptide. To determine whether injections of these peptides might be pathogenic both were administered intraperitoneally into normal mouse strains BALB/c (H-2^d), B10/brown (H-2^k) and C57BL/6 (H-2^b) and an autoimmune strain MRL/1pr (H-2^k). IgG antibodies against peptide 1-20 were detected by ELISA in the sera of BALB/c and MRL/1pr mice but not in the sera of B10/brown and C57BL/6 mice. IgG antibodies against peptide 44-67 were found in the sera of BALB/c, B10/brown and MRL/1pr mice but not in the sera of C57BL/6 mice. Neither fragment induced a response against the whole Sm-D antigen as detected by Western blotting. Reactivity to synthetic fragments from other nuclear antigens was however detected in the sera of MRL/1pr mice, especially in those mice injected with Sm-D peptide 44-67 emulsified in Freund's adjuvant. Following immunization with Sm-D peptides, antibodies to ssDNA or dsDNA were not detected in the sera of BALB/c, B10/brown and C57BL/6 mice and in the MRL/1pr mice the naturally occurring production of these antibodies was not enhanced. No difference in IgG deposition in the renal glomeruli of the mice injected with the peptides compared with the control groups was observed. These results suggest that the humoral response to the Sm-D fragment is, at least partially, controlled by the MHC haplotype of the recipient mice, is related to dose and type of immunogen, and is also influenced by the presence of Freund's adjuvant. It is evident that although the sera of many SLE patients recognize either or both the 1-20 and 44-67 peptides, these peptides when injected into MRL/1pr mice are not directly pathogenic.

Key Words: animal models of lupus • anti-Sm antibodies • Sm-D synthetic peptides • intramolecular epitope spreading

Lupus, Vol. 6, No. 8, 656-667 (1997)
DOI: 10.1177/096120339700600807


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