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  1. Yeang HY, Arif SA, Raulf-Heimsoth M, Loke YH, Sander I, Sulong SH, et al.
    J Allergy Clin Immunol, 2004 Sep;114(3):593-8.
    PMID: 15356563 DOI: 10.1016/j.jaci.2004.05.039
    BACKGROUND:
    Sensitization to natural rubber latex has been linked to proteins from medical latex gloves. Various assays to estimate the amount of residual allergenic proteins extractable from latex gloves to assess their potential exposure hazard have inherent weaknesses.

    OBJECTIVE:
    This investigation was aimed at developing 2-site immunoenzymetric assays and identifying appropriate protein markers to assess the allergenic potential of latex gloves.

    METHODS:
    The presence of 6 latex allergens--Hev b 1, 2, 3, 5, 6, and 13--was measured in a cross-section of commercial latex medical gloves by using monoclonal and polyclonal antibody-based 2-site immunoenzymetric assays. The overall allergenic potential of these gloves was assessed by IgE-inhibition assay. Stepwise multiple regression analyses were performed to identify marker allergens that best explained the variation in latex glove allergenicity.

    RESULTS:
    All 6 latex allergens were detected in at least some of the glove samples. Hev b 5 and Hev b 13 were identified as the marker allergens that combined best to explain the variation in the glove allergenicity. The significant multiple correlation (R=0.855) between these 2 markers and glove allergenic potency forms the basis of an assay to gauge latex glove allergenicity.

    CONCLUSION:
    The overall allergenic potential of latex gloves can be estimated by using Hev b 5 and Hev b 13 as indicator allergens. The correlation between glove allergenicity and the level of these allergens was maintained for low-protein gloves (<200 microg/g). This estimation of glove allergenicity was superior to that obtained by using total protein readings.
  2. Goh DL, Chua KY, Chew FT, Liang RC, Seow TK, Ou KL, et al.
    J Allergy Clin Immunol, 2001 Jun;107(6):1082-7.
    PMID: 11398089
    BACKGROUND: We have previously described anaphylaxis induced by edible bird's nest (BN) and demonstrated that this condition is IgE mediated.

    OBJECTIVES: This study aimed at describing the immunochemical properties of the BN allergens. Comparative studies between 3 commercially available sources (according to the country of origin) of BN were also made.

    METHODS: Crude extracts of commercially available processed BN from Sarawak (Malaysia), Thailand, and Indonesia and fresh unprocessed BN from the caves of Sarawak were obtained by means of aqueous extraction. Specific IgE toward these sources were determined by using fluorescence allergosorbent tests (FASTs). Cross-reactivity studies between the 3 sources of commercially available processed BN were carried out by means of FAST inhibition. Immunochemical characterization by means of IgE immunoblot, periodate treatment, and heat stability studies were carried out on fresh unprocessed BN from Sarawak.

    RESULTS: Serum from allergic patients showed differences in IgE binding to the 3 sources of commercially available BN, with the highest levels of specific IgE recorded with the Sarawak source (P

