Autoantibodies to EEA1, an antigen on early endosomes, were first repo
rted in the serum of a patient with subacute cutaneous lupus erythemat
osus (SCLE). Here we have examined 38 sera selected for investigation
of autoantibodies to EEA1 on the basis of cytoplasmic vesicle-like rea
ctivity by immunofluorescence, Ten of the sera were reactive to a HeLa
cell protein of approximately the same M-r as human EEA1, Eight of th
ese sera belonged to the IgG(1) subclass. Five of the sera reacted wit
h fusion proteins incorporating either the amino (from amino acids 1 t
o 209) or the carboxyl (incorporating the most C-terminal 300 amino ac
ids) terminus of the human EEA1 protein, Antigens reactive with these
5 sera colocalized with internalized transferrin receptors, indicating
their association with early endosomes. The other 5 sera which did no
t react to both fusion proteins did not colocalize with internalized t
ransferrin receptors, We conclude that 5 of the 38 patients (13%) have
autoantibodies to EEA1. None of these patients have SCLE, but have ge
neralized joint pain, polyarthritis, rheumatoid arthritis, or circulat
ing rheumatoid factors. (C) 1998 Academic Press.