ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2522

Novel Autoantibody Against CAF-1 Is a Biomarker For CNS Manifestation in patients With SLE

Kentaro Doe1, Kazuhisa Nozawa2, Kaori Hiruma2, Yusuke Yamada1, Yuko Matsuki1, Soichiro Nakano1, Michihiro Ogasawara3 and Yoshinari Takasaki4, 1Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan, 2Rheumatology, Juntendo University School of Medicine, Tokyo, Japan, 3Department of internal medicine and rheumatology, Juntendo University School of Medicine, Tokyo, Japan, 4Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Systemic Lupus Erythematosus-Clinical Aspects III: Biomarkers, Quality of Life and Disease Indicators, Late Complications

Session Type: Abstract Submissions (ACR)

Background/Purpose: Proliferating cell nuclear antigen (PCNA) is known to be an autoantigen specifically recognized by antibodies in sera from patients with systemic lupus erythematosus (SLE).  Although a prevalence of anti-PCNA antibody among the patients with SLE is relatively rare (less than 5%), we have demonstrated that patients with SLE often elicit autoimmune response against multiple proteins consisting of PCNA complex even though immune response against PCNA itself is absent. Therefore, the autoimmune response to the consisting proteins of PCNA complex is a unique mechanism of autoantibody production specifically recognized in SLE. Chromatine assembly factor-1(CAF-1) is an essential molecule for DNA replication belonging to the constitutive proteins of PCNA complex. Therefore, we conducted this study to confirm whether the autoimmune response to CAF-1 occurred in patients with SLE.

Methods: Immunoreactivity against CAF-1 among sera with SLE, normal healthy controls (NHCs), and other disease controls (PM/DM, SSc, SjS, MCTD, and RA) was evaluated by ELISA and immunoblotting. The gene expression of CAF-1, interferon regulating factor-1 (IRF-1), and pro-apoptotic molecules (Fas, BID, and TNFRS10B) were measured by quantitative RT-PCR in peripheral mononuclear cells (PBMCs) of SLE patient in comparison with those of NHCs. Serum level of interferon gamma inducing protein-10 (IP-10) was measured by ELISA.

Results: Increased autoimmune response to CAF-1 was significantly observed in SLE compared to the disease controls and NHCs. CNS involvement and disease onset of younger age were significantly recognized in the anti-CAF-1 antibody positive lupus patients in comparison with those of anti-CAF-1 antibody negative lupus patients. In addition, increased gene expression of CAF-1 and proapoptotic molecules on PBMCs was observed in SLE compared to those of NHCs. Moreover, increased gene expression of IRF-1 in PBMCs along with serum level of IP-10 was significantly observed in SLE.

Conclusion: In the present study, we identified anti-CAF-1 antibody as a novel autoantibody specifically recognized in patients with SLE. Measurement of anti-CAF-1 antibody is useful for the diagnosis of SLE and could be a new biomarker for CNS lupus. Moreover, our results indicated that increased apoptosis and aberrant regulation of IFN-g in peripheral mononuclear cells (PBMCs) played an important role for a mechanism for anti-CAF-1 antibody production in SLE.

Disclosure:

K. Doe,
None;

K. Nozawa,
None;

K. Hiruma,
None;

Y. Yamada,
None;

Y. Matsuki,
None;

S. Nakano,
None;

M. Ogasawara,
None;

Y. Takasaki,
None.

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