The human Ku autoantigen shares amino acid sequence homology with fungal, but not bacterial and viral, proteins.
BACKGROUND
Molecular mimicry between autoantigens and microbial antigens is a possible triggering mechanism of autoimmunity. Human Ku is a DNA-associated autoantigen targeted by autoantibodies in patients with systemic lupus erythematosus and related disorders; available data are consistent with a role of molecular mimicry in the pathogenesis of Anti-Ku autoimmunity, but no research exist on this topic.


OBJECTIVE
We aimed to define the most probable microbial triggers of anti-Ku autoimmunity via molecular mimicry. Materials and methods. We performed a computer-assisted search for amino acid sequence homologies between the two subunits of human Ku and proteins of known human pathogens.


RESULTS
Some fungal, but no bacterial or viral, proteins have statistically significant amino acid sequence homology with the p70 or p80 subunit of Ku. Twenty-six fungal proteins contain long segments highly homologous to p70 (14 proteins) or p80 (12 proteins) and belong to human pathogens (Aspergillus clavatus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger, Aspergillus terreus, Chaetomium globosum, Cryptococcus neoformans, Coccidioides immitis, Malassezia globosa, Neosartorya fischeri, Penicillium chrysogenum Wisconsin, Penicillium marneffei, and Yarrowia lipolytica). Twelve p70-homologous and eleven p80-homologous segments span at least one T cell epitope-containing part of the respective human Ku subunit (in the other cases, overlap is almost complete).


CONCLUSIONS
We postulate that, in genetically predisposed persons, infection by the above fungi can be a trigger in the onset of anti-Ku autoimmunity via molecular mimicry between fungal proteins and the Ku autoantigen. Due to the low frequency of anti-Ku autoimmunity, multicentric collaboration is necessary to verify our hypothesis.
Guarneri
Fabrizio
F
Department of Territorial Social Medicine, Section of Dermatology, University of Messina, Messina, Italy. f.guarneri@tiscali.it
Guarneri
Biagio
B
Vaccaro
Mario
M
Guarneri
Claudio
C
D000595:Amino Acid Sequence; D034961:Antigens, Nuclear / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology*; D005656:Fungal Proteins / Q000276:immunology*; D006801:Humans; D000072200:Ku Autoantigen; D018716:Molecular Mimicry / Q000276:immunology; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000276:immunology*
D034961:Antigens, Nuclear; D001324:Autoantigens; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D014764:Viral Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen