Lupin allergy: a hidden killer in the home.

This review addresses the problem of lupin sensitization in the home environment. We summarize the data currently available on allergy to lupin, which has become, in recent years, a hidden killer in our homes. Since 2006, when lupin was included in European regulations as a food whose presence must be declared, the situation may have changed. Nevertheless, we must take into account the possibility of undeclared allergenic ingredients or the presence of 'hidden' allergens, given that contamination during food production processes may be a great risk for sensitized individuals. Furthermore, the United States, Japan, Australia and New Zealand still do not include lupin among the ingredients that must be listed on foodstuff labelling. Our responsibility is to educate the public so that they are aware of the danger and look for lupin in the labels of products that run the risk of containing it. Lupin allergy can manifest itself in isolation or in parallel to peanut allergy. Identification of the proteins causing possible cross-reactivity is complicated, and new structural studies are needed. To date, it has not been possible to clearly identify the allergens responsible for isolated lupin sensitization in relation to parallel and/or cross-sensitization between lupin and peanut. Most of the allergenic proteins of lupin are α- and ß-conglutins, with a lesser presence of γ- and δ-conglutins. A ß-conglutin corresponding to Lup an 1, with a sequence similar to Ara h 1, has been identified as a major allergen of lupin in patients with allergy following lupin ingestion.

Spontaneous in vitro IgE synthesis: modifications induced by immunotherapy.

In this study, we used an in vitro experimental model with peripheral mononuclear cells (PBMCs) capable of synthesizing IgE to study the possible parallelism between in vitro IgE synthesis and the findings obtained in vivo showing changes in serum IgE values during immunotherapy (IT). Blood samples were extracted from 10 healthy subjects and 39 allergic patients for lymphocyte culture. Allergic patients were classified into five groups according to the time of IT. After incubation for 7 days at 37 degrees C, IgE values were assessed by means of a radioimmunoassay technique modified for low values. Likewise, total serum IgE was assessed. Spontaneous in vitro production of IgE in control individuals (G0) was significantly lower (p < 0.001) than the mean production in allergic patients (GA). When patients were grouped according to the time of IT, we observed that IgE values decreased during the course of IT. The significant differences found between allergic patients and control individuals eventually disappeared from the third year of treatment. We found a statistically significant positive correlation (r = 0.575, p < 0.001) between total serum IgE values and in vitro IgE production in all subjects. We conclude that IT induces a series of variations in lymphocyte IgE production in vitro, which consists of a significant decrease in IgE production from the second year of IT compared with that of patients without IT. IgE production eventually reaches levels similar to those in healthy subjects. The symptomatic recovery shown by all patients was associated with evident immunological changes, which confirms the clinical utility of this treatment in allergic diseases and the importance of its long-term effects.

IgE synthesis suppressor factor: modifications in the course of long-term immunotherapy.

Many authors have described an increase in total serum IgE values during the first few months of immunotherapy (IT), followed by a subsequent decrease. In previous studies in patients undergoing medium-term IT, we detected an IgE synthesis suppressor factor (SF), which was modified during the course of IT. In this study, we investigated the influence of long-term IT on the production of SF and the lymphocyte response to its stimulus. Mixed bidirectional cultures of lymphocytes isolated from healthy individuals (n = 62) and allergic patients (n = 98) were carried out after different periods of IT. The resulting supernatants were subjected to affinity chromatography, from which two fractions were obtained: the first one, likely to contain SF, was added to lymphocyte cultures from 13 allergic patients undergoing no IT (LyG1) and 6 allergic patients with > 3 years of IT (LyG5), in order to assess its inhibitory effect on IgE synthesis. We found that patients undergoing IT for > 3 years presented a significant increase in SF production and an important lymphocyte response to exogenous SF from most of the groups studied, but little response to their own SF. These results could be ascribed to an alteration in the quantity and/or structure of the lymphocyte receptors likely to be sensitive to these factors induced by IT.

Modifications in IgG subclasses in the course of immunotherapy with grass pollen.

In this study, we evaluated the evolution of IgG subclasses in the course of immunotherapy, and related this to the clinical evolution. We selected 226 adult patients with sensitivity to grass pollen alone, undergoing immunotherapy for 0-26 months. The following results may be highlighted: 1) IgG1 increased with immunotherapy and reached its peak at 6 months; 2) IgG2 increased significantly, reaching its peak after 24 months of treatment; 3) IgG3, however, did not present significant modifications in the course of immunotherapy; and 4) IgG4 was high in all patients undergoing immunotherapy compared to patients without hyposensitizing treatment, the peak being reached in the group of patients with the longest course of immunotherapy. Only IgG4 showed a positive and significant (p < 0.05) correlation with the degree of clinical recovery reached with immunotherapy.

IgE synthesis-enhancing factor: modification of its production in the course of long-term immunotherapy.

