Objective. To quantitatively evaluate the diagnostic accuracy of antibodies to ribosomal P proteins (anti-P) for neuropsychiatric systemic lupus erythematosus (NPSLE) in general, for psychosis, mood disorder, or both, and for other diffuse manifestations.Methods. This international meta-analysis combined standardized data from 1,537 lupus patients contributed by 14 research teams. Weighted estimation of sensitivity and specificity with fixed-effects and random-effects models, as well as summary receiver operating characteristic (SROC) curve analysis, was used to summarize test performance. The robustness of the overall estimates was examined in sensitivity analyses that included additional studies published up to November 1, 2004 in the Medline, EMBase, and Cochrane databases.Results. Combining the data from the 14 teams, the weighted sensitivity and specificity estimates for the diagnosis of NPSLE were 26% (95% confidence interval [95% CI] 15-42%) and 80% (95% CI 74-85%), respectively. For psychosis, mood disorder, or both, the sensitivity and specificity were 27% (95% CI 14-47%) and 80% (95% CI 74-85%), respectively. For other diffuse manifestations, the sensitivity was 24% (95% CI 12-42%), and the specificity was 80% (95% CI 73-85%). The proportion of patients with anti-P antibodies did not vary markedly across different presentations of NPSLE. Between-study heterogeneity was substantial, but the SROC curves were consistent with the weighted estimates. In further analyses that included another 24

Objective. Newborns of mothers positive for antiRo/SSA autoantibodies may develop a series of electrocardiographic (EKG) disturbances. Prolongation of the corrected QT (QTc) interval was recently reported in a significant proportion of children with maternally acquired anti-Ro/SSA antibodies, with a concomitant disappearance of EKG abnormalities and acquired maternal autoantibodies during the first year, suggesting a direct, reversible electrophysiologic effect of anti-Ro/ SSA antibodies on the ventricular repolarization. On this basis, we investigated whether these antibodies may also affect cardiac repolarization in anti-Ro/SSApositive adult patients with connective tissue diseases.Methods. Fifty-seven patients with connective tissue diseases were selected: 31 had anti-Ro/SSA antibodies and 26 did not (controls). In all subjects, we analyzed the QTc interval, heart rate variability, and signalaveraged high-resolution EKG recording.Results. Anti-Ro/SSA-positive patients showed a significant prolongation of the mean QTc interval compared with the controls (mean ؎ SD 445 ؎ 21 versus 419 ؎ 17 msec; P ‫؍‬ 0.000005). Eighteen of the 31 anti-Ro/SSA-positive patients (58%) and none of the 26 anti-Ro/SSA-negative patients had QTc values above the upper limit of normal (440 msec). Both groups had a reduction in heart rate variability, with a prevalence for the sympathetic nervous system and a high incidence of ventricular late potentials; these values were not significantly different between the 2 groups.Conclusion. Adult patients with anti-Ro/SSApositive connective tissue diseases showed a high prevalence of QTc interval prolongation. This feature, with the concomitant abnormalities in the autonomic tone and ventricular late excitability observed in all patients studied, suggests that anti-Ro/SSA-positive patients may have a particularly high risk of developing lifethreatening arrhythmias.Neonatal lupus is a rare syndrome related to the transplacental passage of autoantibodies from mothers positive for anti-Ro/SSA (and anti-La/SSB) to their newborns. These mothers frequently have autoimmune disorders, especially connective tissue diseases; however, they are sometimes entirely asymptomatic. The main feature of neonatal lupus is congenital heart block (CHB), an irreversible disturbance in cardiac conduction. Many recent studies have investigated the possible electrophysiologic and molecular mechanisms of CHB, and the findings suggest a direct arrhythmogenic activity of anti-Ro/SSA antibodies. In particular, it has been demonstrated that affinity-purified anti-Ro/SSA antibodies from mothers of children with CHB are able to induce a complete atrioventricular block in the human fetal heart as well as in a rat model of the heart, which inhibits L-type calcium currents (1).CHB is the main, but not the only, electrocardiographic abnormality associated with the transplacental passage of anti-Ro/SSA antibodies. Mazel and colleagues (2) reported sinus bradycardia in a murine model injected with IgG obtained from mothers of childr...

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The objective of this study was to determine the HLA class II associations of the anticardiolipin (aCL) and anti-beta2GPI (abeta2GPI) antibodies in a large series of European patients with systemic lupus erythematosus (SLE). A cohort of 577 European SLE patients was enrolled. aCL and abeta2GPI were measured by ELISA methods. Molecular typing of HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1 loci was performed by the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method. aCL of IgG, IgM and IgA isotypes were detected in 22.8%, 14% and 13.9% of patients, respectively. IgG and IgM abeta2GPI were detected in 20% of patients. aCL showed positive association with HLA DRB1*04, DRB1*0402, DRB1*0403, DRB1*07, DRB3*0301, DQA1*0201, DQA1*0301, DQB1*0302, and negative association with DQA1*0501, DRB3*0202. abeta2GPI showed positive association with DRB1*0402, DRB1*0403, DQB1*0302. DRB1*0402 carried the highest relative risk for the presence of both aCL (RR=8. 1) and abeta2GPI (RR=4.6). Our results confirm the already described associations of aCL with HLA DR4 and DR7, but also demonstrate that, among the alleles at the DRB1*04 locus, the *0402 was most represented both in aCL and in abeta2GPI positive patients. In addition, HLA class II associations of abeta2GPI are for the first time extensively examined in a large cohort of European SLE patients.

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Objective. Recent evidence suggests that anti-Ro/SSA antibodies, strongly associated with the development of congenital heart block, may also be arrhythmogenic for the adult heart. In fact, anti-Ro/SSA-positive patients with connective tissue disease (CTD) frequently display corrected QT (QTc) prolongation associated with an increase in ventricular arrhythmias. However, QTc prolongation prevalence markedly differs throughout the studies (10 -60%), but the reason why is not yet clear. The aim of this study was to evaluate whether anti-Ro/SSA-associated QTc prolongation in adult patients with CTD is related to antibody level and specificity. Methods. Forty-nine adult patients with CTD underwent a resting 12-lead electrocardiogram recording to measure QTc interval, and a venous withdrawal to determine anti-Ro/SSA antibody level and specificity (anti-Ro/SSA 52 kd and anti-Ro/SSA 60 kd) by immunoenzymatic methods and Western blotting. Results. In our population, a direct correlation was demonstrated between anti-Ro/SSA 52-kd level and QTc duration (r ‫؍‬ 0.38, P ‫؍‬ 0.007), patients with a prolonged QTc had higher levels of anti-Ro/SSA 52 kd with respect to those with a normal QTc (P ‫؍‬ 0.003), and patients with a moderate to high level (>50 units/ml) of anti-Ro/SSA 52 kd showed a longer QTc interval (P ‫؍‬ 0.008) and a higher QTc prolongation prevalence (P ‫؍‬ 0.008) than those with a low positive/negative level (<50 units/ml). On the contrary, no association was found between QTc and anti-Ro/SSA 60-kd level. Conclusion. In anti-Ro/SSA-positive adult patients with CTD, the occurrence of QTc prolongation seems strictly dependent on the anti-Ro/SSA 52-kd level. This finding, possibly explaining the different QTc prolongation prevalence reported, strengthens the hypothesis that an extremely specific autoimmune cross-reaction is responsible for the antiRo/SSA-dependent interference on ventricular repolarization.

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