  3. Lai CK, De Guia TS, Kim YY, Kuo SH, Mukhopadhyay A, Soriano JB, et al.
    J Allergy Clin Immunol, 2003 Feb;111(2):263-8.
    PMID: 12589343
    Few data on asthma management are available for the Asia-Pacific region.
  4. Yip E, Cacioli P
    J Allergy Clin Immunol, 2002 Aug;110(2 Suppl):S3-14.
    PMID: 12170237 DOI: 10.1067/mai.2002.124499
    Gloves that will provide a barrier of protection from infectious organisms are an essential feature of medical practice for the protection of both patients and medical personnel. Natural rubber latex has consistently been the most satisfactory raw material for the manufacture of gloves. Certain latex proteins, carried over into the finished product by inadequate manufacturing processes, may pose a risk of provoking allergic reactions in some patients and medical workers. As with any allergy, the risk depends on the route of exposure and dose. Hence, the method of manufacture, including the means used to coat gloves to make donning easy, can influence the eventual exposure of sensitive people to latex allergens. In this article, we describe the several processes in use and their effects on latex protein content.
  5. Yeang HY, Cheong KF, Sunderasan E, Hamzah S, Chew NP, Hamid S, et al.
    J Allergy Clin Immunol, 1996 Sep;98(3):628-39.
    PMID: 8828541 DOI: 10.1016/s0091-6749(96)70097-0
    Two major water-insoluble proteins are located on the surface of rubber particles in Hevea brasiliensis latex. A 14.6 kd protein (Hev b 1), found mainly on large rubber particles (> 350 mm in diameter), and a 24 kd protein (Hev b 3), found mainly on small rubber particles (average diameter, 70 nm), are recognized by IgE from patients with spina bifida and latex allergy. Although Hev b 1 (also called the rubber elongation factor [REF]) has previously been reported as a major latex allergen, this conclusion has been disputed on the basis of results from other studies. The allergenicity of Hev b 1 is verified in this study by testing the recombinant protein generated from its gene. Because allergenicity is confined to patients with spina bifida and not observed in adults sensitive to latex, it is not a major latex allergen. The identification of Hev b 3 as another allergen originating from rubber particles is confirmed by immunogold labeling and electron microscopy. Observations with the monoclonal antibody USM/RC2 developed against Hev b 3 show that the protein has a tendency to fragment into several polypeptides of lower molecular weight (from 24 kd to about 5 kd) when stored at -20 degrees C. There is also indication of protein aggregation from the appearance of proteins with molecular weights greater than 24 kd. Fragmentation of Hev b 3 is induced immediately on he addition of latex B-serum, which is normally compartmentalized in the lutoids in fresh latex. In the preparation of ammoniated latex (used for the manufacture of latex products), the lutoids are ruptured, and the released B-serum reacts with Hev b 3 on the rubber particles to give rise to an array of low molecular weight polypeptides that are allergenic to patients with spina bifida.
  6. Kurup VP, Kelly KJ, Turjanmaa K, Alenius H, Reunala T, Palosuo T, et al.
    J Allergy Clin Immunol, 1993 Jun;91(6):1128-34.
    PMID: 8509575
    BACKGROUND: Patients with latex sensitivity and latex antigens from the United States and Finland, two countries where allergic reactions to latex have been widely reported, were evaluated to determine the spectrum of immune responses.

    METHODS: Sera from 27 patients from Finland and 18 from the United States with latex allergy and control sera from nonsensitive individuals were studied for latex-specific IgE antibodies. Four antigen preparations were used: two extracted from gloves and one each extracted from rubber tree sap from Malaysia and India. All 45 patients had skin prick test results that were positive to latex antigens, and all sera were evaluated by enzyme-linked immunosorbent assay (ELISA) with the various antigens.

    RESULTS: There were considerable differences in the reactivity of patient sera with the different antigens. Only 50% of the sera from patients with latex allergy from Finland demonstrated significant levels of IgE to latex as determined by enzyme-linked immunosorbent assay. These patients showed more reactivity with rubber tree sap antigens than with glove antigens. However, 72% of the patients from the United States demonstrated antibodies to latex, and no marked differences were noted between the antigen extracts.

    CONCLUSIONS: The results indicate that reagents such as rubber tree sap, which contain multiple clinically significant antigenic components, should be included in evaluation of latex allergy and that differences in patient populations may result in serologic variances.

  7. Leung R, Ho P, Lam CW, Lai CK
    J Allergy Clin Immunol, 1997 May;99(5):594-9.
    PMID: 9155823
    BACKGROUND: Allergen sensitization is associated with asthma and allergic disease in children, but such a relationship has not been confirmed in Chinese populations.

    OBJECTIVES: The objective of this study was to evaluate the effects of allergen sensitization and family history of atopy on asthma and allergic disease in Chinese schoolchildren from three southeast Asian populations.

    METHODS: Written questionnaires on respiratory and allergic symptoms were completed by parents of children of secondary-school age (age range 12 to 18 years) in Hong Kong (n = 1062), Kota Kinabalu in eastern Malaysia (n = 409), and San Bu in southern China (n = 737). A subsample of school-children underwent skin prick testing to common inhalant allergens (Hong Kong 471 children, Kota Kinabalu 321, San Bu 647).

    RESULTS: The prevalence of asthma and allergic disease in schoolchildren was highest in Hong Kong, intermediate in Kota Kinabalu, and lowest in San Bu. However, the overall rate of atopic sensitization was similar in the three populations (49% to 63%). House dust mite and cockroach were the two most common allergens causing sensitization and these gave rise to more than 95% of the positive skin test results in all three populations. By regression analysis, mite allergy was associated with rhinitis and asthma in all three populations, and a family history of asthma, rhinitis, or eczema was strongly associated with respective symptoms in the subjects. After adjusting for age, sex, atopic status, and family history of allergic disease, the place of residence remained a significant independent factor for asthma (odds ratio [OR] = 1.0 for Hong Kong, 0.57 for Kota Kinabalu, 0.15 for San Bu, p < 0.001), rhinitis (OR = 1.0 for Hong Kong, 0.59 for Kota Kinabalu, 0.15 for San Bu, p < 0.001), or eczema (OR = 1.0 for Hong Kong, 0.35 for Kota Kinabalu, 1.01 for San Bu, p < 0.001).

