Shared Early Autoantibody Recognition Events in the Development of Anti‐Sm B/B' in Human Lupus

Many aspects of the immune maturation are uncharted. For ordinary human autoimmune systems there are no complete descriptions of the progression from an initial antigenic epitope to a maximally complex immune response. In this study we have exploited a large serial collection of human sera to invest...

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Bibliographic Details
Published in:Scandinavian journal of immunology 1999-11, Vol.50 (5), p.447-455
Main Authors: Arbuckle, M R, Reichlin, M, Harley, J B, James, J A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Autoantibodies - blood
Autoantigens - genetics
Binding Sites
Cross Reactions
Epitope Mapping
Epitopes - genetics
Humans
Lupus Erythematosus, Systemic - genetics
Lupus Erythematosus, Systemic - immunology
Molecular Sequence Data
Peptide Fragments - genetics
Peptide Fragments - immunology
Ribonucleoproteins, Small Nuclear
Sm B/B' antigen
snRNP Core Proteins
Time Factors
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Summary:Many aspects of the immune maturation are uncharted. For ordinary human autoimmune systems there are no complete descriptions of the progression from an initial antigenic epitope to a maximally complex immune response. In this study we have exploited a large serial collection of human sera to investigate the development of the anti‐Sm autoimmune response in systemic lupus ertythematosus (SLE). The results suggest a similar, if not virtually identical, stepwise progression in the early humoral immune maturation of anti‐Sm. The amino acid sequence PPPGMRPP comprises the first epitope in the anti‐Sm B/B'response and its close relative, PPPGMRGP, the second. Epitopes are subsequently enlarged by the incorporation of neighbouring amino acids. The third and fourth epitopes are also recognised by an antibody in a nearly identical sequence in different lupus patients. A column absorption with PPPGMRPP demonstrates that the epitope spreading among the first four early epitopes appears to occur by the sequential generation of cross‐reactive antibodies. Unexpectedly, epitope spreading in this system occurs in a predictable fashion by involving essentially the same sequence of antigenic structures from person to person. In addition, these data support the lupus anti‐Sm antibodies originating against a single antigenic structure and, hence, strongly support a unifying mechanism in the generation of these autoantibodies.
ISSN:0300-9475
1365-3083
DOI:10.1046/j.1365-3083.1999.00640.x