Elevated Serum IgE Concentrations Research Articles

Cutaneous and systemic IgG4-related disease: a review for dermatologists

Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory condition characterized by IgG4+ plasma cell infiltration of the skin and other organs. Cutaneous forms of the disease may be under recognized owing to poorly defined diagnostic criteria and relatively recent recognition in the literature. The aim of this review is to describe the clinical, histological, and serological presentations of cutaneous IgG4-RD, and to provide an overview of its systemic manifestations for dermatologists. Cases of cutaneous IgG4-RD identified in the literature review were compared to control cases. Clinically, plaque morphology and systemic involvement of the orbit, submandibular gland, lacrimal gland, and parotid gland were associated with a diagnosis of cutaneous IgG4-RD. Histologically, lymphoplasmacytic infiltrate and percentage of IgG4+ plasma cells/IgG+ plasma cells > 40% were associated with the diagnosis. Serologically, neither elevated serum IgG4 nor IgE concentrations were associated with the diagnosis. Dermatologists should consider IgG4-RD as part of the differential diagnosis for nodules, papules, and plaques with an IgG4+ plasma cell infiltrate, especially in middle-aged and elderly males with systemic manifestations of the disease. Diagnosis requires thorough investigation of both cutaneous and systemic clinical and histological presentations.

Hyperimunoglobuline e syndrome: case report

Background Hyperimmunoglobulin E syndrome (HIES) is a rare desease caused by a primary complex immunodeficiency, with IgE serum levels over 2,000U/mL. The syndrome is characterized by the following triad: 1) recurrent staphylococcal abscesses, 2) recurrent airway infections; 3) elevated serum IgE concentration. Our pacient presented signs that are compatible with HIES in distinct moments of his life – microabscesses associated with eczema at adolescence, respiratory infections from childhood until present moment and seric IgE level of over 2,000 in recent dosage.

IgE cross-linking critically impairs human monocyte function by blocking phagocytosis

IgE cross-linking triggers many cellular processes that drive allergic disease. While the role of IgE in mediating allergic responses is best described on basophils and mast cells, expression of the high-affinity IgE receptor on other innate immune cells, including monocytes, suggests that it may affect the function of these cells in allergic environments. To determine the effect of IgE cross-linking on the function of human monocytes. Monocytes purified from healthy donor blood samples were cultured for 4 to 96 hours with media alone, a cross-linking anti-IgE antibody or control IgG. Surface CD14 and CD64 expression and secreted cytokine concentrations were determined. Monocyte function was determined by assessing (1) phagocytosis of Escherichia coli or apoptotic HEp2 cells and (2) killing of intracellular E coli. Select experiments were performed on monocytes obtained from participants with elevated versus normal serum IgE concentrations. IgE cross-linking on monocytes increased CD14 expression and induced secretion of TNF-α, IL-6, and autoregulatory IL-10. These effects were greatest in individuals with elevated serum IgE concentrations. In contrast, IgE cross-linking reduced CD64 expression and significantly impaired phagocytic function without disrupting the capacity of monocytes to kill bacteria. IgE cross-linking drives monocyte proinflammatory processes and autoregulatory IL-10 in a serum IgE-dependent manner. In contrast, monocyte phagocytic function is critically impaired by IgE cross-linking. Our findings suggest that IgE cross-linking on monocytes may contribute to allergic disease by both enhancing detrimental inflammatory responses and concomitantly crippling phagocytosis, a primary mechanism used by these cells to resolve inflammation.

Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation.

Commensal bacteria that colonize mammalian barrier surfaces are reported to influence T helper type 2 (TH2) cytokine–dependent inflammation and susceptibility to allergic disease, although the mechanisms that underlie these observations are poorly understood. In this report, we identify that deliberate alteration of commensal bacterial populations via oral antibiotic treatment resulted in elevated serum immunoglobulin E (IgE) levels, increased steady–state circulating basophil populations, and exaggerated basophil–mediated TH2 cell responses and allergic inflammation. Elevated serum IgE levels correlated with increased circulating basophil populations in mice and subjects with hyperimmunoglobulinemia E syndrome. Furthermore, B cell–intrinsic expression of MyD88 was required to limit serum IgE levels and circulating basophil populations in mice. Commensal–derived signals were found to influence basophil development by limiting proliferation of bone marrow–resident precursor populations. Collectively, these results identify a previously unrecognized pathway through which commensal–derived signals influence basophil hematopoiesis and susceptibility to TH2 cytokine–dependent inflammation and allergic disease.

