We report the beneficial effects of calcium infusions in a child with hereditary resistance to 1,25(OH)2D and alopecia. This patient after transient responsiveness to vitamin D derivatives became unresponsive to all therapy despite serum 1,25(OH)2D concentrations maintained at levels -100-fold normal. A 7-mo trial with calcium infusions led to correction of biochemical abnormalities and healing of rickets. Bone biopsies (n = 3) showed a normal mineralization and the disappearance of the osteomalacia. Cultures of bone-derived cells demonstrated a lack of activation of 25-hydroxyvitamin D 24-hydroxylase and osteocalcin synthesis by 1,25(0H)2D3 (10-' and 10' M). These results demonstrate that (a) even in the absence of a normal 1,25(OH)2D3 receptor-effector system in bone cells, normal mineralization can be achieved in humans if adequate serum calcium and phosphorus concentrations are maintained; and (b) calcium infusions may be an efficient alternative for the management of patients with this condition who are unresponsive to large doses of vitamin D derivatives.
Costimulation of anti-CD3-triggered proliferative T-cell responses by type I and type IV collagen and fibronectin was studied in 25 patients with psoriasis and 12 healthy subjects. The stimulation index of anti-CD3-mediated responses in the presence of type I collagen was about half that in the controls. Although the CD3-dependent proliferative response of psoriatic lymphocytes in patients with active widespread plaque psoriasis was reduced by about 50%, costimulatory responses induced by type IV collagen and fibronectin were found to be enhanced in relation to the controls. The degree of costimulation by type IV collagen and fibronectin was related to disease severity. The highest values of the stimulation index were found in patients with a PASI greater than 24, skin involvement of more than 40% of body surface area, and a duration of psoriatic lesions of more than 3 months. The results indicated that in active widespread plaque psoriasis subpopulations of T cells bearing receptors for some extracellular matrix proteins were increased in the peripheral blood. A factor responsible for this phenomenon may be trafficking of T cells through the basement membrane zone of psoriatic lesions, which presumably causes modification of T cell immunological responsiveness after recirculation.
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