Plasma IgE levels, activation marker expression, and cytokine production in non-atopic individuals.

BACKGROUND: Since human IgE serum levels are very low compared with the other immunoglobulin isotypes, most studies have examined the regulation of IgE production in severely atopic individuals where serum IgE levels are increased. Since atopy is a pathologic consequence of increased IgE production, this disease state could have other influences that result in abnormal expression of these parameters and may not reflect normal IgE regulatory mechanisms. OBJECTIVE: To study nonatopic individuals to examine the expression of IgE regulatory cytokines as well as additional cell surface activation markers in relation to serum IgE levels. METHOD: We selected ten individuals at both the lower and higher end of a spectrum of plasma IgE concentrations from 29 nonatopic individuals and compared the differences in cytokine and activation marker expression in relation to IgE production. RESULTS: We found that even upon extensive examination of activation markers on T, B, and NK cell subsets, there are no significant differences in the cell populations or surface marker expression between the high IgE and low IgE groups. Messenger RNA expression in peripheral blood mononuclear cells (PBMCs) of the cytokines IL-4 and IL-6 was significantly higher, whereas IL-10 was lower in the high IgE group. In addition upon in vitro polyclonal stimulation of peripheral blood mononuclear cells, individuals of the high IgE group produced lower levels of IL-2, IFN gamma and IL-10 compared to the low IgE donors. CONCLUSION: Since our results differ from studies using atopic individuals, this study demonstrates the importance of using nonatopic individuals for examining associations between various immune parameters and IgE.

Immunoregulatory abnormalities in patients with Epstein-Barr virus-associated B cell lymphoproliferative disorders.

EBVirus-associated B cell lymphoproliferative disorder (BLPD) is a recognized complication of primary immunodeficiency and organ as well as bone marrow transplantation. Although the nature of the immune defects that predispose to the development of BLPD are unknown, it is postulated that aberrant T cell responses are involved. It is our hypothesis that unbalanced lymphokine production is a major contributory factor to abnormal B cell growth in response to EBV, resulting in BLPD. Since IFN-alpha and IL-4 are important regulators of B cell proliferation and also regulate the synthesis of IgE, we determined serum levels of IFN-alpha, IL-4, and IgE in 8 patients with newly diagnosed BLPD. Comparison was made to healthy recipients of organ transplants on immunosuppressive therapy without BLPD, and normal EBV seropositive controls. Levels of serum IL-4 were significantly elevated in both patients with BLPD as well as in healthy immunosuppressed organ transplant recipients as compared with normal healthy individuals. Patients with BLPD exhibited a combination of significantly lower levels of serum IFN-alpha, and significantly higher levels of serum IgE than either healthy EBV seropositive individuals or healthy recipients of organ transplants on immunosuppressive therapy. These results suggest that imbalance in the proportions of circulating cytokines favoring B cell proliferation may be contributing to the development of EBV-associated BLPD. The potential significance of the finding of low IFN-alpha in patients who develop BLPD is exemplified by our recent success in the treatment of BLPD with IFN-alpha and intravenous IgG.

Thymus-dependent in vivo suppression of IgE synthesis in a murine IgE-secreting hybridoma.

In previous studies we demonstrated that BALB/c mice bearing ascitic tumors of the IgE-secreting hybridoma B53 (epsilon, kappa, anti-dinitrophenyl) developed large numbers of Lyt-1-2+ Fc epsilon R(+) T lymphocytes (T cells with membrane Fc receptors) in response to the elevated serum IgE concentration. The development of Fc epsilon R(+) T lymphocytes was followed by a progressive decrease in the levels of serum IgE in spite of continued proliferation of the hybridoma cells. This sequence of events suggested that the IgE-secreting hybridoma triggered a suppressive immunoregulatory circuit of the host that inhibited IgE expression by the hybridoma cells. The present studies were undertaken to investigate the basis for the subsequent decline in serum IgE levels in mice with B53 tumors and to identify host factors that might be involved in this process. We observed that ascitic B53 cells recovered at increasing time points from BALB/c mice exhibited a selective decline in steady state levels and rates of synthesis of epsilon-heavy chain protein and mRNA. The expression of kappa-light chain protein and mRNA appeared relatively unchanged. The decrease in epsilon-heavy chain gene expression did not occur when B53 tumors were passaged in nu+/nu+ mice or in BALB/c mice depleted of Lyt-2+ cells (suppressor/cytotoxic cell lineage), but did occur in nu+/nu+ mice reconstituted with neonatal BALB/c thymus and in BALB/c mice depleted of L3T4+ cells (helper/inducer cell lineage). That Fc epsilon R(+) T lymphocytes were directly involved in the inhibition of IgE expression was supported by the earlier and more pronounced inhibition of B53 IgE in mice infused with Fc epsilon R(+) T lymphocytes. We conclude from these findings that: 1) the decline in serum IgE levels that occurs toward the end of each generation of in vivo passage of the B53 hybridoma is due to decreased production of IgE by the hybridoma cells, 2) the decreased production of IgE is due to a selective loss of epsilon mRNA expression, 3) the decrease production of IgE by B53 cells is dependent on the presence of Lyt-2+ cells, and 4) Fc epsilon R(+) T lymphocytes participate in the mechanism by which IgE production is suppressed.

Acute leukaemia following malignant ependymoma: a case report.

Though an increasing number of chemotherapy- and radiotherapy-related leukaemias are being reported, acute promyelocytic leukaemia developing as a therapy-related second malignancy is still uncommon. Here we report a case of acute promyelocytic leukemia, microgranular variant, developing in a case of intracranial malignant ependymoma, 1.5 years following treatment with craniospinal radiotherapy.

Pattern of subtypes of acute lymphoblastic leukemia in India.

Leukemic cells from 124 acute lymphoblastic leukemia (ALL) and 31 chronic lymphatic leukemia (CLL) were examined for sheep erythrocyte receptor (E), surface immunoglobulin (SIg) and their reactivity with a panel of monoclonal antibodies recognizing specific surface antigens including pan-T, Common ALL and Ia antigens. In acute lymphatic leukemia, 33% of patients reveal T-cell receptor associated with higher age group, mediastinal mass and high WBC count. Common ALL was predominant between 2 and 9-yr age group. Among chronic lymphatic leukemia, 2 patients were found to be T-CLL while 29 revealed presence of SIg. Ia antigen was detected in 44.4% of ALL and 64% fo CLL patients. The pattern of surface marker observed in our series may be related to our life style, socio-economic and environmental factors.

T-cell acute lymphoblastic leukemia: a report of 60 patients from India.

60 patients studied at the Tata Memorial Hospital from January 1976 to December 1982 were diagnosed as having T-cell acute lymphoblastic leukemia (ALL) by nonimmune rosette formation with sheep red blood cells. The analysis revealed a high incidence of mediastinal mass (50%) and extramedullary infiltration at presentation. The majority of patients (62%) presented with a high WBC count (greater than 50,000/mm3). Unipolar acid phosphatase activity was observed in 90% of patients. The remission rate with a combination treatment of adriamycin, vincristine and prednisolone was found to be 95%. Long-term survival was around 30%. More aggressive or innovative treatments will be needed to improve the results in T-cell ALL.