Antibody against chromatin assembly factor-1 is a novel autoantibody specifically recognized in systemic lupus erythematosus

Abstract

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.

Interferon-Inducible Protein 10 and Disease Activity in Systemic Lupus Erythematosus and Lupus Nephritis: A Systematic Review and Meta-Analysis

“…We evaluated these 33 publications in detail. We found that 23 publications fulfilled the eligibility criteria (3006 patients; Figure 1) [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35]. While all studies investigated SLE patients, only 6 of them focused on LN [13,19,22,25,27,31].…”

“…The majority of the studies were conducted in Asia (11 studies), while others were from Europe, northern America, and Africa (eight, two, and two studies, respectively). There were 15 cross-sectional studies [14,17,19,21,22,23,24,26,27,29,31,32,33,34,35] and eight prospective cohort studies [13,15,16,18,20,25,28,30]. All studies were conducted in adults except for one study which was done in children with juvenile-onset SLE [19].…”

“…Multiple pairs of comparisons were available. Ten studies compared active SLE with inactive SLE [15,16,17,19,20,21,25,28,30,31] while 19 studies provided comparison between active SLE with healthy controls or other groups that were non-SLE patients [13,14,16,17,19,20,21,22,23,24,26,27,29,30,31,32,33,34,35]. Patients with active LN were compared with either active SLE without renal involvement (eight studies) [14,17,20,25,27,28,31,32], inactive SLE (nine studies) [13,14,17,19,20,21,25,28,31], non-SLE controls (10 studies) [13,14,17,19,20,21,22,28,31,32], or LN of other classes (two studies) [13,22].…”

“…Patients with active LN were compared with either active SLE without renal involvement (eight studies) [14,17,20,25,27,28,31,32], inactive SLE (nine studies) [13,14,17,19,20,21,25,28,31], non-SLE controls (10 studies) [13,14,17,19,20,21,22,28,31,32], or LN of other classes (two studies) [13,22]. The unit of measurement for serum IP-10 concentration was uniform in pg/mL except for two studies, which reported the level of serum IP-10 in ng/mL [29] or chemiluminescence intensity [33]. On the other hand, the measurement units for urine IP-10 were diversified including pg/mgCr, pg/mgCr x 100, mg/gCr × 10 5 , pg/mL, and pg/dL.…”

“…There were two studies that compared the presence of serum IP-10 in patients with SLE and non-SLE patients with other connective tissue diseases (19 rheumatoid arthritis, 21 systemic sclerosis, and 28 polymyositis/dermatomyositis). The serum IP-10 in SLE patients was significantly higher than rheumatoid arthritis patients [17] but was not significantly higher than systemic sclerosis and polymyositis/dermatomyositis patients [29].…”