    CONCLUSION: Sensitization to indoor allergens was a significant risk factor for asthma and allergic disease, and familial clustering of disease was common in the region. However, the marked difference in disease prevalence in the three southeast Asian populations of Chinese schoolchildren cannot be explained by atopic sensitization and family history alone, and the place of residence was an independent risk factor for asthma and allergies, which suggests an important environmental role in disease pathogenesis.

  8. Twelves S, Mostafa A, Dand N, Burri E, Farkas K, Wilson R, et al.
    J Allergy Clin Immunol, 2019 03;143(3):1021-1026.
    PMID: 30036598 DOI: 10.1016/j.jaci.2018.06.038
    BACKGROUND: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations.

    OBJECTIVE: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort.

    METHODS: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases.

    RESULTS: Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P 

  9. Wagner B, Krebitz M, Buck D, Niggemann B, Yeang HY, Han KH, et al.
    J Allergy Clin Immunol, 1999 Nov;104(5):1084-92.
    PMID: 10550757
    BACKGROUND: Two natural rubber latex proteins, Hev b 1 and Hev b 3, have been described in spina bifida (SB)-associated latex allergy.

    OBJECTIVE: The aim of this study was to clone and express Hev b 3 and to obtain the immunologic active and soluble recombinant allergen for diagnosis of SB-associated latex allergy.

    METHODS: A complementary DNA (cDNA) coding for Hev b 3 was amplified from RNA of fresh latex collected from Malaysian rubber trees (Hevea brasiliensis). PCR primers were designed according to sequences of internal peptide fragments of natural (n) Hev b 3. The 5'-end sequence was obtained by specific amplification of cDNA ends. The recombinant (r) Hev b 3 was produced in Escherichia coli as a 6xHis tagged protein. Immunoblotting and inhibition assays were performed to characterize the recombinant allergen.

    RESULTS: An Hev b 3 cDNA clone of 922 bp encoding a protein of 204 amino acid residues corresponding to a molecular weight of 22.3 kd was obtained. In immunoblots 29/35, latex-allergic patients with SB revealed IgE binding to rHev b 3, as did 4 of 15 of the latex-sensitized group. The presence of all IgE epitopes on rHev b 3 was shown by its ability to abolish all IgE binding to nHev b 3. Hev b 3 is related to Hev b 1 by a sequence identity of 47%. Cross-reactivity between these 2 latex allergens was illustrated by the large extent of inhibition of IgE binding to nHev b 1 by rHev b 3.

    CONCLUSION: rHev b 3 constitutes a suitable in vitro reagent for the diagnosis of latex allergy in patients with SB. The determination of the full sequence of Hev b 3 and the production of the recombinant allergen will allow the epitope mapping and improve diagnostic reagents for latex allergy.

  10. Hamilton RG, Adkinson NF
    J Allergy Clin Immunol, 1998 Sep;102(3):482-90.
    PMID: 9768592
    BACKGROUND: No characterized diagnostic natural rubber latex skin testing material is licensed for use in the United States.

    OBJECTIVE: We have conducted a multicenter clinical skin testing study to document the safety and diagnostic sensitivity and specificity of a candidate Hevea brasiliensis nonammoniated latex (NAL) extract. These data are intended to support the licensing of this reagent for the diagnosis of latex allergy in high-risk populations.

    METHODS: Three hundred twenty-four subjects (304 adults and 20 children) were classified by their clinical history as having latex allergy (LA group, 124 adults and 10 children) or having no latex allergy (NLA group, 180 adults and 10 children). All subjects provided blood samples and then received sequential puncture skin tests (PSTs) at 1, 100, or 1000 microg/mL protein with a bifurcated needle and NAL (Greer Laboratories) from Malaysian Hevea brasiliensis (clone 600) sap. A 2-stage glove provocation test was used to clarify latex allergy status of individuals with positive history/negative PST result and negative history/positive PST result mismatches.

