Diagnostic value and clinical laboratory associations of antibodies against recombinant ribosomal P0, P1 and P2 proteins and their native heterocomplex in a Caucasian cohort with systemic lupus erythematosus

Abstract

IntroductionIn this study, we sought to determine the diagnostic value and clinical laboratory associations of autoantibodies against recombinant ribosomal P0, P1 and P2 proteins and their native heterocomplex in systemic lupus erythematosus (SLE).MethodsAutoantibodies against recombinant ribosomal P proteins (aRibPR0, aRibPR1 and aRibPR2) and antibodies against native ribosomal P heterocomplex (aRibPNH) were determined in sera from patients with SLE (n = 163), systemic sclerosis (n = 66), Sjögren's syndrome (n = 54), rheumatoid arthritis (n = 90) and healthy donors (n = 100) using enzyme-linked immunosorbent assay. Test results were correlated to medical records, including the American College of Rheumatology criteria, the Systemic Lupus Erythematosus Disease Activity Index 2000, laboratory data and medications of all SLE patients.ResultsSensitivities of 22.0% for aRibPR0, 14.9% for aRibPR2, 14.3% for aRibPNH and 10.7% for aRibPR1 were obtained at a specificity of 99%. The assay for aRibPR0 detection demonstrated the best performance in receiver-operating characteristics analysis, with aRibPR0 detectable in 10% of anti-Smith antibody and anti-double-stranded DNA-negative sera at a specificity of 100%. ARibPR0 positivity was associated with lymphocytopenia. ARibPR1+ patients had significantly higher γ-glutamyl transpeptidase (GGT) levels than their aRibPR1- counterparts. No specific damage occurred in aRibP+ lupus patients compared with a group of age-, sex- and nephritis-matched aRibP- lupus patients within 3 years.ConclusionsThe determination of antibodies against ribosomal P proteins improves the diagnosis of SLE and should therefore be implemented in upcoming criteria for the diagnosis or classification of SLE. High titers of aRibPR0 can be associated with lymphocytopenia, and high titers of aRibPR1 can be associated with elevated GGT levels. So far, there is no evidence for a prognostic value of aRibPs for damage.

Significance of Antibodies Against the Native Ribosomal P Protein Complex and Recombinant P0, P1, and P2 Proteins in the Diagnosis of Chinese Patients with Systemic Lupus Erythematosus

“…Another finding of this study was that the frequency of reduced lymphocyte levels was significantly elevated in anti‐Rib‐P0 positive SLE patients. This association has been reported before and is in line with studies classifying anti‐Rib‐P as subtypes of antilymphocyte antibodies leading to penetration, apoptosis, and depletion of T cells .…”

“…The hit rate provided by anti‐dsDNA and anti‐Sm (72.7%) was increased by 4.6% upon additional testing for anti‐Rib‐P C , and by 7.6% upon additional testing for anti‐Rib‐P0/P1/P2. Together with similar findings by other studies , this substantiates the relevance of anti‐Rib‐P serology in suspected cases of SLE.…”

“…These values are in accordance with previous studies reporting anti‐Rib‐P positivity in 28–42% of Asian SLE patients, but slightly higher than shown for European, African, or American populations (6–35%) . Interestingly, Barkhudarova et al found prevalence rates of 14.3% (anti‐Rib‐P C ), 22.0% (anti‐Rib‐P0), 10.7% (anti‐Rib‐P1), and 14.9% (anti‐Rib‐P2) among 163 German SLE patients at 99% specificity, employing the same setup as in the present study . Thus, ethnicity‐based differences between patient cohorts are likely to account for the divergence of prevalence data.…”

“…Noteworthy, a recent multicenter evaluation reported a relationship between anti-Rib-P (C22) and SLEDAI scores only for a subgroup of participants and concluded that this serological parameter is likely not appropriate for measuring global disease activity (14). Considering that there are other reports substantiating or refuting this association (10)(11)(12)(13)15,36), further prospective large-scale studies may clarify this issue.…”

Autoantibodies, complement and type I interferon as biomarkers for personalized medicine in SLE

“…12,13 The most commonly used marker autoantibodies in SLE react with dsDNA, Smith (Sm) antigen, nucleosomes and ribosomal P proteins. 14,15 Antinucleosome antibodies occur in SLE at a frequency of 60%-100 %. 16 The frequency range may be influenced by factors like ethnicity, disease duration, disease activity and treatment.…”