Serological cross-reactivity between a human Ro/SS-A autoantigen (calreticulin) and the lambda Ral-1 antigen of Onchocerca volvulus.
We have cloned and sequenced a 46-kD Ro/SS-A autoantigen gene that is the human homologue of the calcium-binding protein, calreticulin. The sequence of this 46-kD Ro/SS-A protein (calreticulin) has significant homology to lambda Ral-1, a recombinant cDNA clone corresponding to a major antigen of the nematode, Onchocerca volvulus, the infectious agent of onchocerciasis. We therefore sought to determine whether antibodies produced by onchocerciasis patients might crossreact with the human 46-kD Ro/SS-A autoantigen (calreticulin). 20 of 22 sera from Liberian onchocerciasis patients who had no known evidence of autoimmune disease were found to contain antibodies that reacted with the 46-kD Ro/SS-A (calreticulin) by immunoblot analysis. Characteristic of sera reactive with Ro/SS-A antigens, some onchocerciasis sera also immunoprecipitated the Ro/SS-A-associated hY RNAs. In addition, a monoclonal antibody raised against O. volvulus organisms reacted to purified human WiL-2 cell 46 kD Ro/SS-A antigen (calreticulin) by ELISA. These results strongly suggest that onchocerciasis patients produce antibodies that crossreact with the 46-kD human Ro/SS-A autoantigen (calreticulin) and raise the possibility that infectious organisms such as O. volvulus might play a triggering or exacerbating role in the human Ro/SS-A autoimmune response.
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Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235.
McCauliffe
D P
DP
Büttner
D W
DW
Lucius
R
R
Capra
J D
JD
Sontheimer
R D
RD
Lieu
T S
TS
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015152:Blotting, Northern; D002135:Calcium-Binding Proteins / Q000276:immunology*; D037282:Calreticulin; D002461:Cell Line, Transformed; D003429:Cross Reactions; D015801:Helminth Proteins / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D009854:Onchocerca / Q000276:immunology*; D009855:Onchocerciasis / Q000276:immunology; D011233:Precipitin Tests; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000099207:SS-A Antigen
D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D001324:Autoantigens; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D015801:Helminth Proteins; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C080575:RAL-1 protein, Onchocerca volvulus; C116006:RO60 protein, human