    RESULTS: Twenty-four subjects (15%) originally designated as having LA on the basis of their initial clinical history were reclassified to the NLA group on the basis of a negative glove provocation test result. Of the 134 subjects with LA, 54 (40%) were highly sensitive to latex, with a positive PST result at 1 microg/mL NAL. The Greer NAL reagent produced a positive PST rate (sensitivity) of 95% and 99% in subjects with LA at 100 microg/mL and 1 mg/mL, respectively. The negative PST rate (specificity) in 190 subjects with a negative history with the NAL extract at 100 microg/mL and 1 mg/mL, was 100% and 96%, respectively. Immediately after the PST, mild systemic reactions (mainly pruritus) were recorded in 16.1 % of the adults in the LA group and 4.4% of the adults in the NLA group. No reactions required treatment with epinephrine. Only mild delayed reactions were observed in 9.6% (LA group) and 2.8% (NLA group) of subjects 24 to 48 hours after PST. Mean wheal and erythema diameters measured in the 10 children in the LA group with spina bifida at 100 microg/mL and 1 mg/mL were similar to those observed in the adults in the LA group, suggesting that children are not at increased risk for systemic reactions compared with adults.

    CONCLUSIONS: A suggestive clinical history is necessary but not sufficient for a definitive diagnosis of IgE-dependent latex allergy. These data support the safety and diagnostic efficacy of the Greer NAL, skin test reagent at 100 micro/mL and 1 mg/mL for confirmatory PSTs.

  11. Kuo IC, Cheong N, Trakultivakorn M, Lee BW, Chua KY
    J Allergy Clin Immunol, 2003 Mar;111(3):603-9.
    PMID: 12642844
    BACKGROUND: Dual sensitization by Blomia tropicalis and Dermatophagoides pteronyssinus mites is common in tropical and subtropical countries. The human IgE cross-reactivity between clinical important group 5 allergens, Blo t 5 and Der p 5, remains controversial.

    OBJECTIVE: This study was undertaken to assess the levels of the IgE cross-reactivity between Blo t 5 and Der p 5 by using sera from a large cohort of asthmatic children in subtropical and tropical countries.

    METHODS: Purified recombinant Blo t 5 and Der p 5 were produced in Pichia pastoris and tested against sera from 195 asthmatic children. The IgE cross-reactivity was examined by direct, inhibitory and competitive human IgE enzyme-linked immunosorbent assay as well as skin prick tests.

    RESULTS: The Blo t 5 IgE responses were 91.8% (134 of 146) and 73.5% (36 of 49) for Taiwanese and Malaysian sera, respectively. The Blo t 5 specific IgE titers were significantly higher than those of Der p 5 (P

  12. Czuppon AB, Chen Z, Rennert S, Engelke T, Meyer HE, Heber M, et al.
    J Allergy Clin Immunol, 1993 Nov;92(5):690-7.
    PMID: 8227860
    BACKGROUND: Allergy to latex-containing articles is becoming more and more important because it can result in unexpected life-threatening anaphylactic reactions in sensitized individuals.

    METHODS: A protein of 58 kd with an isoelectric point of 8.45 was purified from raw latex and from latex gloves and identified as the major allergen, completely blocking specific IgE antibodies in the serum of latex-sensitized subjects. The allergen is a noncovalent homotetramer molecule, in which the 14.6 kd monomer was identified, by amino acid composition and sequence homologies of tryptic peptides, to be the rubber elongation factor found in natural latex of the Malaysian rubber tree.

    RESULTS: Competitive immunoinhibition tests showed that the starch powder covering the finished gloves is the airborne carrier of the allergen, resulting in bronchial asthma on inhalation. The purified allergen can induce allergic reactions in the nanogram range.

    CONCLUSION: The identification of the allergen (Hev b I) may help to eliminate it during the production of latex-based articles in the future.

  13. Kurup VP, Kumar A, Kelly KJ, Fink JN
    J Allergy Clin Immunol, 1993 Nov;92(5):638-43.
    PMID: 8227854 DOI: 10.1016/0091-6749(93)90005-z
    Several hybridomas were produced against antigens extracted from the latex sap of Hevea brasiliensis. One of the monoclonal antibodies (LA-E3) reacted with antigens demonstrating binding to patient sera on crossed enzyme immunoelectrophoresis. This monoclonal antibody reacted with 2 of 10 glove extracts studied and with both Malaysian and Indian latex plant extracts. The antigens purified with monoclonal antibody affinity chromatography demonstrated specific IgE in the sera of patients with latex allergy as determined by ELISA. This monoclonal antibody can thus be utilized to obtain reliable antigens useful in the diagnosis of latex sensitivity, although additional antigens will likely be necessary to enhance sensitivity and specificity.
  14. Hamilton RG, Adkinson NF
    J Allergy Clin Immunol, 1996 Nov;98(5 Pt 1):872-83.
    PMID: 8939150
    BACKGROUND: Nonammoniated latex, ammoniated latex, and rubber glove extracts are the only sources of natural rubber (Hevea brasiliensis) latex that have potential for use as skin testing reagents in the diagnosis of latex allergy. Their diagnostic sensitivity and specificity as skin test reagents are unknown.

