Prevalence and risk factors for latex glove allergy among female clinical nurses: a multicenter questionnaire study in China.

BACKGROUND: Natural rubber latex glove use is widespread in mainland China, but the prevalence and risk factors for latex glove allergy among clinical nurses have previously been unreported. METHODS: A questionnaire was used to collect information on latex glove-related allergy among clinical nursing staff in 35 hospitals of eight provinces in the southern, central southern, and northern regions of China, and the risk factors were calculated with logistic regression analysis. Some subjects with glove dermatitis were patch tested with a modified European standard series of allergens. RESULTS: Among 8485 female nurses in eight provinces of China, overall prevalence of latex glove allergy was 8.8%. Of 743 symptomatic nurses, 573 (77.1%) and 475 (63.9%) reported symptoms suggestive of glove dermatitis and type I latex allergy, respectively. Of 69 randomly selected subjects with glove dermatitis, 18 (26.1%) had a positive patch to rubber additives. Employment seniority, positive family and personal history of allergic diseases, and longer extent of time spent in a single hospital room were associated with latex allergy, while using >5 pairs of gloves per working day may be a protective factor. CONCLUSION: Chinese nurses are at high risk for latex sensitization. Nurses who develop latex-related symptoms after exposure to latex gloves should undergo screening tests for latex allergy. Low-protein, powder-free natural rubber latex gloves, or latex-free gloves should be widely adopted in China, along with other preventive measures.

Gene expression profiling of patients with latex and/or vegetable food allergy.

BACKGROUND: The prevalence of individuals allergic to latex, exhibiting cross-hypersensitivity with plant-derived food has been frequently reported as the so-called latex-fruit syndrome. Nonetheless, molecular mechanisms underlying allergy to latex and/or fruit are poorly understood. AIM: The aims of this study were to identify candidate genes that may be associated with the pathogenesis of allergy to latex and/or vegetable food, and to assess if similar molecular pathways are involved in both types of hypersensitivity. MATERIALS AND METHODS: DNA microarray analysis was performed to screen the molecular profiles of peripheral blood mononuclear cells isolated from patients with allergy to latex, to fruit, or with latex-fruit syndrome, and from control healthy subjects. RESULTS: Molecular profiling identified an overlapping dataset of genes commonly regulated in all the atopic patients enrolled in this study, suggesting that similar molecular mechanisms are involved in the pathogenesis of allergy to the fruit and/or latex. Several regulators of the innate and acquired immunity reported to polarize the immunological response towards a Th2-mediated immune response were overexpressed in the patients. Evidences suggested that the expression of T-regulatory cells might be defective in allergic patients, as a consequence of a dysregulation of some inflammatory cytokines. Finally, several transcription factors that may be responsible for the Th1/Th2 imbalance were modulated in allergic patients. CONCLUSIONS: This study identified relevant genes that may help to elucidate the molecular mechanisms underlying allergic disease. Knowledges of critical targets, along with transcription factors regulating gene activity may facilitate the development of new therapeutic options.

Impact of interleukin-13 and -18 promoter polymorphisms in health care workers with natural rubber latex allergy.

It is a matter of debate whether single nucleotide polymorphisms (SNP) in the promoter region of interleukin (IL)-13, an IgE regulator, and IL-18, an inducer of immune responses, modulating the respective protein expression, are accompanied by an increased risk of atopy, allergic asthma, and total IgE levels. The suspected associations were noted in health care workers (HCW) with and without latex allergy. IL-13 (-1055C>T) and three IL-18 (-656T>G, -607C>A, -137G>C) SNP were studied in 523 HCW with natural rubber latex (NRL) exposure and diagnosis in the late 1990s. Three hundred and thirty-four HCW displayed NRL sensitization and allergic symptoms, 93 with latex-allergic asthma, and 189 HCW with neither symptoms nor NRL sensitization. SNP analyses were performed by real-time polymerase chain reaction (PCR) using newly developed LightCycler assays. Analysis of IL-13 -1055C>T by analysis of variance (ANOVA) revealed significantly elevated total IgE levels in HCW carrying the CT or TT variant compared with the CC variant. None of the studied SNP showed an association with NRL-specific IgE. The IL-18 variants -656GG and -607CC displayed 99.5% linkage disequilibrium. Frequencies of alleles -656GG and -607CC were elevated in HCW with NRL asthma (48.4%) compared with HCW without symptoms (37.6%). In contrast, IL-18 -137G>C variants displayed an overall homogenous distribution. The association between the IL-13 -1055T allele and elevated total IgE levels confirms the role of a genetic background for total IgE regulation. The studied IL-18 SNP demonstrated no significant association with the clinical outcome, total IgE, or specific IgE in HCW with natural rubber latex allergy.

Latex allergy and filaggrin null mutations.

