Decreased Levels of CD54 (ICAM-1)-Positive Lymphocytes in the Peripheral Blood in Untreated Patients with Active Juvenile Dermatomyositis

Abstract

Significant abnormalities are observed in the peripheral blood of juvenile dermatomyositis (JDM) patients with active disease. In this study, we confirm that there is a significant increase in the relative percentage of B lymphocytes in the peripheral blood of a group of untreated children with newly diagnosed active JDM compared to healthy children (P < 0.0001). In order to investigate if properties intrinsic to B cells contributed to their relative increase in JDM, the percentage of B cells expressing activation markers (CD23, CD25, CD54, and CD69) was measured and compared to pediatric controls. Compared to healthy children less than 10 years of age (not significantly different from the JDM group), the JDM patients had an increase in the proportion of lymphocytes expressing CD19 (B cells; P ‫؍‬ 0.0017) and decreases in the percentage of lymphocytes that were CD3 ؊ CD16 ؉ and/or CD56 ؉ (NK cells; P ‫؍‬ 0.01) and CD3 ؉ CD8 ؉ (T suppressor/cytotoxic cells; P ‫؍‬ 0.02). There were no significant differences in any of the B-cell activation markers assessed. Of note, the percentage of CD54؉ non-B lymphocytes (i.e., T cells and NK cells expressing CD54) was significantly lower in the JDM patients (25% ؎ 5%) than in the "age-related" healthy control group (43% ؎ 4%; P ‫؍‬ 0.013). These results suggest the following for untreated children with active JDM: (i) the increase in the percentage of peripheral blood B cells is not due to intrinsic B-cell activation, and (ii) CD54/ICAM-1 ؉ non-B cells, CD8 ؉ T cells, and NK cells are being removed from circulation and may be participating in the pathophysiology of the disease.

Clinical manifestations and pathogenesis of hydroxyapatite crystal deposition in juvenile dermatomyositis

“…Our studies of untreated JDM lymphocytes documented depletion of killer cells (both NK and CD8 T cell) from the peripheral blood [28], which is compatible with reports that peripheral blood (PB) CD3+ T cells from patients with inflammatory myopathy are cytotoxic for myotubes [29]. The JDM PB CD8+CD3+ cells were also ICAM-1+ [30], and ICAM-1, which is an important adhesion molecule that facilitates several aspects of immune injury, is overexpressed in muscle from patients with inflammatory myopathies [31].…”

Increased Plasma Thrombospondin-1 (TSP-1) Levels Are Associated with the TNFα-308A Allele in Children with Juvenile Dermatomyositis

“…Narrowing of vessels can be attributed to vascular smooth muscle cell (VSMC) proliferation, with ensuing occlusion associated with adherent mononuclear leukocytes. In active JDM, ICAM-1-positive lymphocytes (primarily T cells; CD8 and CD56) are adherent to LFA-1 ϩ endothelial cells in the vascular lumen in blood vessels in muscle (unpublished results), with a concurrent decrease in these lymphocyte phenotypes in the peripheral blood (25). Upregulation of ICAM-1 on lymphocytes, coupled with VSMC proliferation, may play a pivotal role in perpetuating small vessel occlusion in JDM.…”

The inflammatory milieu in idiopathic inflammatory myositis

“…NK cell surface expression markers, such as CD161 (an NK T cell marker), suggest a role in disease pathogenesis [33]. In peripheral blood from JDM patients, the percentage of CD54 + non-B cells (ie, T cells and NK cells expressing CD54) is thought to be lower [34]. Additional evidence that NK cells may play a role in IIM comes from polymorphisms of the killer cell immunoglobulin-like receptors (KIR), a group of polymorphic receptors expressed on NK cells and subsets of T cells.…”