    OBJECTIVE: We conducted a phase 1/2 clinical study to examine the safety and diagnostic accuracy (sensitivity and specificity) of nonammoniated latex, ammoniated latex, and rubber glove extracts as skin test extracts to identify the most efficacious source material for future skin test reagent development.

    METHODS: Twenty-four adults not allergic to latex, 19 adults with hand dermatitis or pruritus, and 59 adults with a latex allergy were identified by clinical history. All provided blood and then received puncture skin tests and intradermal skin tests with nonammoniated latex, ammoniated latex, and rubber glove extracts from Malaysian H. brasiliensis latex by use of sequential titration. A glove provocation test and IgE anti-latex RAST were used to clarify positive history-negative skin test response and negative history-positive skin test response mismatches.

    RESULTS: All three extracts were biologically safe and sterile. After normalization to 1 mg/ml of total protein, all three extracts produced equivalent diagnostic sensitivity and specificity in puncture skin tests and intradermal skin tests at various extract concentrations. Optimal diagnostic accuracy was safely achieved at 100 micrograms/ml for intradermal skin tests (e.g., nonammoniated latex: puncture skin test sensitivity 96%, specificity 100%; intradermal skin test sensitivity 93%, specificity 96%). The presence of IgE antibody in skin was highly correlated with IgE anti-latex in serum (nonammoniated latex: r = 0.98, p < 0.001; ammoniated latex: r = 0.94, p < 0.001; rubber glove extract: r = 0.96, p < 0.001). All five available subjects with a positive history, negative skin test response, and absence of IgE antibody in serum had a negative glove provocation test response, indicating no clinical evidence of latex allergy. No systemic or large local allergic reactions were observed with puncture skin tests or intradermal skin tests.

    CONCLUSIONS: Equivalent diagnostic sensitivity and specificity were observed with the nonammoniated latex, ammoniated latex, and rubber glove extract skin test reagents after normalization for total protein; nonammoniated latex may be considered the reagent of choice on the basis of practical quality control and reproducibility considerations.

  15. Ismail IH, Lay C, H A Majid N, Lee WS, Lee BW, Abdul Latiff AH, et al.
    J Allergy Clin Immunol, 2020 11;146(5):1005-1007.
    PMID: 32860819 DOI: 10.1016/j.jaci.2020.05.057
  16. Hussain S, Berki DM, Choon SE, Burden AD, Allen MH, Arostegui JI, et al.
    J Allergy Clin Immunol, 2015 Apr;135(4):1067-1070.e9.
    PMID: 25458002 DOI: 10.1016/j.jaci.2014.09.043
  17. Wang CW, Tassaneeyakul W, Chen CB, Chen WT, Teng YC, Huang CY, et al.
    J Allergy Clin Immunol, 2021 04;147(4):1402-1412.
    PMID: 32791162 DOI: 10.1016/j.jaci.2020.08.003
    BACKGROUND: Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole-induced SCAR remains unclear.

    OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR.

    METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia.

    RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1).

    CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.

  18. Neva FA, Kaplan AP, Pacheco G, Gray L, Danaraj TJ
    J Allergy Clin Immunol, 1975 Jun;55(5):422-9.
    PMID: 1138016
    The diverse clinical syndromes characterized by asthmatic symptoms, transient pulmonary infiltrates, and eosinophilia have tended to obscure the specific association of one such entity with filarial infections. Serum IgE levels were determined before and after therapy in a group of well-characterized patients with tropical eosinophilia (TE), studied earlier in Singapore. The mean serum IgE level in 14 cases before treatment with diethylcarbamazine was 2,355 ng. per milliliter, with a trend but statistically nonsignificant decrease in levels to 600-1,000 ng. occurring 8 to 12 weeks after therapy. Leukocyte and eosinophil counts showed a rapid reduction after treatment, and although mean complement-fixing (cf) titers to Dirofilarial antigen tended to decrease, they were not significantly reduced until 5 to 6 weeks. The historical development of evidence supporting the filarial etiology of TE was reviewed. Many basic questions engendered by the clinical syndrome of tropical eosinophilia make it an excellent model for study of the immunopathology of parasitic infections.
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