Characterization of the immunoreactivity of anti-interferon alpha antibodies in myasthenia gravis patients. Epitope mapping.

Abstract

Cytokines, such as interferons (IFN), underlie many immunological functions and are increasingly implicated in disease-related symptoms and pathology. In order to study the potential roles of IFN alpha and its antagonists in autoimmune phenomena, the sera from 89 patients (aged 15-95 years, 65 females) diagnosed as having myasthenia gravis (MG) (2 months to 34 years duration) were tested for the presence of natural anti-IFN alpha-2b auto-antibodies. Sera were screened for anti-IFN alpha-2b by a sandwich-type enzyme immunoassay system. Ten (11.2%) and 6 (6.7%) sera were identified that contained positive-competing and non-competing anti-IFN alpha-2b auto-antibodies, respectively. The MG sera were further analyzed by immunobloting against reduced IFN alpha-2b and for neutralizing anti-IFN alpha activity in an antiviral assay cells system. From tested EIA positive-competing sera, 5 were shown to be positive by immunoblot and 6 sera were found to contain neutralizing anti-IFN alpha-2b. Four of the 6 neutralizing anti-IFN alpha-2b sera came from patients with thymoma-associated MG. The sera were studied for linear epitope recognition on the IFN alpha-2b molecule by a solid phase binding assay, in which overlapping peptides homologous with the entire IFN alpha-2b sequence were separately synthesized on a nitrocellulose sheet. Peptides number 2 (residues 8-21), 3 (15-28), 6 (33-46), 10 (63-76), 15 (98-112), and 21 (141-154) were immunoreactive. Peptide 21 was apparently associated with antiviral activity, although peptide 21 has not been previously described as an immunogenic determinant on the IFN alpha-2b molecule. These results indicate that neutralizing anti-IFN alpha-2b is often present in MG, particularly in cases of thymoma-associated MG, and recognize a variety of epitopes on the IFN alpha-2b molecule, including those involved in its biological activity. Two groups of IFN epitopes were described associated with patient's age but not with diseases evolution.

• Authors: Iraldo Bello-Rivero, Majel Cervantes, Yeny Torres, Joel Ferrero, Eulises Rodríguez, Jesús Pérez, Idrian García, Gisou Díaz, Pedro López-Saura
• Journal: Journal of autoimmunity (J Autoimmun) Vol. 23 Issue 1 Pg. 63-73 (Aug 2004) ISSN: 0896-8411 [Print] England
• PMID: 15236754 (Publication Type: Journal Article)
• Copyright: Copyright 2004 Elsevier Ltd.

Chemical References

• Antibodies
• Epitopes
• Interferon-alpha

Topics

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Antibodies (immunology)
• Epitope Mapping
• Epitopes (immunology)
• Female
• Humans
• Immunoblotting
• Interferon-alpha (immunology)
• Male
• Middle Aged
• Myasthenia Gravis (immunology)
• Time Factors