Erik Stevens

Haptoglobin directly affects T cells and suppresses T helper cell type 2 cytokine release

T helper cell type 1 (Th1) and type 2 (Th2) immune responses are characterized by a different pattern of cytokine expression following T‐cell activation. Alterations of the ratio of Th1 to Th2 cells are important determinants of susceptibility to viral and parasitic infections, allergies, anti‐tumour responses, and autoimmunity. In this work we bring new evidence for an effect of haptoglobin (Hp), a positive acute‐phase protein, on T‐lymphocyte functions. We show that Hp specifically interacts with both resting and activated CD4+ and CD8+ T cells. This specific binding results in a strong suppression of induced T‐cell proliferation. In addition, Hp exhibits a strong in vitro inhibitory effect on Th2 cytokine release, while the production of interferon‐γ (IFN‐γ) and interleukin‐2 (IL‐2) is only slightly inhibited at high Hp doses. As a result, the presence of Hp promotes Th1 activation over Th2 activation in vivo as evidenced in Hp‐deficient mice. Anti‐CD3 monoclonal antibody injection indeed resulted in predominant IL‐4 production in Hp−/− mice, in contrast to predominant IFN‐γ production in Hp+/+ mice. We conclude that Hp plays a modulating role on the Th1/Th2 balance by promoting a dominant Th1 cellular response. This points to a role of acute‐phase proteins in balancing immune responses.

Prevalence and clinical relevance of specific immunoglobulin E to pollen caused by sting- induced specific immunoglobulin E to cross-reacting carbohydrate determinants in Hymenoptera venoms.

Background Hymenoptera stings can induce specific IgE (sIgE) to carbohydrate determinants (CD) on venom glycoproteins that cross‐react with CD in pollen. sIgE to such cross‐reacting CD (CCD) are believed to have little or no biological activity and thus may cause misdiagnosis of pollen sensitization after a sting.

Purification and characterization of an 18-kd allergen of birch (Betula verrucosa) pollen: Identification as a cyclophilin

BACKGROUND Five birch pollen allergens have been identified so far. In a previous study we detected new birch pollen allergens with an isoelectric point in the range 9.0 to 9.3, present only in extracts prepared at controlled basic pH. OBJECTIVE The purpose of the current study was to purify and characterize those allergens. METHODS The target allergens were purified by ion exchange and hydrophobic interaction chromatography. Analyses were carried out by SDS-PAGE, isoelectric focusing, immunoblotting, and amino acid sequencing. The in vivo reactivity of the allergens was evaluated by skin testing. RESULTS An 18-kd protein, which we named Bet v 7, was purified. This 18-kd protein corresponded to 3 bands on isoelectric-focusing immunoblots that probably represent isoforms. On immunoblots up to 20.8% of birch pollen-allergic patients recognized those allergens. The clinical relevance of Bet v 7 was demonstrated by positive immediate-type skin testing on a patient allergic to birch pollen. Sequencing of an internal peptide yielded an amino acid sequence showing high homology with various plant cyclophilins. The rotamase activity of the protein, inhibited by cyclosporin A, further confirmed that Bet v 7 belongs to the group of cyclophilins. CONCLUSION We have purified a novel allergen of birch pollen, Bet v 7, belonging to the cyclophilin family. Because cyclophilins are highly conserved proteins over the phylogeny, we may postulate that Bet v 7 is a member of a new family of panallergens.

Allergenic and antigenic activity of peptide fragments in a whey hydrolysate formula

Milk hydrolysates, although frequently used as substitutes in cases of cows milk allergy, show a reduced but never a complete abolishment of antigenicity and allergenicity.

Determination of independent risk factors and comparative analysis of diagnostic methods for immediate type latex allergy in spina bifida patients

Background Development of allergy to natural rubber latex in spina bifida patients is determined by several risk factors, such as age, number of interventions and atopic disease that are, however, interdependent. Furthermore, several diagnostic procedures have been analysed, but a comprehensive analysis of their diagnostic significance is lacking.

