Date: Monday, November 9, 2015
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Proliferating cell nuclear antigen (PCNA) is known to be an autoantigen specifically recognized in patients with SLE. PCNA constitutes PCNA-complex along with several PCNA-binding proteins in vivo. We have consecutively published that autoantibodies to PCNA-binding proteins are easily produced in SLE patients as well as autoantibody to PCNA itself. Furthermore, we have recently published the novel serum autoantibody to chromatine assembly factor-1(CAF-1), which belongs to the PCNA-binding proteins, might be an useful biomarker for neuropsychiatric (NP) SLE. Ribonuclease-H (RNase-H) also belongs to the PCNA-binding proteins and functions as a regulating factor for cell division in coordination with other PCNA-binding proteins such as CAF-1. Therefore, we assume that RNase-H will be a candidate of autoantigen specifically recognized in SLE and investigated the clinical association of anti-RNase-H antibody with SLE patients.
Patients sera consisting of SLE (n=57), PM/DM (n=40), SSc (n=39), SS (n=28), MCTD (n=28), RA (n=29), and normal healthy controls (NHCs) (n=73) were collected from serum bank of Juntendo University Hospital with their informed consent. Immunoreactivity against both RNase-H and CAF-1 recombinant antigens was evaluated by ELISA and was further confirmed by immunoblotting. The cut-off value designating a positive reaction in ELISA was defined as the mean value of NHCs +3 standard deviations.
Serum anti-RNase-H antibody was observed in 33% of SLE patients. The anti-RNase-H antibody was not recognized in both all control diseases and NHCs. Moreover, the coexistence of anti-RNase-H antibody and anti-U1 RNP antibody revealed high incidence of NPSLE. Moreover, titer of anti-RNase-H antibody was strongly correlated with titer of anti-CAF-1 antibody in regression analysis.
In the present study, we identified anti-RNase-H antibody as a novel autoantibody specifically recognized in SLE. Measurement of anti-RNase-H antibody can be used for the diagnosis of SLE. Moreover, it might be a useful biomarker for NPSLE when anti-U1 RNP antibody coexists. The strong correlation in titer of anti-RNase-H and CAF-1 antibodies suggested that a breakdown of immune tolerance against component proteins of PCNA-complex lead to elicit autoimmune response to the other components of PCNA-binding proteins. This phenomenon is considered as epitope spreading which plays important role for the autoantibody production in SLE.
To cite this abstract in AMA style:Nozawa K, Doe K, Hiruma K, Yamada Y, Takasaki Y. Antibody Against Ribonuclease-H Is a Novel Autoantibody Specifically Recognized in Systemic Lupus Erhythematosus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/antibody-against-ribonuclease-h-is-a-novel-autoantibody-specifically-recognized-in-systemic-lupus-erhythematosus/. Accessed October 21, 2017.
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