Deborah Ahern

Induction of IgE synthesis in human B cells requires two signals. The first signal is delivered by the cytokine IL-4. The second signal activates B cells and is delivered by T cells, EBV infection, or engagement of the B cell-specific Ag CD40. Hydrocortisone (HC) has recently been shown to synergize with IL-4 to induce IgE synthesis in CD5+ chronic lymphocytic leukemia B cells. We show herein that a combination of HC and rIL-4 induces IgE synthesis in highly purified normal peripheral blood B cells. HC and IL-4 acted directly on B cells, because T cells and monocytes were not required for IgE synthesis. IgE induction was shown to occur in surface IgE- B cells isolated by cell sorting. These results suggest that IgE synthesis results from isotype switching, rather than from expansion of a precommitted B cell population. Furthermore, IgE synthesis was induced in sorted CD5- B cells, indicating that the ability to produce IgE in response to HC and IL-4 is not constrained by CD5 expression. Endogenous IL-6 was critical for induction of IgE synthesis by HC and IL-4, because an anti-IL-6 antibody strongly inhibited IgE production. These data suggest that hormones may play an important role in the regulation of IgE synthesis.

The ligand for CD40 is expressed on activated T lymphocytes and delivers contact-dependent activation signals to B lymphocytes. The mechanisms regulating CD40 ligand gene expression are largely unknown. Optimal expression of CD40 ligand required activation of protein kinase C and a rise in intracellular calcium concentration. CD40 ligand expression was inhibited by pretreatment of T cells with cyclosporin A. Cyclosporin A analogues inhibited CD40 ligand expression with a potency mirroring the ability of each compound to inhibit calcineurin activity, indicating that calcineurin plays a key role in CD40 ligand gene expression. Cyclosporin A inhibited IL-4-driven CD40 ligand-dependent IgE isotype switching in PBMC but did not inhibit IgE synthesis induced by CD40 mAb plus IL-4. PBMC derived from transplant patients receiving cyclosporin A failed to express CD40 ligand upon stimulation. These results suggest that patients receiving cyclosporin A may be deficient in CD40 ligand-dependent T cell help.

Background: Although the American Heart Association promotes telehealth models to improve care access, there is limited literature on its use in underserved populations. This study is the first to compare utilization and quality of life (QoL) for underserved black and Hispanic heart failure (HF) patients assigned to telehealth self-monitoring (TSM) or comprehensive outpatient management (COM) over 90 days. Methods: This randomized controlled trial enrolled 104 patients. Outcomes included emergency department (ED) visits, hospitalizations, QoL, depression, and anxiety. Binary outcomes for utilization were analyzed using chi-square or Fisher's exact test. Poisson or negative binomial regression, repeated-measures analysis of variance, or generalized estimating equations were also used as appropriate. Results: Of 104 patients, 31% were Hispanic, 69% black, 41% women, and 72% reported incomes of <$10,000/year. Groups did not differ regarding binary ED visits (relative risk [RR] = 1.37, confidence interval [CI] = 0.83–2.27), hospitalization (RR = 0.92, CI = 0.57–1.48), or length of stay in days (TSM = 0.54 vs. COM = 0.91). Number of all-cause hospitalizations was significantly lower for COM (TSM = 0.78 vs. COM = 0.55; p = 0.03). COM patients reported greater anxiety reduction from baseline to 90 days (TSM = 50–28%; COM = 57–13%; p = 0.05). Conclusions: These findings suggest that TSM is not effective in reducing utilization or improving QoL for underserved patients with HF. Future studies are needed to determine whether TSM can be effective for populations facing health care access issues.

Immune responses in newborn lymphocytes show a defect in isotype switching from IgM to IgG and IgA. Immunoglobulin isotype switching in B lymphocytes requires a contact-dependent signal from T lymphocytes which is delivered by the ligand for the B cell surface antigen CD40. We investigated the capacity of newborn lymphocytes to express the CD40 ligand and to undergo CD40 ligand-dependent immunoglobulin isotype switching. After stimulation by phorbol ester and ionomycin, newborn lymphocytes expressed markedly decreased amounts of CD40 ligand on their surface compared to normal adult lymphocytes. Northern blot analysis of mRNA derived from activated cord blood lymphocytes also revealed markedly decreased amounts of CD40 ligand mRNA. Decreased expression of CD40 ligand in newborn lymphocytes was associated with a severely decreased ability to undergo T cell-dependent immunoglobulin isotype switching. Newborn lymphocytes synthesized little or no detectable IgE in response to T cell-dependent stimulation by interleukin-4 but synthesized IgE in response to T cell-independent stimulation by CD40 monoclonal antibody and interleukin-4. These results indicate that decreased expression of CD40 ligand in newborn lymphocytes may be the underlying cause of deficient immunoglobulin isotype switching in newborns.