Extract of Poncirus trifoliata fruit reduces elevated serum IgE concentrations in chemically induced allergic model mice

The fruit of trifoliate orange (Poncirus trifoliate) is widely used for treating allergies including allergenic dermatitis and inflammation in oriental medicine. Increased blood IgE concentration and histamine level following dermatitis, coughing and asthma are the most important clinical symptoms of allergic diseases. Decreases in the elevated serum IgE concentrations are essential in the treatment of allergy because increased IgE blood levels are initiated in allergenic immune disorders. This study was conducted to investigate the activities of an extract of trifoliate orange fruit using 100% methanol followed by extraction with boiling water on the regulation of blood IgE concentration in the U266B1 human myeloma cell line and a 1-chloro-2,4-dinitrobenzene (DNCB) sensitized mouse model. The results revealed that the extracts of trifoliate orange suppressed IgE production in U266B1 cells in a dose dependent manner with or without lipopolysaccharide (LPS) stimulation of the cells. In addition, chemically elevated blood IgE concentrations were dramatically decreased by oral administration, ventral injection, and topical application of the trifoliate orange extracts (TOE). The results indicated that the fraction of TOE should contain an important compound of the fruit of trifoliate orange, and TOE had the ability to reduce IgE concentrations in cultured cells and a chemically sensitized in vivo mouse model.

FcεRIα gene (FCER1A) promoter polymorphisms and total serum IgE levels in Japanese atopic dermatitis patients

Two promoter polymorphisms of the high-affinity IgE receptor alpha-subunit (FcepsilonRIalpha) gene (FCER1A), -66T>C (rs2251746) and -315C>T (rs2427827), were analysed in Japanese atopic dermatitis subjects. Patients with the -315CT/TT genotype tended to have higher total serum IgE levels, while the proportion of -315CT/TT genotype or the -315T allele was significantly higher in those with highly elevated total serum IgE concentrations.

Elevated Serum IgE Concentrations In Systemic Lupus Erythematosus are Related to History of Childhood Allergy, Asthma, and Hives

Elevated Serum IgE Concentrations In Systemic Lupus Erythematosus are Related to History of Childhood Allergy, Asthma, and Hives

Targeted Disruption of MAIL, a Nuclear IκB Protein, Leads to Severe Atopic Dermatitis-like Disease

MAIL (molecule-possessing ankyrin repeats induced by lipopolysaccharide) is a nuclear IkappaB protein that is also termed interleukin-1-inducible nuclear ankyrin repeat protein or inhibitor of nuclear factor kappaB (IkappaB) zeta. In this study, we generated Mail-/- mice to investigate the roles of MAIL in whole organisms. Mail-/- mice grew normally until 4-8 weeks after birth, when they began to develop lesions in the skin of the periocular region, face, and neck. MAIL mRNA and protein were constitutively expressed in the skin of wild type controls, especially in the keratinocytes. Serum IgE was higher in Mail-/- mice than in normal. Histopathological analysis indicated that the Mail-/- skin lesions appeared to be atopic dermatitis (AD) eczema with inflammatory cell infiltration. In addition, markedly elevated expression of some chemokines such as thymus and activation-regulated chemokine was detected in the Mail-/- skin lesions, similar to that observed in the skin of patients with AD. In Mail-/- mice, MAIL-deficient keratinocytes might be activated to produce chemokines and induce intraepidermal filtration of inflammatory cells, resulting in the onset of the AD-like disease. These findings suggest that MAIL is an essential molecule for homeostatic regulation of skin immunity. The Mail-/- mouse is a valuable new animal model for research on AD.

