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WO1995007298A1 - Antigenes du latex de caoutchouc naturel pouvant causer des reactions allergiques - Google Patents

Antigenes du latex de caoutchouc naturel pouvant causer des reactions allergiques Download PDF

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Publication number
WO1995007298A1
WO1995007298A1 PCT/US1994/010226 US9410226W WO9507298A1 WO 1995007298 A1 WO1995007298 A1 WO 1995007298A1 US 9410226 W US9410226 W US 9410226W WO 9507298 A1 WO9507298 A1 WO 9507298A1
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Prior art keywords
antigen
antibody
latex
sample
nrl
Prior art date
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Ceased
Application number
PCT/US1994/010226
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English (en)
Inventor
Harri Alenius
Kevin J. Kelly
Viswanath P. Kurup
Kristiina Turjanmaa
Jordan N. Fink
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Ansell Inc
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Ansell Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ansell Inc filed Critical Ansell Inc
Priority to AU78326/94A priority Critical patent/AU7832694A/en
Publication of WO1995007298A1 publication Critical patent/WO1995007298A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/16—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from plants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/415—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants

Definitions

  • the invention relates to the field of natural rubber latex (NRL) antigens, which can cause serious allergic reactions in humans or mammals sensitized to such antigens.
  • NRL natural rubber latex
  • the present invention additionally relates to antibodies, both polyclonal and monoclonal, which are capable of recognizing and binding to the NRL antigens of the invention.
  • the present invention further relates to methods of use of the NRL antigens and antibodies of the invention.
  • NRL natural rubber latex
  • NRL proteins that cause such allergic reactions are found in raw NRL (sap of the rubber tree, Hevea brasxliensis) and may be eluted from a wide variety of manufactured products, such as surgical gloves, catheters and other medical devices, as well as from non-medical rubber products like household gloves, condoms and toy balloons.
  • the amount of extractable rubber proteins is not necessarily proportional to their antigenicity [3].
  • allergenic proteins with molecular weights ranging mostly between 10 to 100 kilodaltons (kD), have recently been detected in NRL, ammoniated NRL and extracts of latex gloves [4-7], but their overall biological significance has not yet been established.
  • the present invention relates to an allergenic protein of about 27 kilodalton (kD) present in natural rubber latex products.
  • Methods of obtaining and using the purified protein of about 27 kD are also disclosed in the present invention.
  • the 27 kD protein of the invention can be used to detect the presence of antibodies specific for the 27 kD protein in a patient. Patients having antibodies to the 27 kD protein of the invention are at risk in developing an allergic reaction upon future exposure to latex products.
  • the invention additionally pertains to antibodies (polyclonal or monoclonal) or fragments of such antibodies, which specifically bind to the 27 kD protein of the invention.
  • Use of such antibodies allows for the detection of the 27 kD NRL antigen.
  • Use of these antibodies is particularly suited for detecting the presence or absence of the NRL antigen of the invention in a finished latex product such as surgical or exam gloves. Testing latex products in the manufacturing process provides a screen for safe products for use on individuals allergic to particular NRL antigens.
  • Figure 1 shows an immunoblot analysis of IgE binding to NRL antigens in sera from 20 latex allergic patients.
  • the notations in Fig. 1 have the following meanings.
  • C control subject.
  • Patient numbers equal to those given in Table 1.
  • Molecular weight markers (kD) are indicated on the left side of each of the two geographic patient groups. Description of the Preferred Embodiments
  • the NRL antigen of about 27 kD can be isolated from the sap of Hevea brasllie ⁇ sl ⁇ .
  • the antigen of the invention can be prepared by extracting the antigen from latex products such as latex gloves, catheters and other medical devices or instruments. Non-medical rubber products can be used to extract the antigen of the invention.
  • Other potential sources of the NRL antigen of the invention will be readily apparent to those of ordinary skill in the art.
  • the 27 kD antigen is a protein
  • standard extraction and purification techniques can be used to isolate and purify the antigen of the invention.
  • Such techniques commonly employed include extraction, precipitation, ion exchange chromatography, affinity chromatography, gel filtration and the like.
  • the preferred method to isolate the NRL antigen of the invention is by affinity chromatography using a monoclonal antibody bound to a column matrix.
  • the NRL antigen of about 27 kD can be substantially purified from the sources described above.
