Role In Cross-reactivity Research Articles

A Hypoallergenic Polygalacturonase Isoform from Olive Pollen Is Implicated in Pollen-Pollen Cross-Reactivity

Background: Cross-reactivity reactions between allergenic polygalacturonases (PGs) from different biological sources, especially foods and pollens from the Oleaceae family, have been described using Salsola kali PG (Sal k 6). No PG from olive pollen has been characterized to date, hampering further knowledge about cross-reactions through PGs. Objectives: The aim of this work was to determine the potential allergenicity of the PG from olive pollen and clarify its role in cross-reactivity. Methods: A cDNA-encoding olive pollen PG sequence was subcloned into the pET41b vector and used to transform BL21(DE3) Escherichia coli cells to produce a His-tag fusion recombinant protein. The allergenic properties of olive pollen PG were determined by immunoblotting and ELISA in comparison to Sal k 6. The cross-reactivity potential of the protein with other pollen sources was analyzed by inhibition immunoassays. Results: The existence of other isoforms of Ole e 14 with different allergenicity was confirmed by proteomics and a meta-analysis of the recently reported olive genome. Sal k 6 showed a higher IgE recognition than Ole e 14 regardless of patient sensitization, suggesting the existence of more allergenic Ole e 14 isoforms in olive pollen. IgG and IgE inhibition assays supported the existence of cross-reactions between them and with other PGs from Oleaceae and Poaceae plant families. Conclusions: A new allergen from olive pollen, Ole e 14, has been identified, produced as a recombinant isoform, and structurally and immunologically characterized. Its role in cross-reactivity has been confirmed and, due to its smaller IgE binding capacity, it could have an important role for therapeutic purposes.

Beta-Lactam Hypersensitivity and Cross-Reactivity

Penicillin is the most frequently reported cause of drug allergy, and cross-reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This review evaluates the available data on immunoglobulin E-mediated penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem, and monobactam antibiotics. A MEDLINE search was conducted from 1950 to October 2013, and selected references from review articles were also evaluated. There is a wide variety in reported incidences of cross-reactivity between penicillins and cephalosporins or carbapenems, with early retrospective studies suggesting up to 41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of monobactam antibiotics is frequently employed in the case of a penicillin allergy, as prescribers believe that there is no cross-reactivity between the 2 drug classes. More recent prospective studies suggest that the rates of cross-reactivity with cephalosporins and carbapenems are <5% and <1%, respectively. Similarities in penicillin and cephalosporin side chains may play a role in cross-reactivity between these classes. Cross-reactivity with monobactams is essentially negligible; however, there are some clinical data to support an interaction between ceftazidime and aztreonam, due to the similarity of their side chains. The data reviewed suggest that avoidance of other beta-lactams in patients with type 1 hypersensitivity to penicillins should be reconsidered.

Human TCR Transgenic Bet v 1-Specific Th1 Cells Suppress the Effector Function of Bet v 1-Specific Th2 Cells

Pollinosis to birch pollen is a common type I allergy in the Northern Hemisphere. Moreover, birch pollen-allergic individuals sensitized to the major birch pollen allergen Bet v 1 frequently develop allergic reactions to stone fruits, hazelnuts, and certain vegetables due to immunological cross-reactivity. The major T cell epitope Bet v 1(142-153) plays an important role in cross-reactivity between the respiratory allergen Bet v 1 and its homologous food allergens. In this study, we cloned and functionally analyzed a human αβ TCR specific for the immunodominant epitope Bet v 1(142-153). cDNAs encoding TCR α- and β-chains were amplified from a Bet v 1(142-153)-specific T cell clone, introduced into Jurkat T cells and peripheral blood T lymphocytes of allergic and nonallergic individuals, and evaluated functionally. The resulting TCR transgenic (TCRtg) T cells responded in an allergen-specific and costimulation-dependent manner to APCs either pulsed with Bet v 1(142-153) peptide or coexpressing invariant chain::Bet v 1(142-153) fusion proteins. TCRtg T cells responded to Bet v 1-related food and tree pollen allergens that were processed and presented by monocyte-derived dendritic cells. Bet v 1(142-153)-presenting but not Bet v 1(4-15)-presenting artificial APCs coexpressing membrane-bound IL-12 polarized allergen-specific TCRtg T cells toward a Th1 phenotype, producing high levels of IFN-γ. Coculture of such Th1-polarized T cells with allergen-specific Th2-differentiated T cells significantly suppressed Th2 effector cytokine production. These data suggest that human allergen-specific TCR can transfer the fine specificity of the original T cell clone to heterologous T cells, which in turn can be instructed to modulate the effector function of the disease initiating/perpetuating allergen-specific Th2-differentiated T cells.

Cross‐reactivity of Anisakis simplex: possible role of Ani s 2 and Ani s 3

Anisakis simplex is a fish parasite that can cause allergy in humans. The multiple cross-reactivities of this nematode make diagnostic tests for allergy unreliable, because of frequent false-positive results. To date, only four allergens of A. simplex have been characterized, but their role in cross-reactivity is largely unknown. We performed an amino acid sequence homology analysis, according to the Food and Agriculture Organization/World Health Organization (FAO/WHO) criteria, to identify allergens likely to be cross-reactive with Ani s 2 (paramyosin) and Ani s 3 (tropomyosin) of A. simplex. Next, within segments shared by Ani s 2 or Ani s 3 and homologous proteins, we searched for the occurrence of binding motifs of human leukocyte antigen (HLA) alleles (DRB1*1502, DQB1*0601, or DRB1*0404) known to be genetic risk factors for the development of allergy to A. simplex. We identified a number of proteins belonging to various organisms, which are significantly similar to (and therefore are likely to cross-react with) Ani s 2 and Ani s 3. The presence of binding motifs of HLA DRB1*0404 in Ani s 2, Ani s 3, and homolog proteins also supports our hypothesis. Our results provide a possible molecular explanation of some cross-reactivities reported for A. simplex, and suggest additional ones.

Cross-reactive binding patterns of monoclonal antibodies to DNA are often caused by DNA/anti-DNA immune complexes

Recently, the role of antibodies to DNA in the pathogenesis of systemic lupus erythematosus (SLE) has been reevaluated, since observed cross-reactive binding of anti-DNA to tissue-related antigens might substantially contribute to the inflammatory process of the disease. Evidence of this cross-reactivity has, in part, been obtained from studies with monoclonal anti-DNA. However, we now report that the presence of DNA/anti-DNA immune complexes in monoclonal antibody preparations may be the cause of the observed cross-reactive binding patterns. Studying a panel of anti-DNA producing hybridomas (n = 63), we detected such immune complexes in 76% of the obtained culture supernatants by using an anti-protamine sulphate (PS) ELISA; complexes formed with 1 μg/ml DNA or more were traced in this assay. In cultures of anti-DNA-producing hybridomas, complexes were detected from day 3 on. Treatment of supernatants with DNase reduced the anti-PS reactivity to an average of only 20% of the original reactivity. Contaminating DNA/anti-DNA immune complexes were found to play no role in the cross-reactivity of anti-DNA antibodies with cardiolipin, a minor role in cross-reactivity with dextran sulphate, but a substantial role in the cross-reactivity with heparan sulphate, histones and other nuclear or cytoplasmic antigens. Our results clearly demonstrate that exclusion of the presence of immune complexes in antibody preparations is a prerequisite when cross-reactivity patterns of anti-DNA antibodies are studied.