The isotype-specific mechanisms involved in IgE synthesis are a sophisticated system about which very little is known. Several research groups have demonstrated that there is an enhancing factor (EF) in lymphocyte supernatants which is related to the regulation of the synthesis of IgE, and the influence medium-long-term immunotherapy (IT) exerts on it. Following this line of research, we studied the influence of long-term IT (> 3 years) and the presence of interleukin-4 (IL-4), not only in the different fractions where EF is contained, but also in lymphocyte supernatants after stimulation. Bidirectional mixed lymphocyte cultures were performed between lymphocytes from healthy controls (n = 62) and allergic patients (n = 98) after different periods of IT. The supernatants obtained were submitted to affinity chromatography and the second fractions, containing EF, were added to healthy control lymphocytes (n = 11) in order to test their enhancing effect on IgE synthesis. Modifications in EF production were observed, depending on the duration of IT. There were no detectable levels of IL-4 either in EF fractions or supernatants from stimulated lymphocytes.

Specific IgG subclasses in pollinosis.

We studied IgG subclasses in pollinosis in order to determine the possible immunopathological role of these antibodies, especially antigen-specific IgG4. The selection of pollinosic patients allowed us to observe the influence natural antigenic exposure exerts upon antibodies. On the other hand, we intended to study the possible modifications immunotherapy produces on IgG subclasses. For this purpose, we selected 266 patients who were classified into the following groups: Group I, 65 patients without immunotherapy, 35 of whom were studied during the pollen season and 30 outside the pollen season; Group II, 40 nonpollinosic patients with hypersensitization to Dermatophagoides pteronyssinus were taken as atopic controls; Group III, 161 pollinosic patients with from 3 to 42 months of immunotherapy. For every patient, IgG1, IgG2 and IgG3 against Phleum pratense were determined by means of ELAST (Leti), and IgG4 against the same allergen by means of the ELISA technique developed by us. Our results confirm, first, that untreated pollinosic patients present higher concentrations of IgG4 against Phleum than nonpollinosic patients, and second, that immunotherapy produces significant modifications in the production of antigen-specific IgG.

Extrinsic allergic alveolitis caused by esparto (Stipa tenacissima).

Extrinsic allergic alveolitis (EAA) are clinical entities of growing importance. The discovered etiological agents which can induce them, organic and inorganic substances of low molecular weight which are frequently found in the laboral environment, are every day more numerous. In the group of substances which are rarely implied in EAA etiology, we must mention esparto (Stipa tenacissima), a grass of the graminea family widely used in Spain. The EAA caused by Stipa tenacissima inhalation in known as stipatosis, a disease with poorly systematized clinical manifestations because of the few cases described in the literature so far. Our purpose in this report is to show the second case, in world literature, of EAA correctly characterized.

Changes in the lymphocyte response and in the production of IgE regulatory factors in relation to the course of immunotherapy.

In previous studies we described isotype-specific but antigen non-restricted soluble factors produced by human lymphocytes. In subsequent studies we demonstrated changes in the production of these factors during the course of immunotherapy (IT) by testing them on lymphocytes from normal healthy controls and allergic patients. Through these studies we confirmed that there exists a difference in lymphocytes' responsiveness to soluble factors between both groups. In this report, we investigated the effect of soluble factors on lymphocytes from allergic patients without IT (LyG1) and with IT longer than 2 years (LyG4). Peripheral blood samples were collected from healthy controls and allergic patients at different time periods of IT, and bidirectional mixed cultures were performed with the isolated lymphocytes. Supernatants obtained from chromatography were tested on lymphocytes of allergic patients without IT and with IT greater than 2 years to determine their effect on IgE synthesis. Long periods of IT reduce the production of Suppressor Factors (SF) by allergic patients as well as their responsiveness. Long periods of IT increase the responsiveness of lymphocytes of allergic patients to Enhancing Factors (EF) and decrease EF production. We propose a "receptor hypothesis" to explain these events.

Effect of immunotherapy on the production of IgE regulatory soluble factors. The response of normal lymphocytes.

IgE synthesis is controlled not only by antigen-specific mechanism but also by other factors which selectively affect the IgE isotype. Several groups demonstrated that factors released by lymphocytes were involved in this regulation. Our previous investigations were also directed in this field. Immunotherapy improves clinical symptoms in allergic respiratory diseases and produces cellular and humoral changes that affect IgE production. So we decided to investigate if immunotherapy had any influence in the production of soluble factors. Bidirectional mixed cultures were performed with lymphocytes from healthy controls and allergic patients with different time periods of IT, and the supernatants obtained from chromatography were tested to determine their effect on IgE synthesis of normal lymphocytes. IT time periods exerted influence on the production of enhancing factors. Suppressor factors derived from allergic patients had no effect on IgE synthesis of normal lymphocytes.

Lymphocyte response to IgE regulatory factors in allergic patients during the course of immunotherapy.

In previous studies we demonstrated isotype-specific but antigen non-restricted soluble factors produced by human lymphocytes of allergic patients and normal controls. In a subsequent investigation we isolated these soluble factors from allergic patients classified in various groups according to their immunotherapy (IT) time periods and from controls, and we tested them on lymphocytes of healthy controls. Then, we decided to amplify the study to include the effects on allergic patients' lymphocytes. Bidirectional mixed cultures were grown with lymphocytes from healthy controls and allergic patients with different IT time periods and supernatants obtained from chromatography were tested on lymphocytes of twenty-one allergic patients. None of the enhancing factors showed statistical significant effects on IgE synthesis of allergic lymphocytes. There clearly existed a change in the production of suppressor factors during the course of IT, but the long time period of IT did not increase this production.