Heterogeneous nuclear ribonucleoprotein h1, a novel nuclear autoantigen.
BACKGROUND
Serum samples from patients with autoimmune connective tissue diseases that show a finely speckled antinuclear antibody (ANA) on indirect immune-fluorescence often have antibodies against unknown nuclear target antigens. To search for such autoantigens we applied a proteomic approach using sera from patients with a high ANA titer (>or=640) and finely speckled fluorescence but in whom no antibodies to extractable nuclear antigens (ENA) could be identified.


METHODS
Using an immunoproteomics approach we identified heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) as a novel nuclear target of autoantibody response.


RESULTS
Recombinant rat hnRNP H1 reacted in Western blot analyses with 48% of 93 sera from patients with primary Sjögren syndrome and with 5.2% of 153 sera from patients with other connective tissue diseases (diseased controls). For comparison, the diagnostic sensitivity and specificity of anti-Sjögren syndrome A (SSA) antibodies for primary Sjögren syndrome in the same patient cohort were 88.2% and 76.3%, respectively. Interestingly, 5 of 11 primary Sjögren syndrome patients with no anti-SSA or anti-SSB antibodies had anti-hnRNP H1 antibodies. Anti-hnRNP H1 antibodies were preabsorbed by hnRNP H1, as demonstrated by indirect immunofluorescence. In an evaluation of the presence of anti-hnRNP H1 antibodies in 188 consecutive samples submitted to the clinical laboratory with positive ANA (titer >or=160), anti-hnRNP H1 antibodies were found in 3 of 7 (2 primary and 5 secondary) Sjögren syndrome patients and in 8.3% of the diseased controls.


CONCLUSIONS
HnRNP H1 is a newly discovered autoantigen that could become an additional diagnostic marker.
Van den Bergh
Karolien
K
Laboratory Medicine, Immunology, University Hospitals Leuven, Leuven, Belgium.
Hooijkaas
Herbert
H
Blockmans
Daniel
D
Westhovens
René
R
Op De Beéck
Katrijn
K
Verschueren
Patrick
P
Dufour
Diana
D
van de Merwe
Joop P
JP
Fijak
Monika
M
Klug
Jörg
J
Michiels
Georges
G
Devogelaere
Benoit
B
De Smedt
Humbert
H
Derua
Rita
R
Waelkens
Etienne
E
Blanckaert
Norbert
N
Bossuyt
Xavier
X
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015153:Blotting, Western; D015331:Cohort Studies; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000097:blood / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
D001323:Autoantibodies; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D011994:Recombinant Proteins