ANTIBODIES AGAINST A NOVEL NUCLEOLAR AND CYTOPLASMIC ANTIGEN (P105-P42) PRESENT IN THE SERA OF PATIENTS WITH A SUBSET OF RHEUMATOID-ARTHRITIS (RA) WITH SIGNS OF SCLERODERMA
M. Labrador et al., ANTIBODIES AGAINST A NOVEL NUCLEOLAR AND CYTOPLASMIC ANTIGEN (P105-P42) PRESENT IN THE SERA OF PATIENTS WITH A SUBSET OF RHEUMATOID-ARTHRITIS (RA) WITH SIGNS OF SCLERODERMA, Clinical and experimental immunology, 114(2), 1998, pp. 301-310
We identified three patients (two of them relatives) with RA and signs
of scleroderma whose sera contained a high titre of IgG class antibod
ies against the nucleoli and the nucleoplasm of cells of different mam
malian origins. Sera from these patients uniformly immunoprecipitated
four polypeptides, from a S-35-methionine-labelled HeLa cell extract,
whose mel. wts were 120, 105, 95 and 42 kD. Of these, the 95-kD protei
n was highly phosphorylated. By immunoblotting, these sera reacted wit
h 105-, 95- and 42-kD proteins and affinity-purified antibodies from t
hese, demonstrating that 105- and 95-kD proteins shared cross-reactive
epitopes. Moreover, affinity-purified antibodies from each of these p
roteins immunoprecipitated the whole complex. Localization studies usi
ng immunoelectron microscopy and in vivo actinomycin-D-treated cells d
emonstrated that the 105-, 95- and 42-KD proteins were present in the
granular component of the nucleolus and the nucleoplasm. In addition,
the 105- and 95-kD were present in free polyribosomes as well as ribos
omes attached to endoplasmic reticulum. Pulse/chase experiments strong
ly suggested that the complier was accomplished shortly after a 10-min
pulse. It was preferentially present in the nucleus after a 2 h chase
and in both nucleus and cytoplasm after a 5 h chase. We conclude that
a protein complex with a main nucleolar distribution is a new autoant
igen (p105-p42) recognized by autoantibodies present in the serum of a
subgroup of patients with RA and scleroderma signs. These antibodies
could be useful as diagnostic markers and as tools for further studies
involving the biology of the nucleolus.