Hevea latex-associated allergies: piecing together the puzzle of the latex IgE reactivity profile.

Introduction: IgE-mediated Hevea latex allergy and associated food-allergies constitute a significant health issue with serious consequences of diagnostic error. Hence, there is a need for more reliable confirmatory diagnostics.Areas covered: Here, we summarize the major limitations of conventional tests using native extracts and describe how piecing together the IgE reactivity profile can benefit correct diagnosis in difficult cases in whom conventional tests yield equivocal or negative results. A diagnostic algorithm integrating traditional sIgE and component-resolved diagnosis (CRD) is presented.Expert opinion: Moreover, it is clear that the discoveries in the field of the Hevea latex proteome will contribute to our understandings and accurate approach of sometimes complex cross-reactivity phenomena that extend beyond the 'latex-fruit syndrome.'

Acute Management, Diagnosis, and Follow-Up of Suspected Perioperative Hypersensitivity Reactions in Flanders 2001-2018.

BACKGROUND: Despite numerous efforts to describe the clinical manifestations and the epidemiology of perioperative hypersensitivity (POH), there remains room to increase awareness among anesthetists and immunologists/allergists. OBJECTIVE: To report the findings of a 17-year survey of suspected POH in Antwerp, Belgium. METHODS: We analyzed clinical and diagnostic data from 715 patients referred because of a suspected POH reaction, between January 1, 2001, and May 31, 2018. A total of 456 patients demonstrating a POH could be queried about subsequent anesthesia. RESULTS: A total of 608 cases formed the final dataset; 208 had a non-life-threatening reaction and 400 a life-threatening reaction. In life-threatening reactions, hypotension was predominating. In the non-life-threatening reactions, 83.9% of the patients displayed cutaneous manifestations. In life-threatening reactions, intravenous adrenaline and fluids were administered in 75.7% and 31%, respectively, and 41.3% had their intervention abandoned. Mast cell activation (MCA) was mainly, but not exclusively, observed in severe grades but did not predict the mechanistic process nor the culprit. A cause was identified in 77.8% of severe and 48.6% of milder cases. Main culprits were neuromuscular blocking agents, latex, cefazolin, and dyes. A total of 156 cases had uneventful anesthesia, except 1 patient who was inadvertently re-exposed to hidden chlorhexidine. CONCLUSIONS: This study highlights that there is room for an improved acute management and an optimized diagnostic workup that should not be restricted to patients with severe reactions and/or showing MCA.

Hevea latex lectin binding protein in C-serum as an anti-latex coagulating factor and its role in a proposed new model for latex coagulation.

A distinct protein specifically recognized by its strong interaction with Hevea latex lectin (HLL) was detected in the aqueous C-serum fraction of centrifuged fresh latex. This C-serum lectin binding protein (CS-HLLBP) exhibited strong inhibition of HLL-induced hemagglutination. The CS-HLLBP was purified to homogeneity by a protocol that included ammonium sulfate fractionation, size exclusion and ion exchange chromatography. The purified CS-HLLBP had a specific HI titer of 0.23microg ml(-1). Its M(r)s analyzed by SDS-PAGE was ca. 40kDa and that by gel filtration was ca. 204kDa. It has a pI value of 4.7, an optimum activity between pH 6 and10 and was heat stable up to 50 degrees C. The HI activity of CS-HLLBP was abolished upon treatment with chitinase. The CS-HLLBP inhibited HLL-induced rubber particle aggregation in a dose dependent manner. A highly positive correlation between CS-HLLBP activity and rubber yield per tapping was found. The correlations for fresh latex (r=0.98, P<0.01) and dry rubber (r=0.95, P<0.01) were both highly significant. This indicated that the CS-HLLBP might be used as a reliable marker for the mass screening of young seedlings to identify and select clones with potential to be superior producers of rubber. A latex anti-coagulating role of the CS-HLLBP is proposed. The findings described in this 3 paper series have been used to propose a new model of rubber latex coagulation that logically describes roles for the newly characterized latex lectin and the two lectin binding proteins.