Depressed T-cell reactivity to recall antigens in rheumatoid arthritis

Reactivity toward soluble recall antigens (Candida albicans, cytomegalovirus, herpes simplex, streptokinase-streptodornase, and influenza) was determined in cultures of peripheral blood mononuclear cells from 41 rheumatoid arthritis patients (with clinically active as well as inactive disease) and from 28 controls. In the group with clinically active rheumatoid arthritis we found an increased incidence of “anergy,” defined as nonreactivity to three or more antigens. In an attempt to explain this decreased antigen reactivity, the latter was correlated with peripheral blood lymphocyte subsets, as defined by two-color immunofluorescence with a panel of eight monoclonal antibodies. We found a significantly lower number of memory T4 cells (CD4+ CD45RA−) and a significantly higher number of the CD3−CD57+ (nonspecific suppressor) cells and of CD3−CD56+/CD16+ (natural killer) cells in anergic RA patients. In the total group of rheumatoid arthritis patients, the antigen reactivity correlated positively with the percentage of memory T4 cells. Antigen reactivity was negatively correlated with the percentage of CD3−CD57+ cells and of the CD3− natural killer cells in peripheral blood. Our data suggest that a decrease in memory T4 cells and an increase in nonspecific suppressor cells may contribute to the impaired cellular immune function in peripheral blood of rheumatoid arthritis patients.

The circulating lymphocyte profiles in patients with discoid lupus erythematosus and systemic lupus erythematosus suggest a pathogenetic relationship

Background  Discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE) are chronic inflammatory diseases of unknown aetiology; the relationship of DLE with SLE has been a subject of debate for many years.

Haptoglobin interacts with the human mast cell line HMC-1 and inhibits its spontaneous proliferation.

Haptoglobin (Hp) is an acute phase reactant produced by hepatocytes. There is evidence for an immunomodulatory potential of Hp, though there is no clear evidence yet about the mechanisms of this action. We have previously shown that Hp interacts with the β2‐integrin CD11b/CD18. In addition, other investigators reported the binding of Hp to B lymphocytes through the CD22 receptor, and to neutrophils through two different receptors.

Occupational allergy to bumble bee venom

The clinical profile of anaphylactic reactions to bumble bees is described and successful immunotherapy with honey bee venom in seven bumble bee allergic patients is reported. The cause of the high frequency of sensitization to pollen in these patients is discussed.Sirs, I read with great interest the article published by A. S. Kochuyt et al. [1], concerning occupational allergy to bumble bee venom. We have recently treated a 37-year-old woman who developed a severe generalized allergic reaction to bumble bee (BB) sting (grade III Mueller classification) while working on a bumble bee farm. Skin tests on two different occasions with honey bee venom, wasp venom and yellow jacket venom, 005 ml each until a maximum concentration of 1 ;Ug/ml was reached were negative. Specific serum IgE antibodies measured with the commercially available ELISA system (Pharmacia, Sweden) gave a class 2 reaction for honey been venom and a class 0 reaction to yellow jacket venom. Confronted with these conflicting results and considering our lack of experience with BB stings, we searched the literature for advice and found an abstract presented at the XVth Congress ofthe European Academy of Allergology and Clinical Immunology, Paris (10-15 May 1992) [2]. In this abstract the authors present six patients with reactions to BB stings ranging from grade I to grade IV according to the Mueller classification. The specific IgE was positive in five ofthe six patients but the material for intracutaneous testing was proven to be unreliable. One of the six patients was chosen for specific immunotherapy. This patient, with a grade IV reaction, was challenged after hyposensitization with honey been venom and this resulted once more in a grade IV reaction. Based on this, we decided not to perform immunotherapy and advised the patient to stop her occupational exposure to BB.

Inhalative occupational and ingestive immediate‐type allergy caused by chicory (Cichorium intybus)

We report a first case of occupational allergy to chicory (Cichorium intybus) in a vegetable wholesaler. Symptoms occurred after oral, cutaneous or inhalatory exposure. The patient also reported reactions after ingestion of botanically related endive (Cichorium endivia) and lettuce (Lactuca sativa.) We identified the responsible allergen by SDS‐PAGE and immunoblot to be a 48‐kDa protein, confined to the non‐illuminated parts of the plants. No cross‐reactivity was found with mugwort (Artemisia vulgaris) ryegrass (Lolium perenne) and birch (Betula verrucosa) pollen, which suggests that the vegetable is the primary allergenic material.