PML nuclear body component Sp140 is a novel autoantigen in primary biliary cirrhosis.
OBJECTIVE
Some patients with primary biliary cirrhosis (PBC) have antinuclear antibodies (ANAs). These ANAs include the "multiple nuclear dots" (MND) staining pattern, targeting promyelocytic leukemia protein (PML) nuclear body (NB) components, such as "speckled 100-kD" protein (Sp100) and PML. A new PML NB protein, designated as Sp140, was identified using serum from a PBC patient. The aim of this study was to analyze the immune response against Sp140 protein in PBC patients.


METHODS
We studied 135 PBC patients and 157 pathological controls with type 1 autoimmune hepatitis, primary sclerosing cholangitis, and systemic lupus erythematosus. We used indirect immunofluorescence and a neuroblastoma cell line expressing Sp140 for detecting anti-Sp140 antibodies, and a commercially available immunoblot for detecting anti-Sp100 and anti-PML antibodies.


RESULTS
Anti-Sp140 antibodies were present in 20 (15%) PBC patients but not in control samples, with a higher frequency in antimitochondrial antibody (AMA)-negative cases (53 vs. 9%, P<0.0001). Anti-Sp140 antibodies were found together with anti-Sp100 antibodies in all but one case (19 of 20, 90%) and with anti-PML antibodies in 12 (60%) cases. Anti-Sp140 positivity was not associated with a specific clinical feature of PBC.


CONCLUSIONS
Our study identifies Sp140 as a new, highly specific autoantigen in PBC for the first time. The very frequent coexistence of anti-Sp140, anti-Sp100 and anti-PML antibodies suggests that the NB is a multiantigenic complex in PBC and enhances the diagnostic significance of these reactivities, which are particularly useful in AMA-negative cases.
Dipartimento di Medicina Clinica, Alma Mater Studiorum University of Bologna, Italy. alessandro.granito@unibo.it
Alessandro
A
Granito
Wei-Hong
WH
Yang
Luigi
L
Muratori
Mark J
MJ
Lim
Ayako
A
Nakajima
Silvia
S
Ferri
Georgios
G
Pappas
Chiara
C
Quarneti
Francesco B
FB
Bianchi
Donald B
DB
Bloch
Paolo
P
Muratori
D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D034961:Antigens, Nuclear / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015209:Cholangitis, Sclerosing / Q000276:immunology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D019693:Hepatitis, Autoimmune / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D007558:Italy; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000097:blood / Q000276:immunology*
D000974:Antibodies, Antinuclear; D034961:Antigens, Nuclear; D001324:Autoantigens; C102470:SP140 protein, human; D014157:Transcription Factors