Cholesterol selectively enhances in vitro latex-specific IgE production in atopic dermatitis patients with latex allergy.

Effect of cholesterol on in vitro latex-specific IgE production by mononuclear cells from atopic dermatitis patients with latex allergy. Cholesterol enhanced latex-specific IgE production in a dose-dependent fashion, and maximal enhancement was achieved at 1 microg/ml. In contrast, cholesterol had no effect on latex -specific IgA or IgG4 production. Study for cytokine production revealed that cholesterol decreased latex-induced production of IFN-gamma and IL-12, while it increased latex-induced production of IL-4, IL-10 and IL-13. These results indicate that cholesterol skews cytokine pattern toward Th2 type. Collectively, cholesterol may increase allergen-specific IgE production, which may in turn aggravate allergic symptoms.

Latex allergen exposure increases exhaled nitric oxide in symptomatic healthcare workers.

The objective of this study was to investigate the clinical and diagnostic impact of baseline exhaled nitric oxide (eNO) levels and latex allergen-induced eNO changes in different healthcare worker groups. Healthcare workers, 31 latex-sensitised and 14 nonsensitised, underwent occupational-type challenge tests with powdered allergenic latex gloves. Sensitised as well as nonsensitised healthcare workers developed a significant eNO increase 1 h after challenge. Conversely, only latex-sensitised employees showed a significant eNO increase 22 h after challenge, which showed a significant relationship with bronchial obstruction (specific airway resistance changes). However, there was no difference in either baseline eNO level or eNO increase after 22 h between asthmatic (n = 13) and rhinitic only (n = 20) responders. The specificity and sensitivity of a 50% eNO increase after 22 h in responders were 100 and 56%, respectively. These results support the assumption that the whole respiratory tract is involved in a combined allergic rhinitis and asthma syndrome. Smoking healthcare workers showed reduced baseline exhaled nitric oxide levels, but, as shown for the first time, an allergen-induced exhaled nitric oxide increase comparable to that of nonsmokers. Corticosteroid therapy inhibited the allergen-induced exhaled nitric oxide change but not the clinical response in the challenge test. These findings suggest that cigarette smoke and corticosteroids initiate distinct molecular mechanisms influencing nitric oxide concentrations in the airways.

Histamine mediates the pro-inflammatory effect of latex of Calotropis procera in rats.

INTRODUCTION: Calotropis procera is known to produce contact dermatitis and the latex of this plant produces intense inflammation when injected locally. However, the precise mode of its pro-inflammatory effect is not known. In present study we have pharmacologically characterized the inflammation induced by latex of C. procera in a rat paw edema model and determined the role of histamine in latex-induced inflammation. METHODS: Inflammation was induced in the hind paw of rats by injecting different doses of dried latex (DL) of C. procera. The inhibitory effect of phenylbutazone, dexamethasone, celecoxib, cyproheptadine, chlorpheniramine and compound 48/80 on edema volume was evaluated and compared with that against carrageenan. The histamine content of DL was measured fluorometrically. RESULTS: DL produced dose-dependent inflammation of the rat paw. Cyproheptadine and chlorpheniramine effectively inhibited DL-induced inflammation (90%; p < 0.01), while anti-inflammatory drugs phenylbutazone, dexamethasone and celecoxib were more effective against carrageenan-induced inflammation. Depletion of mast cell histamine by compound 48/80 produced a significant decrease in DL-induced inflammation as compared with carrageenan (500% versus 25%). DL was also found to contain about 6 microg/g of histamine. CONCLUSIONS: Thus, our study shows that the biogenic amines play a significant role in C. procera latex-induced inflammation and antihistaminic drugs could be effectively used to inhibit inflammatory response elicited by exposure to latex.