Sensitization to Aspergillus species in the congenital neutrophil disorders chronic granulomatous disease and hyper-IgE syndrome

Background: Hyper-IgE syndrome (HIE) and chronic granulomatous disease (CGD) are congenital immunodeficiency diseases with increased susceptibility to bacterial and fungal infections. Both carry significant morbidity and mortality rates because of invasive infections by Aspergillus species. We encountered 2 patients, one with HIE and one with CGD, in whom detection of sensitization to Aspergillus species preceded the diagnosis of immunodeficiency. With high-dose systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA), an inflammatory disorder caused by sensitization to Aspergillus species, pulmonary abscesses developed in the patient with HIE, and the patient with CGD succumbed to an overwhelming Aspergillus species–induced pneumonia. Objective: We sought to assess the prevalence of sensitization to Aspergillus fumigatus and the presence of diagnostic criteria for ABPA in patients with CGD and HIE. Methods: We measured A fumigatus –specific serum IgE, IgG, and precipitating antibodies as indicators for A fumigatus sensitization in the sera of 18 patients with neutrophil disorders (7 with HIE and 11 with CGD). Hospital records were reviewed for the presence of other diagnostic criteria for ABPA (asthma, elevated total serum IgE concentration, and radiographic abnormalities). Results: Twelve (67%) of 18 patients were sensitized to A fumigatus , as evidenced by precipitating A fumigatus –specific antibodies. Six (33%) of 18 patients had serologic evidence of ABPA. Five of those 6 patients had radiologic abnormalities consistent with a diagnosis of ABPA. One patient with HIE also had asthma, thus fulfilling minimal essential criteria for concurrent ABPA. Conclusions: Patients with HIE syndrome and CGD have a high incidence of sensitization to Aspergillus species. A clinical picture indistinguishable from ABPA may coexist or emerge in patients with CGD or HIE and create a major management dilemma because systemic corticosteroids may accelerate tissue damage and invasive fungal infections. It is important to distinguish individuals with congenital neutrophil disorders from uncomplicated classic ABPA. (J Allergy Clin Immunol 1999;1265-72.)

Effect of topical fluticasone propionate on the mucosal allergic response induced by ragweed allergen and diesel exhaust particle challenge.

Glucocorticoids block the local allergic response in a variety of ways. However, studies have also shown that glucocorticoids increase in vitro IgE synthesis and that treatment with corticosteroids may result in elevated serum IgE concentrations. The ability of topical glucocorticoids to modulate the mucosal IgE response has not been elucidated. We studied the effect of topical steroid (fluticasone propionate) treatment on the local allergic antibody response induced by challenge with either allergen or diesel exhaust particles (DEP). A parallel group study was performed with ragweed-allergic subjects, each subject serving as his/her own control. Nasal provocation challenges were performed on three groups. One group received ragweed allergen, another diesel exhaust particles, and the third saline. The study was repeated following 1 week of treatment with intranasal fluticasone propionate. Each group received the same challenge as before. The concentrations of total immunoglobulins (IgE, IgG, IgA, and IgM), anti-ragweed antibody, IgE- and IgA-secreting cells, epsilon (epsilon) mRNA, and cytokine mRNAs (IL-2, -4, -5, -6, TNF-alpha, INF-gamma) were measured in nasal lavages performed before and at various time points after challenge. Treatment with fluticasone propionate for 7 days caused a decrease in the concentrations of nasal IgE protein, IgE-producing cells, total epsilon mRNA, and all the cytokine mRNAs tested. Furthermore, treatment with fluticasone propionate inhibited the production of allergen-specific IgE and cytokine mRNAs following challenge with ragweed antigen. However, fluticasone treatment did not significantly inhibit the enhancement of mucosal IgE production or cytokine mRNAs observed following nasal challenge with DEP. These results indicate that 1-week treatment with topical fluticasone propionate was effective in blocking local effects of allergen exposure but was unable to inhibit the adjuvant-like effect of DEP.

Molecular concepts of IgE-initiated inflammation in atopic and nonatopic asthma.

