Background Systemic lupus erythematosus (SLE) is characterized by multi-organ involvement and the production of autoantibodies directed against several nuclear proteins, among which the most specific are anti-Sm, anti-dsDNA and anti-ribosomal P protein (Rib-P) . Yet anti-Rib-P is not part of the SLE classification criteria .
Objectives We aimed to evaluate the diagnostic performance of anti-Rib-P in comparison to anti-Sm and anti-dsDNA antibodies in SLE patients and also to identify its association with clinical manifestations.
Methods In a cross-sectional evaluation we included 127 SLE patients, 100 healthy controls and 256 rheumatic disease controls (100 Rheumatoid Arthritis, 99 Ankylosing Spondylitis, 34 Juvenile Idiopathic Arthritis and 23 Psoriatic Arthritis).
We have used EliA™ Rib-P, EliA™ Sm and EliA™ DNA, from Phadia®, to simultaneously determine autoantibodies titers. Receiver operating characteristic (ROC) curves were performed and the cut-off values of positivity determined. The relationship between demographic parameters, clinical features, and the autoantibodies titers was assessed by univariable followed by multivariable linear regression analyses.
Results The cut-off values of positivity were 4.45 U/ml, 3.4 U/ml and 15.0 U/ml for anti-Rib-P, anti-Sm and anti-dsDNA, respectively.
Anti-Rib-P autoantibodies were positive in 14.2% of the SLE patients (mean concentration of 4.9±20.2 U/ml), in 0.8% of the rheumatic diseases control group (2 RA patients) and in none of the healthy controls. Anti-Sm antibodies were positive in 9.4% (mean concentration 2.8±13.8 U/ml) and anti-dsDNA autoantibodies in 49.6% of the SLE patients (mean concentration 44.6±73.8 U/ml). There was no positivity for anti-Sm in groups other than SLE, while anti-dsDNA was found in 6 (6%) healthy control subjects and in 5 (2%) patients with other rheumatic diseases.
The tests performance was evaluated and the outcome was as follows (PPV – Positive Predictive Value; NPV – Negative Predictive Value):
– Anti-Rib-P: sensitivity = 14.2%; specificity = 99.4%; PPV = 90.0%; NPV = 76.4%
– Anti-Sm: sensitivity = 9.4%; specificity = 100%; PPV = 100%; NPV = 75.6%
– Anti-dsDNA: sensitivity = 49.6%; specificity = 96.9%; PPV = 85.1%; NPV = 84.4%
Among the 18 anti-Rib-P positive samples, 12 were also positive for anti-dsDNA, 2 were positive for the three autoantibodies, and 4 tested positively only for anti-Rib-P antibodies.
In multivariable analysis Caucasian ethnicity was negatively associated with anti-Rib-P antibody titers (β=-0.190, p=0.034); serositis positively associated with anti-Sm titers; anti-dsDNA autoantibodies titers were related to a more active lupus (higher SLEDAI2K and renal involvement) and to shorter disease duration. No relationship was found between anti-Rib-P antibodies titers and neuropsychiatric manifestations as defined by SLE classification criteria.
Conclusions Anti-Rib-P autoantibodies determination should be considered for inclusion in the SLE classification criteria as it is highly specific and has a good predictive diagnostic value.
Mahler M, Kessenbrock K, Szmyrka M, Takasaki Y, Garcia-De La Torre I, Shoenfeld Y et al.: International multicenter evaluation of autoantibodies to ribosomal P proteins. Clin Vaccine Immunol 2006, 13: 77-83.
Toubi E, Shoenfeld Y: Clinical and biological aspects of anti-P-ribosomal protein autoantibodies [Review]. Autoimmun Rev 2007, 6: 119-125.
Disclosure of Interest D. Carmona-Fernandes Grant/Research support from: Phadia, M. J. Santos Grant/Research support from: Phadia, J. E. Fonseca Grant/Research support from: Phadia