OBJECTIVES: Natural rubber latex (NRL) contains over 200 proteins of which 13 have been identified as allergens and the cause of type I latex allergy. Health care workers share a high occupational risk for developing latex allergy. Filaggrin null mutations increase the risk of type I sensitizations to aeroallergens and it is possible that filaggrin null mutations also increase the risk of latex allergy. The aim of this paper was to examine the association between filaggrin null mutations and type I latex allergy. METHODS: Twenty latex allergic and 24 non-latex allergic dentists and dental assistants, occupationally exposed to latex, were genotyped for filaggrin null mutations R501X and 2282del4. Latex allergy was determined by a positive reaction or a historical positive reaction to a skin prick test with NRL. RESULTS: 41 individuals were successfully genotyped. Three individuals were filaggrin mutation carriers. One (2.4%) was a 2282del4 heterozygote and two (4.9%) were R501X heterozygote. No homozygote or compound heterozygote carriers were detected. No association between filaggrin null mutations and type I latex allergy was found (p=0.24). Patients with type I latex allergy more often reported contact dermatitis. CONCLUSIONS: This is the first study to examine a highly plausible association between filaggrin null mutations and type I latex allergy. The study subjects were occupationally exposed to latex but no association between latex allergy and filaggrin mutations were detected. Sensitization to latex in the cases in this study may not have occurred through direct skin contact but through the respiratory organs via latex proteins that are absorbed in glove powder and aerosolized.

Genetic predisposition to natural rubber latex allergy differs between health care workers and high-risk patients.

BACKGROUND: In health care workers, the natural rubber latex (NRL) allergy phenotype has been shown to be associated with promoter polymorphisms in interleukins 13 and 18 (IL13 and IL18) when compared with nonatopic controls. However, it is not known whether high-risk patient populations, such as those born with neural tube defects or genitourinary abnormalities, demonstrate a heightened propensity toward the same genetic/immunologic risk factors that have been reported for health care workers. In this study, we tested the hypothesis that single-nucleotide polymorphisms in genes encoding IL13 and IL18 occur at an increased frequency in NRL allergic patients with spina bifida (SB) or bladder exstrophy (BE). METHODS: One hundred twenty subjects (40 SB, 40 BE, and 40 control) were screened using a clinical history questionnaire and NRL-specific immunoglobulin E (IgE) antibody measurements in the blood. Genomic DNA was extracted from peripheral blood lymphocytes and analyzed for single-nucleotide polymorphisms in candidate genes of interest. Univariate and multivariate analyses were performed to identify significant variables with significance defined as P < 0.05. RESULTS: Sensitization (IgE antibody positivity) to NRL allergens was associated with atopic history and number of prior operations and was prevented by the avoidance of NRL beginning at birth. However, unlike health care workers, the NRL allergy phenotype was not significantly associated with promoter polymorphisms in IL13 or IL18 when comparing NRL allergic SB and BE patients with nonsensitized patients and with atopic and nonatopic controls. CONCLUSIONS: In patients born with SB or BE, environmental factors seem to play a greater role in the development of NRL sensitization and overt allergic symptoms than the IL polymorphisms in IL13 and IL18 previously shown to be associated with NRL allergy in health care workers.

In vitro hymenoptera venom allergy diagnosis: improved by screening for cross-reactive carbohydrate determinants and reciprocal inhibition.

BACKGROUND: Immunoglobulin (Ig) E-double positivity for honeybee (HB) and yellow jacket (YJ) venom causes diagnostic difficulties concerning therapeutical strategies. The aim of this study was to clarify the cause and relation of the cross-reactivity in patients with insect venom allergy. METHODS: For this purpose, 147 patients with suspected stinging insect allergy and CAP-FEIA-double positivity were investigated for specific sIgE to additional cross-reactive carbohydrate determinant (CCD)-containing allergens: timothy grass pollen, rape pollen, natural rubber latex (NRL), bromelain, and horseradish peroxidase (HRP). Sera with sIgE to NRL were further investigated with the commercially available recombinant latex allergens. Reciprocal inhibition assays with both venoms and HRP were performed. RESULTS: About 36 of 147 (24.5%) patients had sIgE to both venoms only. However, 111 of 147 (75.5%) additionally reacted to CCD-carrying allergens. 89 of 111 CCD-reactive sera had NRL-sIgE. In cases where inhibition experiments were performed, the NRL-sIgE binding was completely abolished in the presence of HRP. Only nine of 61 sera were positive for at least one recombinant latex allergen; all of them were negative in history and NRL-skin prick test. In 43 sera containing sIgE to CCD, HRP inhibition revealed unequivocal results: In 28 of 43 (65%) an HRP-inhibition >70% of sIgE to one venom occurred, pointing out the relevant venom. In three of 43 sIgE proved to be entirely CCD-specific. CONCLUSIONS: Our data indicate that in cases of IgE positivity to both insect venoms supplementary screening tests with at least one CCD-containing allergen should be performed; HRP being a suitable tool for this test. In addition, subsequent reciprocal inhibition is an essential diagnostic method to specify cross-reacting sIgE results.

