Identification of autoantigens in psoriatic plaques using expression cloning.
To search for autoantigens in psoriatic plaques, we screened cDNA libraries of plaque epidermis with psoriatic serum samples. This approach has been highly successful in identifying tumor antigens, but has not been widely applied to autoimmune disease. We identified 11 autoantigens including three with prominent reactivity and plausible disease relevance. These are keratin 13 (K13), heterogeneous nuclear ribonucleoprotein-A1 (hnRNP-A1), and a previously uncharacterized protein, FLJ00294. Serum antibody screening for these demonstrated reactivity in 40%, 38%, and 27% of psoriasis patients, respectively. Most positive samples reacted with all three, and we found that this was due to cross-reactivity among them. Enzyme-linked immunospot assay (ELISPOT) analysis of psoriatic peripheral blood T cells confirmed that these autoantigens are also recognized by T cells. This demonstrates that this is a feasible method to identify autoantigens in an autoimmune target tissue, and suggests that these antigens warrant further study in psoriasis. Furthermore, but peripheral blood of normal controls reacted to these autoantigens with essentially the same frequencies as patients, suggesting that psoriatics may have not only an immune system which is capable of reacting to certain autoantigens, but also to a skin immunoregulatory alteration which allows this normal reactivity to develop into abnormal inflammation.
Jones
David A
DA
Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. dajones@partners.org
Yawalkar
Nikhil
N
Suh
Ki-Young
KY
Sadat
Sara
S
Rich
Benjamin
B
Kupper
Thomas S
TS
D001324:Autoantigens / Q000097:blood / Q000235:genetics*; D003429:Cross Reactions; D015723:Gene Library; D005820:Genetic Testing; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics; D006801:Humans; D007633:Keratins / Q000235:genetics; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology*
D001324:Autoantigens; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C000619656:hnRNPA1 protein, human; D007633:Keratins