Importin beta: A novel autoantigen in human autoimmunity identified by screening random peptide libraries on phage

By screening random peptide libraries (RPLs) with sera of Type 1 diabetes (T1D) patients, we previously identified 5 disease-specific ‘mimotopes’ displayed on phages (phagotopes). We already characterised 1 phagotope (CH1p), as an epitope of human osteopontin, an autoantigen expressed within the som...

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Bibliographic Details
Published in:Journal of autoimmunity 2006-05, Vol.26 (3), p.197-207
Main Authors: Ola, Thomas O., Biro, Paul A., Hawa, Mohammed I., Ludvigsson, Johnny, Locatelli, Mattia, Puglisi, Maria Ausiliatrice, Bottazzo, Gian Franco, Fierabracci, Alessandra
Format: Article
Language:English
Subjects:
Animals
Autoantigens
Autoantigens - genetics
Autoantigens - immunology
Autoimmunity
Base Sequence
beta Karyopherins - genetics
beta Karyopherins - immunology
Biological and medical sciences
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 1 - immunology
Enzyme-Linked Immunosorbent Assay - methods
Fundamental and applied biological sciences. Psychology
Fundamental immunology
General aspects
Humans
Immunohistochemistry
Immunopathology
Islets of Langerhans - cytology
Islets of Langerhans - immunology
Medical sciences
MEDICIN
MEDICINE
Molecular Sequence Data
Peptide libraries
Peptide Library
Rabbits
Radioimmunoassay
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Summary:By screening random peptide libraries (RPLs) with sera of Type 1 diabetes (T1D) patients, we previously identified 5 disease-specific ‘mimotopes’ displayed on phages (phagotopes). We already characterised 1 phagotope (CH1p), as an epitope of human osteopontin, an autoantigen expressed within the somatostatin cells of human islets. In this paper, we report the characterization of the second phagotope, 195Dyn, by immunohistochemistry, Western Blotting and screening of a human islet cDNA library using rabbit anti-195Dyn antibodies. The 195Dyn mimotope was detected in human islets. The screening of a λgt11 cDNA library from human islets has identified a clone, which corresponded to human importin beta. ELISA detected autoantibodies against this protein in sera of around 60% of TD1 patients and in 30% of patients affected by other autoimmune diseases. In summary, RPLs technology proved again successful in identifying another novel autoantigen (importin beta), whose significance in the autoimmune process remains to be fully elucidated.
ISSN:0896-8411
1095-9157
1095-9157
DOI:10.1016/j.jaut.2006.01.003