Humoral immunity in steroid-dependent children with asthma and hypogammaglobulinemia.

OBJECTIVE: To determine primary and secondary antibody responses in children with hypogammaglobulinemia attributed to corticosteroid use. RESULTS: In seven patients with steroid-dependent asthma and significant hypogammaglobulinemia (IgG concentration, 275 to 443 mg/dl), antibody responses to protein and polysaccharide antigens were shown to be normal, as were primary and secondary responses to a neoantigen, bacteriophage phi X174. CONCLUSIONS: Patients with asthma, and with hypogammaglobulinemia resulting from steroid therapy, have normal humoral immunity, and immunoglobulin replacement therapy is not indicated.

Role for Ca2+ in expression of cell cycle regulated genes in PAF-stimulated cells.

Platelet-activating factor (PAF) is a powerful stimulator of a wide variety of cells. In transformed human B-lymphoblastoid cell lines, PAF increases intracellular Ca2+ concentrations ([Ca2+]i) and induces the expression of the proto-oncogenes c-fos and early growth response gene-2 (EGR2). Here, we present data that evaluates the role of Ca2+ in the PAF-dependent induction of these cell-cycle activated genes. PAF (10(-7) M) increased c-fos and EGR2 mRNA levels in cells suspended in Ca(2+)-containing medium by 6-10-fold. In PAF-stimulated cells suspended in medium depleted of Ca2+, eliminating Ca2+ influx but not intracellular store release of Ca2+, the induction of gene expression was reduced by approx. 50%. In contrast, buffering of Ca2+ released from intracellular stores but maintaining transmembrane Ca2+ uptake had little effect on gene expression. When both sources of Ca2+ were eliminated, PAF-stimulated expression of these genes was completely prevented. This was not due to any toxicity to the cells since the response to phorbol ester under identical conditions was unaffected. The regulation of c-fos mRNA expression was paralleled by changes in levels of FOS protein. These data indicate that changes in [Ca2+]i, primarily from stimulated entry across the plasma membrane and to a lesser extent release of Ca2+ from sequestered intracellular stores, play an essential role in PAF-dependent triggering of c-fos and EGR2 mRNA expression.

T cells expressing variable elements of T-cell receptor beta 8 and beta 2 chain regulate murine IgE production.

After sensitization to ovalbumin (Ova) by inhalation of nebulized antigen, BALB/c mice respond with an early rise in IgE but not in IgG anti-Ova antibody production. Our purpose here was to analyze the repertoire of T cells that may contribute to regulating this IgE response. Initial study of Ova-reactive T-cell hybridomas showed that they selectively express the T-cell receptor variable beta-chain (V beta) elements 2, 8.1/8.2, and 14. The frequency of T cells bearing these V beta elements in local draining lymph nodes of the airways and lungs (peribronchial-draining lymph nodes) after Ova inhalation was examined. Local sensitization increased the proportion of V beta 8.1/8.2 T cells in the peribronchial-draining lymph nodes, whereas expression of V beta 2 or V beta 14 was similar in sensitized and nonsensitized animals. In the presence of increased antigen concentrations, V beta 8 and V beta 2 T cells were equally reactive to Ova when cell proliferation was assayed. Coculture of Ova-selected V beta 8 T cells from peribronchial-draining lymph nodes and spleens of sensitized animals with primed splenic B cells increased IgE but not IgG production. The V beta 8 increase in IgE production was related to an increase in numbers of IgE-secreting B cells. In contrast, coculture of Ova-selected V beta 2 T cells with sensitized B cells had no stimulatory effect on either IgE or IgG production. Further, addition of V beta 2 cells to V beta 8 cells inhibited the V beta 8-induced augmentation of IgE production. These data indicate that T cells expressing different T cell receptors or, perhaps, different V beta elements may play different roles in IgE production in sensitized mice.

V beta-specific stimulation of human T cells by staphylococcal toxins.

The staphylococcal toxins are responsible for a number of diseases in man and other animals. Many of them have also long been known to be powerful T cell stimulants. They do not, however, stimulate all T cells. On the contrary, each toxin reacts with human T cells bearing particular V beta sequences as part of their receptors for major histocompatibility complex protein-associated antigen. The specificity of these toxins for V beta s puts them in the recently described class of superantigens and may account for the differential sensitivity of different individuals to the toxic effects of these proteins.

Hepatoxicity with encephalopathy associated with aspirin therapy in rheumatoid arthritis.

Encephalopathy secondary to aspirin-induced hepatoxicity developed in three patients with JRA. In each patient clinical and biochemical resolution occurred after discontinuing the drug, but toxicity appeared on rechallenge. Liver biopsies in two patients showed mild nonspecific changes. Acute hepatic decompensation and encephalopathy may occur as a consequence of aspirin hepatoxicity in JRA and justify sequential observations of liver function tests and salicylate levels in such patients.

Antibody deficiency and alopecia.

Three patients are described with antibody deficiency, recurrent infections, and alopecia. One patient had congenital agammaglobulinemia; the other two patients, a brother and sister, had an incomplete antibody deficiency syndrome. The loss of hair in each patient was total; the history was typical of alopecia areata. The association of alopecia and antibody deficiency has not previously been described to our knowledge in children.