Genetic predisposition to latex allergy: role of interleukin 13 and interleukin 18.

BACKGROUND: Occupational exposure of healthcare workers to natural rubber latex has led to sensitization and potentially life-threatening anaphylaxis. Although environmental exposure to natural rubber latex products is necessary for sensitization, it is not sufficient. A number of genetic factors also seem to contribute to the latex sensitization; however, the multigenic nature of the allergic phenotype has made the identification of susceptibility genes difficult. The current study tests the hypothesis that known functional polymorphisms in genes encoding interleukin 4, interleukin 13, and interleukin 18 occur in a higher frequency in healthcare workers with natural rubber latex allergy. METHODS: Four hundred thirty-two healthcare workers with occupational exposure to natural rubber latex were screened using a clinical history questionnaire and latex-specific immunoglobulin E serology. Genomic DNA was extracted from peripheral blood lymphocytes and analyzed for single-nucleotide polymorphisms in candidate genes of interest. Data from cases and controls were analyzed by nominal logistic regression, with P < 0.05 considered significant. RESULTS: The latex allergy phenotype was significantly associated with promoter polymorphisms in IL13 -1055 (P = 0.02), IL18 -607 (P = 0.02), and IL18 -656 (P = 0.02) compared with nonatopic controls. CONCLUSIONS: The significant association of IL13 and IL18 promoter polymorphisms with latex allergy suggests a potential location for genetic control in the induction of latex allergy in individuals and extends the understanding of the genetic basis for the induction of immediate-type hypersensitivity in healthcare workers occupationally exposed to natural rubber latex.

Genetic basis of the latex-fruit syndrome: association with HLA class II alleles in a Spanish population.

BACKGROUND: The latex-fruit syndrome is a well-defined disorder whose genetic background has not been elucidated. OBJECTIVE: To study the genetic basis of the latex-fruit syndrome. METHODS: In a case-control study, we have investigated a carefully selected group of patients allergic to latex, searching for association between latex-fruit allergy and HLA class I and II genes, HLA-DR functional groups, and markers IL4-R1 and FcepsilonRI-betaca . RESULTS: Seventy-eight patients allergic to latex without spina bifida, 33% of them also allergic to fruits, were included in our protocol. Skin prick test results with both a commercial latex extract and purified hevein were significantly greater in patients allergic to latex and fruit than in patients allergic to latex and not fruit. A cutoff point of >7 mm for commercial latex skin prick test diagnosed latex-fruit allergy with a sensitivity of 66.7% (95% CI, 41.0-86.6) and a specificity of 83.3% (95% CI, 68.6-93.0) in our series of patients. No significant differences were found regarding HLA class I, IL4-R1 , or FcepsilonRI-betaca allele distributions. However, comparison of HLA class II allelic frequencies between patients allergic to latex and fruit and patients allergic to latex and not fruit showed significant associations of latex-fruit allergy with DQB1 *0201 (corrected P value, .001; odds ratio, 7.3; 95% CI, 2.6-20.0), as well as with HLA-DR functional group E (corrected P value, .028; odds ratio, 16.0; 95% CI, 1.9-134.1). When comparing allelic distribution among different subgroups of patients allergic to latex, additional significant associations of latex-fruit allergy with DRB1 *0301 and *0901, and of latex and not fruit allergy with DQB1 *0202, DRB1 *0701 and *1101, were demonstrated. CONCLUSIONS: Latex-fruit allergy is associated with HLA-DQB1 *0201, DRB1 *0301, and *0901, as well as with HLA-DR functional group E, whereas latex-not-fruit allergy is associated with DQB1 *0202, and with both DRB1 *0701 and *1101 alleles.

Immunomodulatory effect of endotoxin on the development of latex allergy.

