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Abstract Number: 1601

The Presence Of IgG-Immune Complexes In The Cerebrospinal Fluids Is Associated With Central Neurocychiatric Manifestatin But Not With Intrathecal Production Of Proimmflammatory Cytokines/Chemokines Such as  Interferon-α In Systemic Lupus Erythematosus

Taku Yoshio1, Hiroshi Okamoto2, Kazuhiro Kurasawa3, Yoshiaki Dei4, Shunsei Hirohata5 and Seiji Minota6, 1Division of Rheumatology and Clinical Immunology, Jichi Medical University, School of Medicine, Shimotsuke-shi, Tochigi-ken, Japan, 2Minami-Otsuka Institute of Thechnology, Minami-Otsuka Clinic, Tokyo, Japan, 3Clinical Immunology, Dokkyo Medical University, Mibu-machi, Shimotsuga-gun, Tochigi-ken, Japan, 4Saiseikai Utsunomiya Hospital, Utsunomiya-shi, Tochigi-ken, Japan, 5Int Med/Rheumatol & Infec Dis, Kitasato University School of Medicine, Sagamihara, Japan, 6Division of Rheumatology and Clinical Immunology, Jichi Medical University, Shimotsuke,Tochigi, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: central nervous system involvement, IL-6, Interferons and systemic lupus erythematosus (SLE)

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Session Information

Session Title: Systemic Lupus Erythematosus - Clinical Aspects II: Central Nervous System Manifestations, Therapeutics

Session Type: Abstract Submissions (ACR)

Background/Purpose:  IgG-Immune complexes (IC) formed by CSF autoantibodies in patients with neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE) has reported to stimulate the production of interferon (IFN)-α, IL-8, IP-10, MCP-1 in a bioassay containing plasmacytoid dendritic cells and a source of antigens.The pathological roles of these cytokines/chemokines in the CSF has been reported in patients with NPSLE. These results suggest that IgG-IC in the CSF may have pathogenic roles in central NPSLE.

We investigated whether IgG-IC are present in the CSF of patients with central NPSLE and correlated with cytokines/chemokines such as IFN-a levels in the CSF.

Methods: 50 SLE patients, of whom the CSF samples were obtained, were enrolled. Of 50 SLE patients, 29 had central NPSLE and the reminder 21 did not have central NPSLE. The levels of IgG-IC in the CSF samples were measured by ELISA kits. The levels of IL-6, IL-8, IP-10, MCP-1, and G-CSF in the CSF samples were measured by Bio-Plex Pro Assays. IFN-α in the CSF samples were measured by ELISA kits. Antiribosomal P protein antibody (anti-P) titers in the CSF samples were measured by ELISA using recombinant ribosomal P0 protein as the antigen.

Results:   CSF IgG-IC levels in 29 patients with central NPSLE were significantly higher than in 21 patients without central NPSLE (mean ± SD, median [range]; 3.75 ± 4.80 μg/ml, 1.28 [0.09 – 18] vs. 1.01 ± 1.40 μg/ml, 0.49 [0.09 – 6.38]; p = 0.047). The CSF levels of IL-6, IL-8, IP-10, MCP-1, and G-CSF and CSF anti-P titers in 29 patients with central NPSLE were significantly higher than those in 21 patients without central NPSLE, respectively (275.1 ± 595.9 pg/ml, 17.4 [1.9 – 2882.2] vs. 11.6 ± 12.8 pg/ml, 5.0 [1.3 – 45.2]; p = 0.007, 482.5 ± 1697.6 pg/ml, 99.2 [17.7 – 9233.7] vs. 58.5 ± 81.2 pg/ml, 31.0 [6.3 – 366.8]; p = 0.004, 8988.0 ± 15406.2 pg/ml, 3248.2 [228.7 – 76941.5] vs. 2988.3 ± 4126.9 pg/ml, 1137.8 [427.6 – 15765.1]; p = 0.034, 555.7 ± 481.0 pg/ml, 387.6 [35.6 – 2008.5] vs. 284.3 ± 161.5 pg/ml, 265.1 [55.6 – 664.6]; p = 0.021, 71.5 ± 156.0 pg/ml, 33.4 [0.81 – 779.4] vs. 15.5 ± 24.8 pg/ml, 3.9 [0 – 102.7]; p = 0.009 and 6.90 ± 9.36 CSFU/ml, 2.6 [0 – 31.0] vs. 3.75 ± 9.25 CSFU/ml, 0.95 [0.14 – 41.3]; p = 0.021). Unexpectedly, CSF IFN-α levels in patients with central NPSLE were not significantly higher than in patients without central NPSLE (13.1 ± 58.9 pg/ml, 0 [0 – 314.0] vs. 0.17 ± 0.75 pg/ml, 0 [0 – 3.4]; p = 0.565). Discriminant analysis showed the most significant association between IgG-IC levels in the CSF and the presence of central NPSLE (P = 0.02). However, CSF IgG-IC levels in these patients were not significantly correlated with CSF levels of any of the studied cytokines/chemokines.  The significant positive association between CSF IgG-IC levels and CSF anti-P titers was not observed in these patients.

Conclusion:  The intrathecal IgG-IC might have important roles in the pathogenesis of central NPSLE. But the intrathecal IgG-IC was not associated with the intrathecal production of cytokines/chemokines studied in this study.


Disclosure:

T. Yoshio,
None;

H. Okamoto,
None;

K. Kurasawa,
None;

Y. Dei,
None;

S. Hirohata,
None;

S. Minota,
None.

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