CYTOKINE-MEDIATED BONE-RESORPTION IN PATIENTS WITH THE HYPERIMMUNOGLOBULIN-E SYNDROME

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disor der characterized by increased serum immunoglobulin E levels. Bone fra gility is part of this syndrome, which has recently been reported to b e also associated with an imbalance in cytokine-secreting lymphocyte s ubpopulation. It has recently been shown that some cytokines can play a role in the bone fragility following menopause. We therefore investi gated six patients (mean age 16.5 +/- 8.5 years) affected by this rare syndrome in order to study their bone remodeling and the possible inv olvement of cytokines in causing the bone fragility associated with th is disease. Three of six patients had suffered long bone fractures; in four of six patients the cortical bone mass measured at the distal ra dius was two standard deviations below that of the aged-matched contro ls. Urinary pyridinoline excretion, a marker of bone resorption, was m arkedly increased in the two youngest patients. Adherent mononuclear c ells derived from these patients were cultured in vitro and the bone r esorbing activity (BRA) of the culture supernatant was measured by mea ns of a fetal rat long bone assay. The BRA was up to 28% above the bas al value. We compared the BRA and the cytokine production by the monon uclear cells of these patients to that of postmenopausal women. The BR A, and the IL1 beta, IL6, and TNF alpha levels in the mononuclear cell culture supernatants were identical for both HIES and postmenopausal women. However, the levels of PGE2 were higher and the levels of inter feron-gamma were lower in the HIES patients. In conclusion, increased bone resorption in young patients with the HIES is responsible for the cortical bone loss that leads to a higher incidence of fractures. The high BRA secreted by the mononuclear cells of these patients is simil ar to that found in mononuclear cells from postmenopausal women. These data provide evidence of potent mononuclear cell activation leading t o bone loss in HIES, which could be related to IgE-dependent mechanism s. (C) 1995 Academic Press, Inc.