Atopic and nonatopic (intrinsic) asthmatics were characterized by a broadly conserved bronchial mucosal proeosinophilic cytokine network in which IL-5 appears to play a key role. Inappropriate IgE-mediated mechanisms may occur in asthma, irrespective of its atopic status, as suggested by elevated serum IgE concentrations and bronchial mucosal expression of FcepsilonRI, IL-4, IL-13, Iepsilon, and Cepsilon. In general, these observations support the concept that these subtypes of asthma, despite showing distinct clinical and biologic features, share many common immunopathologic mechanisms. The most promising future directions of research regarding intrinsic asthma concern the possible identification of novel allergens or antigens, the detailed description of local bronchial mucosal IgE production, and the understanding of a possible macrophage dysfunction. Furthermore, a role for infectious (viral?) or autoimmune processes has yet to be firmly identified in intrinsic asthma. Animal models may also help us to understand the role of IgE and atopy in asthma. Although these are largely IgE-mediated mechanisms, allergen-induced bronchial hyperresponsiveness and eosinophilic inflammation can also occur in the absence of IgE (null mutation of the Cepsilon locus), as shown in a mouse model of hypersensitivity to Aspergillus fumigatus (57). Thus, despite the absence of atopy, IgE-mediated mechanisms may operate in intrinsic asthma (Fig. 1).

Contributions of donor CD4 and CD8 cells to liver injury during murine graft-versus-host disease.

We have determined the capacity of donor CD4 and CD8 T cells to mediate liver injury in the B10.D2 (donor) into BALB/c (host) chronic graft-versus-host disease (GVHD) model. First, we compared the effects of treating GVHD mice with anti-CD4 or anti-CD8 versus no treatment on the liver histology scores and elevated serum IgE levels in this model. We also examined the abilities of purified donor total T, CD4, and CD8 cells to mediate hepatic GVHD lesions. Anti-CD4 and anti-CD8 treatments caused profound depletion of peripheral CD4+ and CD8+ cells, respectively, and produced a relative enrichment of the CD8+ and CD4+ cells in the liver. Hepatic GVHD lesions and elevated serum IgE concentrations were both suppressed by anti-CD4 treatment. Anti-CD8 treatment had no effect on the severity of hepatic lesions and caused a significant increase in serum IgE levels. Attempts to induce hepatic GVHD with purified donor CD4 and CD8 cells were inconclusive because the onset of liver lesions was delayed and the lesions in both groups were contaminated by the opposite subset. Altogether, our results indicate that both hepatic lesions and elevated serum IgE concentrations in this GVHD model are dependent on donor CD4 cells. Donor CD4 cells mediated hepatic GVHD in the absence of CD8 cells. Donor CD8 cells did not produce hepatic GVHD in the absence of CD4 cells and appeared to be dependent on CD4 cells.

Biology and genetics of atopic disease.

Several immunological disorders including allergic rhinitis, bronchial asthma, atopic dermatitis, food allergies, urticaria, nonhereditary angioedema, systemic anaphylaxis, and allergic conjunctivitis are associated with a positive family history, and share a positive response in the Prausnitz-Kuster (wheal and flare) reaction. Studies have shown that 20-30% of the population has a strong genetic predisposition for this condition, termed atopy, whose hallmark is a greatly elevated serum IgE concentration. A great deal is known about the cellular interactions that mediate the sensitization, immediate and late-phase reactions that follow encounters with allergen, as well as about the cell surface and signaling events that result in mediator release from inflammatory cells. Less is known of the genes that confer genetic predisposition for atopy; however, a worldwide effort to identify atopy genes is making significant progress.

Murine acariasis: I. Pathological and clinical evidence suggesting cutaneous allergy and wasting syndrome in BALB/c mouse

We describe here a disease related to mite-associated ulcerative dermatitis in BALB/c mice, a strain previously classified as resistant to this condition. The disease was recognized by pruritic cutaneous pathology and wasting. Pathologic studies showed a marked allergic-type inflammation in the skin. The dominant histologic feature was extensive mast cell infiltration in cutaneous lesions and in lymphoid tissues, associated with a greatly elevated serum IgE concentration. The disease was secondary to infestation with an acarian ectoparasite Myocoptes musculinus, and seemed to represent an allergic reaction to the parasite-derived substances, with an associated wasting syndrome. This condition may be a useful experimental model for allergic diseases.

