Antibody against chromatin assembly factor-1 is a novel autoantibody specifically recognized in systemic lupus erythematosus.
Autoantibodies to proliferating cell nuclear antigen (PCNA) are specifically, if rarely, present in systemic lupus erythematosus (SLE) patient sera. Even SLE patients lacking PCNA reactivity often show reaction to PCNA-binding protein. Here, immunoreactivity to chromatin assembly factor-1 (CAF-1), an essential molecule for DNA replication and a PCNA-binding protein, was compared for the sera of SLE patients, normal healthy controls (NHCs) and other disease controls, and in autoimmune sera reactive to standard autoantigens, by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence, and immunoblotting. CAF1 and IRF1 expression in SLE and NHC peripheral mononuclear cells were compared by quantitative real-time polymerase chain reaction. Serum interferon-γ-inducing protein-10 and anti-double-stranded (ds)DNA antibody levels were measured by ELISA. Increased CAF-1 autoimmune reactivity was recognized in SLE or serum anti-dsDNA antibody-positive patients. Significantly greater central nervous system (CNS) involvement (aseptic meningitis) and serum anti-dsDNA antibody titers were present more often in anti-CAF-1 antibody-positive than antibody-negative SLE patients. IFN-γ positively regulated CAF-1 expression in vitro and was associated with anti-CAF-1 antibody production in SLE. Thus, a novel anti-CAF-1 autoantibody is frequently found in patients with SLE and is a useful biomarker for diagnosis, especially in cases with CNS involvement. Aberrant IFN-γ regulation appears to play an important role in anti-CAF-1 antibody production in SLE.
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
K
K
Doe
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan k-nozawa@juntendo.ac.jp.
K
K
Nozawa
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
K
K
Hiruma
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Y
Y
Yamada
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Y
Y
Matsuki
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
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S
Nakano
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
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M
Ogasawara
Laboratory of Molecular and Biochemical Research, Research Support Center, Juntendo University Graduate School of Medicine, Chiba, Japan.
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H
Nakano
Laboratory of Molecular and Biochemical Research, Research Support Center, Juntendo University Graduate School of Medicine, Chiba, Japan.
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T
Ikeda
Laboratory of Molecular and Biochemical Research, Research Support Center, Juntendo University Graduate School of Medicine, Chiba, Japan.
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T
Ikegami
Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan.
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M
Fujishiro
Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan.
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M
Kawasaki
Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan Department of Internal Medicine and Rheumatology, Juntendo University Urayasu Hospital, Chiba, Japan.
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K
Ikeda
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
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H
Amano
Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan Department of Internal Medicine and Rheumatology, Juntendo University Urayasu Hospital, Chiba, Japan.
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S
Morimoto
Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan.
H
H
Ogawa
Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan.
K
K
Takamori
Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan Department of Internal Medicine and Rheumatology, Juntendo University Urayasu Hospital, Chiba, Japan.
I
I
Sekigawa
Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Y
Y
Takasaki
D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured; D056504:Chromatin Assembly Factor-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D055815:Young Adult
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D015415:Biomarkers; D056504:Chromatin Assembly Factor-1; D007371:Interferon-gamma
Autoantibody; autoantigen; chromatin assembly factor-1; systemic lupus erythematosus