Characterization of T cell responses to Hev b 3, an allergen associated with latex allergy in spina bifida patients.

The prevalence of type I allergy to Hevea brasiliensis latex is particularly high among individuals with frequent exposure such as health care workers and patients with spina bifida (SB). Due to a birth defect of the spinal canal and the resulting neurological and orthopedic defects, these patients require multiple surgeries during childhood. SB patients display a unique pattern of sensitization: IgE-reactivity is preferentially directed against Hev b 3 and Hev b 1, two latex allergens with high sequence similarity. In this study, we analyzed the T cell response to Hev b 3 in latex-allergic SB patients using poly-, oligo-, and monoclonal T lymphocyte cultures. All T cell clones (TCC) were CD3/CD4-positive and expressed the alphabeta TCR. According to their cytokine production pattern (IL-4 vs IFN-gamma), 12 of 21 TCC were classified as Th2-like, 2 of 21 were Th1-like, and 7 of 21 belonged to a Th0-like subset. Using 11 T cell lines and 21 TCC, nine T cell stimulating fragments were determined out of 52 overlapping 12-mer peptides representing the complete amino acid sequence of Hev b 3. Ag presentation of one dominant T cell epitope could be associated with a four-amino acid binding motif (YSTS, position 11-13) in the beta 1 chain of HLA-DR molecules expressed by the respective patients. No reactivity was observed when Hev b 3-reactive T cell lines or TCC were incubated with peptides representing homologous parts of the Hev b 1 molecule, i.e., no cross-reactivity between Hev b 3 and Hev b 1 at the T cell level was evident.

Nasal lavage mediator profile and cellular composition of nasal brushing material during latex challenge tests.

BACKGROUND: Recent studies have shown that airborne latex allergens cause allergic rhinitis and bronchial asthma. OBJECTIVE: The aim of this study was to investigate the association between the development of rhinitis reactions during workplace-related inhalative challenge tests and nasal allergic inflammation. METHODS: Thirty-two health care workers (HCWs) with suspected respiratory hypersensitivity to latex allergens underwent an inhalative workplace-related challenge test with powdered latex gloves. Nasal lavage fluid (NALF) and nasal brushing (NAB) material were collected before and after exposure (30 min, 2, 6 and 24 h) to determine mediator and cellular composition. In addition, lung function parameters and nasal flow were recorded. Furthermore, six healthy controls underwent nasal brushing and nasal lavage without latex allergen challenge at the same time intervals. RESULTS: Twenty-six HCWs showed acute rhinitis by contact to airborne latex allergen exposure and 10 of them had an additional asthma response. Only in responders, significantly increased eosinophil levels were found 6 h (P < 0.00001) and 24 h (P < 0.0005) post-challenge when compared with the prechallenge values. The ECP levels measured 2, 6 and 24 h post-challenge in the responder group were significantly elevated when compared with the prechallenge values as well as with the non-responders (6 h: P < 0.05, 24 h: P < 0.00001 afterwards). Only in some concentrated NALF samples of responders collected 30 min post-challenge (seven out of 15) tryptase concentration above the detection limit were found. The NO derivative concentrations in NALF were significantly increased 6 h post-challenge compared with the prechallenge values (P < 0.05) and were significantly higher in responders than in non-responders and in controls (P < 0.002). IL-5 levels increased post-challenge in the responder group with a pronounced effect 6 h after challenge (P < 0.001). Overall, a variety of parameters was significantly correlated (e.g. ECP with NO derivatives, r = 0.792 P < 0.002). CONCLUSIONS: Our data demonstrate for the first time that nasal and bronchial hyperreactivity to airborne latex allergens are associated with an increase of eosinophils and mediators (e.g. ECP, NO derivatives, IL-5, tryptase) in nasal mucosa. The combined use of NAB (for cells) and NALF (for mediators) appears to be a useful model to monitor nasal inflammation during workplace-related challenge tests.