Antigen presenting cell-independent cytokine and spontaneous in vitro IgE production in patients with atopic dermatitis: Increased interferon-γ production and lack of effects of in vivo low-dose interferon-γ treatment

Atopic dermatitis is characterized by elevated serum IgE concentrations and dysregulation of T-lymphocyte function. To examine the pattern of cytokine production associated with elevated IgE levels, phorbol ester plus ionomycin-stimulated production of interleukin (IL)-4, IL-5, and interferon-γ (IFN-γ) by blood mononuclear cells from 16 patients with atopic dermatitis was compared with that of 18 healthy subjects. Spontaneous in vitro IgE production was also studied longitudinally in patients receiving placebo or daily treatment with 0.05 mg/m 2 IFN-γ. Spontaneous in vitro IgE production and mitogen-driven IL-4 and IFN-γ synthesis did not differ when patients were receiving interferon treatment compared with no treatment. Furthermore, ionomycin plus phorbol ester–stimulated mononuclear cells from patients with atopic dermatitis produced less IL-4 and more IFN-γ than did cells from healthy subjects. IL-5 production by cells from patients with atopic dermatitis did not differ from that of cells from healthy subjects. The ratio of IL-4 to IFN-γ produced in vitro was significantly lower ( p = 0.04) in the cells of patients with atopic dermatitis (0.9) as compared with those of healthy subjects (2.7). The findings suggest that when circulating T cells are stimulated under antigen presenting cell– independent conditions, atopic dermatitis is not characterized by the shift in the reciprocal relationship between IL-4 and IFN-γ production, which has been postulated to explain the pathogenesis of IgE elevation and the therapeutic action of IFN-γ in patients with atopic dermatitis. ( J Allergy Clin Immunol 1995;96:84-91.)

In VitroIgE, Interleukin 4, and Interferon Gamma Production in Children with Differing Serum IgE Concentrations

Interleukin 4 (IL-4) and interferon-gamma (IFN-γ) have been shown to play a role in the regulation of in vitro IgE production by cells from adults. Little information is available regarding the role of these cytokines in influencing IgE production by cells from children. Children ages 3-17 were classified into two groups based upon serum IgE concentrations (>600 U/ml vs. <200 U/ml). Lymphocytes were evaluated for phenotype and IgE production. In vitro IL-4 and IFN-γ production was measured as was the effect of these cytokines on in vitro IgE production by cells obtained from subjects in the two study groups. Children with elevated serum IgE concentrations produced greater amounts of IL-4 than those with lower serum concentrations of IgE. At low dosages of IL-4 (10U) cells from the patients with lower serum IgE concentrations were more sensitive to the effects of IFN-γ, while at higher concentrations of IL-4 (300U) cells from those with higher serum concentrations of IgE were more sensitive to the effects of IFN-γ. The group with higher serum IgE levels had a significantly higher proportion of CD4+ T cells and a greater proportion of cells positive for CD4 and CD29. There are differences in lymphocyte phenotype and IL-4 production in patients with high and normal concentrations of serum IgE. These differences may be important in understanding the basis for different serum IgE concentrations in children.

Elevated Concentrations of Salivary Secretory Immunoglobulin A Anti-Cow’s Milk Protein in Newborns at Risk of Allergy

Secretory immunoglobulin A (SIgA) anti-casein and SIgA anti-beta-lactoglobulin (BLG) were determined in the saliva of 158 healthy mature infants at birth and in breast milk samples using a direct Elisa technique. IgG anti-casein and anti-BLG were measured in serum samples from mothers and newborns (cord blood). A high risk of allergy was defined in 66 infants who had cord blood (CB)-IgE levels greater than or equal to 0.9 IU/ml and/or parents with atopic diseases. Thirty infants had CB levels less than 0.9 IU/ml and parents without clinical symptoms of atopy but with elevated serum IgE concentrations or type I skin reactions to common allergens (low risk). Sixty-two infants had CB-IgE levels less than 0.9 IU/ml and healthy parents (no risk). The groups were matched for social status, smoking and dietary habits. SIgA anti-casein and anti-BLG were detected in all newborns. SIgA anti-casein was significantly higher (p less than 0.05) in high risk infants (medium 157; 50% confidence limits 45-270) than in no risk (48; 25-150) or low risk infants (43; 21-130). SIgA anti-casein values correlated with maternal allergy, maternal allergy plus CB-IgE, but not with paternal allergy. Breast milk SIgA anti-BLG was depressed (p less than 0.05) in mothers with manifest allergy compared to healthy mothers. Determination of salivary SIgA anti-casein may represent an additional screening method for early detection of infants with atopic disposition.

