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Antiribosomal P Protein Antibodies in Cerebrospinal Fluid Are Associated with Neuropsychiatric Systemic Lupus Erythematosus

TAKU YOSHIO, DAISUKE HIRATA, KOICHI ONDA, HIROYUKI NARA, and SEIJI MINOTA

ABSTRACT.

Objective.
To investigate whether antiribosomal P protein antibodies (anti-P) are present in the cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus (SLE), and if presence of anti-P in CSF is more strongly related to the appearance of neuropsychiatric SLE (NPSLE) than anti-P in serum.

Methods. CSF and serum samples from 70 patients with SLE were used. Patients were divided into 4 groups: 21 patients with neurologic syndromes of the central nervous system (CNS); 19 patients with diffuse psychiatric/neuropsychological syndromes; 10 patients with complex presentations (neurologic syndromes of the CNS plus diffuse psychiatric/neuropsychological syndromes); and 20 patients without NPSLE based on diagnostic criteria for 19 NPSLE syndromes proposed by the American College of Rheumatology. IgG anti-P in CSF and serum samples were detected by Western blotting using rat liver ribosomes. Inhibition assay was performed using 5 anti-P-positive CSF samples preincubated with synthetic ribosomal P peptide. Western blotting results were compared with those from ELISA with synthetic ribosomal P peptide as antigen. The association of CSF and serum anti-P with NPSLE was analyzed.

Results. CSF and serum IgG anti-P by Western blotting were detected, respectively, in 20 (28.6%) and 32 (45.7%) of 70 patients. The presence of IgG anti-P by Western blotting in the CSF was supported by positive results in the inhibition assay and significant association with CSF IgG anti-P titers by ELISA. The frequency of CSF anti-P by Western blotting in SLE patients with serum anti-P was significantly higher than in SLE patients without serum anti-P (18/32 vs 2/38; p < 0.001). The frequency of CSF anti-P by Western blotting in patients with NPSLE was significantly higher than in patients without NPSLE (19/50 vs 1/20; p < 0.01). The frequency of CSF anti-P by Western blotting in the group with complex presentations (10/10) was significantly higher than in the other 3 groups [neurologic syndromes of CNS (5/21); diffuse psychiatric/neuropsychological syndromes (4/19); and patients without NPSLE (1/20)] (p < 0.001). The frequency of serum anti-P by Western blotting in patients with NPSLE was not significantly higher than in patients without NPSLE (25/50 vs 7/20; p = 0.192).

Conclusion. These results suggest that the presence of IgG anti-P in CSF of SLE patients may be involved in the appearance of NPSLE, especially in complex presentations. Measurement of IgG anti-P in CSF by Western blotting may be more useful for diagnosis of NPSLE than measurements in serum. (J Rheumatol 2005;32:34-9)

Key Indexing Terms:

ANTIRIBOSOMAL P PROTEIN ANTIBODIES
SYSTEMIC LUPUS ERYTHEMATOSUS
CEREBROSPINAL FLUID
NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS
NEUROLOGIC SYNDROMES OF THE CENTRAL NERVOUS SYSTEM
DIFFUSE PSYCHIATRIC/NEUROPSYCHOLOGICAL SYNDROMES


From the Division of Rheumatology and Clinical Immunology and Department of Psychiatry, Jichi Medical School, Tochigi, Japan.

Supported by a grant from the Ministry of Education, Science and Culture, Japan.

T. Yoshio, MD, Associate Professor; D. Hirata, MD, Assistant Professor Division of Rheumatology and Clinical Immunology; K. Onda, MD, Assistant, Department of Psychiatry; H. Nara, MD, Assistant; S. Minota, MD, Professor Division of Rheumatology and Clinical Immunology.

Address reprint requests to Dr. T. Yoshio, Division of Rheumatology and Clinical Immunology, Jichi Medical School, 3311 Yakushiji, Minamikawachi-machi, Tochigi-ken, 329-0498, Japan. E-mail: takuyosh@jichi.ac.jp

Submitted February 20, 2004; revision accepted August 27, 2004.




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