Anti-U1 RNP antibodies in cerebrospinal fluid are associated with central neuropsychiatric manifestations in systemic lupus erythematosus and mixed connective tissue disease.
OBJECTIVE
To determine the significance of anti-U1 RNP antibodies in the cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD) who have central neuropsychiatric SLE (NPSLE).


METHODS
The frequency of antinuclear antibodies including anti-U1 RNP antibodies in the sera and CSF of 24 patients with SLE and 4 patients with MCTD, all of whom had neuropsychiatric syndromes, was determined using an RNA immunoprecipitation assay and an enzyme-linked immunosorbent assay. The frequency of anti-U1 RNP antibodies in the CSF of patients with central NPSLE was examined, and the anti-U1 RNP index ([CSF anti-U1 RNP antibodies/serum anti-U1 RNP antibodies]/[CSF IgG/serum IgG]) was compared with CSF interleukin-6 (IL-6) levels and the albumin quotient (Qalb, an indicator of blood-brain barrier damage). CSF and serum antibodies against U1-70K, U1-A, and U1-C, including autoantigenic regions, were examined, and the U1-70K, U1-A, and U1-C indices as well as the anti-U1 RNP index were calculated.


RESULTS
CSF anti-U1 RNP antibodies with an increased anti-U1 RNP index showed 64.3% sensitivity and 92.9% specificity for central NPSLE. The anti-U1 RNP index did not correlate with CSF IL-6 levels or the Qalb. The anti-U1-70K index was higher than the anti-U1-A and anti-U1-C indices in the CSF of anti-U1 RNP antibody-positive patients with central NPSLE. The major autoantigenic region for CSF anti-U1-70K antibodies appeared to be localized in U1-70K amino acid 141-164 residue within the RNA-binding domain.


CONCLUSIONS
The frequency of anti-U1 RNP antibodies in the CSF and the anti-U1 RNP index are useful indicators of central NPSLE in anti-U1 RNP antibody-positive patients. The predominance of anti-U1-70K antibodies in CSF suggests intrathecal anti-U1 RNP antibody production.
Sato
Takeshi
T
Kyoto University and National Hospital Organization Utano Hospital, Kyoto, Japan.
Fujii
Takao
T
Yokoyama
Tomoko
T
Fujita
Yoshimasa
Y
Imura
Yoshitaka
Y
Yukawa
Naoichiro
N
Kawabata
Daisuke
D
Nojima
Takaki
T
Ohmura
Koichiro
K
Usui
Takashi
T
Mimori
Tsuneyo
T
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D020945:Lupus Vasculitis, Central Nervous System / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000134:cerebrospinal fluid*; D012189:Retrospective Studies; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000134:cerebrospinal fluid / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear
D000888:Antibodies, Anti-Idiotypic; D015415:Biomarkers; D015850:Interleukin-6; D017412:Ribonucleoprotein, U1 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C490688:SNRNP70 protein, human; C491260:SNRPC protein, human; C075339:U1A protein