Lower incidence of elevated umbilical cord serum IgE concentration in infants of hepatitis B carrier mothers.

Acta PaediatricaVolume 78, Issue 1 p. 127-128 Lower Incidence of Elevated Umbilical Cord Serum IgE Concentration in Infants of Hepatitis B Carrier Mothers R. Y. M. Tseng, R. Y. M. Tseng Departments of Paediatrics, Chemical Pathology, Obstetrics and Gynaecology Prince of Wales Hospital Chinese University of Hong Kong Shatin, Hong KongSearch for more papers by this authorC. W. K. Lam, C. W. K. Lam Departments of Paediatrics, Chemical Pathology, Obstetrics and Gynaecology Prince of Wales Hospital Chinese University of Hong Kong Shatin, Hong KongSearch for more papers by this authorE. P. L. Loong, E. P. L. Loong Departments of Paediatrics, Chemical Pathology, Obstetrics and Gynaecology Prince of Wales Hospital Chinese University of Hong Kong Shatin, Hong KongSearch for more papers by this authorD. W. Y. Ho, D. W. Y. Ho Departments of Paediatrics, Chemical Pathology, Obstetrics and Gynaecology Prince of Wales Hospital Chinese University of Hong Kong Shatin, Hong KongSearch for more papers by this authorD. P. Davies, D. P. Davies Departments of Paediatrics, Chemical Pathology, Obstetrics and Gynaecology Prince of Wales Hospital Chinese University of Hong Kong Shatin, Hong KongSearch for more papers by this author R. Y. M. Tseng, R. Y. M. Tseng Departments of Paediatrics, Chemical Pathology, Obstetrics and Gynaecology Prince of Wales Hospital Chinese University of Hong Kong Shatin, Hong KongSearch for more papers by this authorC. W. K. Lam, C. W. K. Lam Departments of Paediatrics, Chemical Pathology, Obstetrics and Gynaecology Prince of Wales Hospital Chinese University of Hong Kong Shatin, Hong KongSearch for more papers by this authorE. P. L. Loong, E. P. L. Loong Departments of Paediatrics, Chemical Pathology, Obstetrics and Gynaecology Prince of Wales Hospital Chinese University of Hong Kong Shatin, Hong KongSearch for more papers by this authorD. W. Y. Ho, D. W. Y. Ho Departments of Paediatrics, Chemical Pathology, Obstetrics and Gynaecology Prince of Wales Hospital Chinese University of Hong Kong Shatin, Hong KongSearch for more papers by this authorD. P. Davies, D. P. Davies Departments of Paediatrics, Chemical Pathology, Obstetrics and Gynaecology Prince of Wales Hospital Chinese University of Hong Kong Shatin, Hong KongSearch for more papers by this author First published: January 1989 https://doi.org/10.1111/j.1651-2227.1989.tb10900.xCitations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume78, Issue1January 1989Pages 127-128 RelatedInformation

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.

Abnormal immune responses during hypozincaemia in acrodermatitis enteropathica.

Immune responses were characterized in six patients with acrodermatitis enteropathica during a break in zinc supplementation and during resupplementation. During hypozincaemia the number of T-cells increased but the amount of B-cells and the responses of T- and B-lymphocytes to phytohaemagglutinin, concanavalin A-, pokeweed mitogen- and Staphylococcus aureus stimulations in vitro were subnormal. Cell counts and stimulation results both normalized when serum zinc values improved. One patient was anergic to tuberculin while showing signs of acrodermatitis enteropathica; she converted during supplementation whereas the others were continuously positive. Three females had antibodies against nuclear antigens and slightly elevated serum IgE concentrations; these values were not affected by the break in supplementation. Four females were continuously rheumatoid factor positive. Our findings suggest that zinc deficiency is closely associated with impaired immune responses in patients with acrodermatitis enteropathica, and laboratory markers of autoimmunity occur in a considerable number of the acrodermatitis enteropathica patients, irrespective of their zinc status.