Anti-endothelial cell antibodies are prevalent in juvenile idiopathic arthritis: implications for clinical disease course and pathogenesis.

To determine the prevalence of anti-endothelial cell antibodies (AECA) in children with juvenile idiopathic arthritis (JIA) versus healthy control children. Twenty-eight children with active JIA were studied (ten each with polyarticular and oligoarticular disease, and eight with systemic onset disease). AECA were determined by a cell-based ELISA from samples obtained every 3 months over a 2 year period in each subject. These levels were compared against previously determined levels of von Willebrand factor antigen, fibrin d-dimer, and soluble forms of ICAM-1 and E-selectin, as well as clinical measures of disease activity. AECA were detected in 5/10 oligoarticular, 6/10 polyarticular, and 7/8 systemic JIA subjects and 0/14 controls. Mean levels of AECA were significantly higher in subjects with oligoarticular, and especially systemic disease as compared to polyarticular and control groups when analyzed by ANOVA. AECA are prevalent in JIA and are present more often and at higher levels in systemic disease.

Pooled human gammaglobulin modulates surface molecule expression and induces apoptosis in human B cells.

We have previously shown that the pooled human gammaglobulin (IVIG) inhibited mixed lymphocyte reaction (MLR). In this study, we examined (1) if IVIG contains blocking antibodies reactive with cell surface molecules required for alloantigen recognition and (2) if IVIG modulates these surface molecule expressions using flow cytometry. IVIG does not contain significant amounts of blocking antibodies against CD3, CD4, CD8, CD20, CD14, CD40, MHC class I and class II. It reduces the number of intact B cells and monocytes, reduces or modulates CD19, CD20 and CD40 expression on B cells, and induces morphological changes in B cells. This B-cell modulation results primarily because of apoptosis. IVIG also induces apoptosis in T cells and monocytes, but to a lesser degree. Induction of apoptosis requires the intact IgG molecule. Reduction of intact B cell and monocyte cell numbers, modulation of surface molecule expression on B cells, and deletion of B and T cells by apoptosis could result in inhibition of optimal T-cell activation. This likely represents the primary mechanism responsible for IVIG suppression of the MLR, and may account for many of the observed beneficial effects of IVIG seen in the treatment of human autoimmune and alloimmune disorders.