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To clarify whether mouse monoclonal antibodies (mAb) against human thrombomodulin (TM), which react with human TM present on the endothelial cell (EC) surface, have anti–endothelial cell antibody (AECA) activity and influence antiinflammatory properties of human TM expressed on the EC surface in vitro.Three preparations of mouse mAb against human TM that react with different sites of the human TM epidermal growth factor–like domain were tested for their ability to 1) bind to ECs, 2) modulate cytokine secretion from ECs, EC adhesion molecule expression, and neutrophil adhesion to ECs, and 3) stimulate nuclear translocation of NF‐κB through the degradation of cytoplasmic IκB in ECs. Recombinant human interleukin‐1β (IL‐1β) was used as a positive control, and mouse IgG1 and mouse IgG2a were used as negative controls.The 3 preparations of mouse mAb against human TM that bind to unfixed EC monolayers enhanced IL‐6 and IL‐8 secretion from ECs, up‐regulated expression of endothelial leukocyte adhesion molecule 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 on EC monolayers, and enhanced neutrophil adhesion to ECs to a degree similar to that observed with IL‐1β stimulation, but they did not induce the secretion of tumor necrosis factor α or IL‐1β from ECs throughout the incubation period. The 3 preparations stimulated nuclear translocation of NF‐κB through the degradation of cytoplasmic IκB. Mouse IgG1 and mouse IgG2a did not exhibit such effects.These results suggest the possibility that AECA can react with antigens such as TM that are present on the EC surface and activate ECs. Such events on ECs may lead to vascular inflammation and damage in patients with connective tissue diseases and vasculitis in which AECA are present. [ABSTRACT FROM AUTHOR]

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. 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.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 published studies, only the sensitivity for psychosis and/or mood disorder was slightly improved, but it was still suboptimal (42% [95% CI 30–53%]); the specificity remained essentially the same (81% [95% CI 76–85%]).Anti‐P antibody testing has limited diagnostic value for NPSLE, and it is not helpful in differentiating among various disease phenotypes. [ABSTRACT FROM AUTHOR]