BACKGROUND: Although numerous studies have been conducted delineating the clinical manifestations of latex allergy and characterizing the protein allergens, little is known regarding the natural history of the disease. OBJECTIVE: These studies were undertaken to investigate the immunomodulatory role of inhaled endotoxin on the development of latex-specific IgE-mediated responses to natural rubber latex (NRL) proteins by using a mouse model. METHODS: Female BALB/c mice were exposed to 25 microg of NRL proteins with or without increasing concentrations of endotoxin (50-25,000 EU) through the respiratory tract. Serum antibody levels were evaluated biweekly during the study. After sensitization, mice were challenged with methacholine or NRL proteins, and airway hyperreactivity (AHR) was evaluated with whole-body plethysmography. After NRL challenge, lungs were excised for histopathology, and lung-associated lymph nodes were removed for cytokine mRNA evaluation. RESULTS: When compared with mice exposed to latex alone, mice exposed to latex and endotoxin demonstrated up to 50% lower levels of latex-specific IgE and decreased latex-specific AHR and mucin production. Conversely, these same animals demonstrated increased levels of latex-specific serum IgG2a and IgA antibodies and an increase in IFN-gamma and IL-12 mRNA levels in the draining lymph node cells. Concurrent exposure to LPS with nonammoniated latex resulted in increased alveolitis and nonspecific AHR on respiratory challenge with methacholine. CONCLUSION: Coexposure with LPS and allergen decreased latex-specific IgE but augmented nonspecific AHR. These studies demonstrate that endotoxin associated with NRL gloves can modulate the development of allergic responses to NRL proteins.

Latex allergy in infants younger than 1 year.

BACKGROUND: The prevalence of latex allergy in children is increasing worldwide. Previous multiple operations or atopic predisposition are known risk factors. In contrast, only sporadic cases of latex allergy have been reported in infants younger than 1 year, and the causative latex-containing products or symptoms in young infants have not been studied in detail. OBJECTIVE: The purpose of this study is to analyse the symptoms and risk factors of latex allergy in young infants. METHODS: Cases of latex allergy in infants younger than 1 year were studied in detail. Clinical course, causative latex-containing products were spotted and detailed analysis for latex allergy in patients and patients' parents was performed. CONCLUSION: We report nine cases of latex allergy in infants younger than 1 year. None of them have any abnormality or previous operations. Six patients had atopic eczema/dermatitis syndrome, one patient had bronchial asthma, whereas two patients had no overt allergic diseases. Symptoms of latex allergy were wheezing, swelling of face or lips, facial rash, or anaphylaxis, and causative latex-containing products were teat, pacifier, nose cleaner, teether, balloon, or enema tube. All of the nine patients had positive skin prick test to latex and extract from causative latex-containing products, whereas eight patients had positive serum latex-specific IgE. Study for family history revealed that latex allergy was noted in either father or mother in six patients, in both father and mother in one patient, whereas no latex allergy was noted in parents in two patients. It should be noted that all of these patients had latex-induced symptoms at home. Latex allergy in young infants may not be unusual. Physicians should be aware of latex allergy, and care should be taken to avoid contact with latex in young infants, especially when there is family history for latex allergy.

HLA-DQ8 and the HLA-DQ8-DR4 haplotype are positively associated with the hevein-specific IgE immune response in health care workers with latex allergy.

BACKGROUND: Hevein is one of the most important latex allergens affecting health care workers (HCWs). OBJECTIVE: Because the genetically determined susceptibility is one important factor regulating type I allergy, the association between the hevein-specific IgE immune response and HLA class II alleles of DQB1 and DRB1, DRB3, DRB4, and DRB5 was studied. METHODS: The distribution of HLA-DQB1 and DRB1, DRB3, DRB4, and DRB5 in 269 HCWs with latex allergy, 56 latex-sensitized patients with spina bifida (SB), and 90 nonatopic control subjects under special consideration for hevein-specific IgE was examined. RESULTS: Seventy percent (189/269) of the HCWs with latex allergy and 39% (22/56) of the latex-sensitized patients with SB had increased hevein-specific IgE antibody concentrations (>0.35 kU/L). HLA data analysis revealed significantly increased phenotype frequencies for DQB1*0302 (DQ8; 91/189 [48%]) and DRB1*04 (DR4; 102/189 [54%]) in hevein-positive HCWs with latex allergy compared with the 80 hevein-negative HCWs with latex allergy (DQB1*0302: 16/80 [20%], corrected P value [P (c)] = 7.1 x 10(-4); DRB1*04: 23/80 [29%], P (c) =.01) and with control subjects (DQB1*0302: 16/89 [18%], P (c) = 1 x 10(-4); DRB1*04: 22/90 [24%], P (c) = 3.2 x 10(-4)). The DQ8-DR4 haplotype frequency was significantly elevated in HCWs with hevein-specific IgE antibodies when compared with that in HCWs without hevein-specific IgE antibodies (47% vs 18%, P (c) = 5.3 x 10(-4)) or control subjects (47% vs 18%, P (c) = 9.6 x 10(-4)). In contrast, latex-sensitized patients with SB with hevein-specific IgE antibodies showed an increased but not significant DQB1*0302 frequency (7/22 [32%] vs 2/34 [6%], P =.02, P (c) = not significant) compared with that seen in those without hevein-specific IgE antibodies. CONCLUSION: The DQB1*0302 (DQ8) alone, the DQB1*0302 (DQ8)-DRB1*04 (DR4) haplotype, or both are significantly involved in the hevein-specific IgE immune response in HCWs with latex allergy.