  • the term “substantially pure” or “substantially purified” is meant to describe a protein which is substantially free of any compound normally associated with the protein in its natural state, i.e., substantially free of contaminating proteins and other components. The term is not meant to exclude the presence of minor impurities that do not interfere with the antigenic or binding activity of the protein.
  • the present invention concerns antibodies that are capable of binding or directed against the 27 kD protein of the invention.
  • An antibody is said to be "capable of binding” or “directed against” a protein if it is capable of specifically reacting with the protein, thereby forming an antigen-antibody complex.
  • antibody or “monoclonal antibody” (Mab) as used herein is meant to include intact molecules as well as fragments of such molecules capable of binding the antigen of the invention.
  • antibody fragments include Fab and F(ab') 2 fragments.
  • Other antibody fragments that may be used in the invention will be readily apparent to those of skill in the art.
  • the antibodies used in the present invention may be prepared by any of a variety of methods.
  • a protein preparation containing the 27 kD antigen can be administered to an animal to induce the production of sera containing polyclonal antibodies capable of binding the antigen.
  • a preparation of the antigen of the invention is purified to render it substantially free of natural contaminants. The purified preparation is then introduced into an animal in order to produce polyclonal antisera of greater specific activity.
  • the antibodies of the present invention also include monoclonal antibodies (or fragments thereof).
  • Monoclonal antibodies can be prepared using well-known hybridoma technology. In general, such procedures involve immunizing an animal with substantially pure NRL antigen.
  • the splenocytes of the immunized animal are extracted and fused with a suitable myeloma cell line. Any suitable myeloma cell line can be employed in accordance with the present invention.
  • the resulting hybridoma cells are selectively maintained in HAT medium, and then cloned by limiting dilutions.
  • the hybridoma cells obtained through such a selection are then assayed to identify clones that secrete antibodies capable of binding to the antigen of the invention.
  • Fab and F(ab') 2 and other fragments of antibodies can be used in the methods disclosed herein.
  • Such fragments are typically produced by proteolytic cleavage using enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab') 2 fragments).
  • enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab') 2 fragments).
  • hapten-binding fragments can be produced through recombinant DNA technology or through synthetic chemistry.
  • the antibody or fragments of antibodies of the invention can be used to detect the presence or absence of the 27 kD NRL antigen in a sample. Detection can be accomplished using any of a variety of assays well known in the art. Briefly, the 27 kD NRL antigen of the invention can be detected by contacting a sample with an antibody specific for the 27 kD NRL antigen. The sample and antibody mixture are incubated for a time and under conditions sufficient for the antibody and antigen in the sample to form an antigen-antibody complex. The antigen-antibody complex may then be detected using well known detection techniques.
  • Examples of materials that may contain the 27 kD NRL antigen of the invention include, but are not limited to, medical latex products such as gloves, catheters, and surgical devices or instruments. Non-medical latex products may also be tested with the antibodies of the invention for the presence of the 27 kD NRL antigen.
  • Antibodies or fragments thereof can be labeled using any of a variety of labels and methods of labeling.
  • types of labels that can be used in the present invention include, but are not limited to, enzyme labels, radioisotopic labels, fluorescent labels, toxin labels, and chemiluminescent labels.
  • suitable enzymic, radioactive, flourescent, toxin and chemiluminescent lables will be readily apparent to one of skill in the art. Those of ordinary skill in the art will know of other suitable labels that can be employed in accordance with the invention.
  • Binding of labels to antibodies or fragments thereof can be accomplished using standard techniques commonly known to those of ordinary skill in the art.
  • Examples of coupling techniques include the glutaraldehyde method, the periodate method, the dimaleimide method, the m-maleimido-benzyl-N- hydroxy-succinimide ester method, and the like.
  • the detection of the NRL antigens of the invention can be improved through the use of carriers.
  • an antibody specific for the 27 kD antigen can be bound to a carrier to aid in the detection of the antigen.
  • Well-known carriers include glass, polystyrene, polypropylene, -1- polyethylene, dextran, nylon, amylases, natural and modified celluloses, polyacrylamides, agaroses, and magnetite.
  • the nature of the carrier can be either soluble to some extent or insoluble for the purposes of the present invention.
  • the support material can have virtually any possible structural configuration so long as the coupled molecule is capable of binding to an antigen.
  • the support configuration can be spherical, as in a bead, or cylindrical, as in the inside surface of a test tube, or the external surface of a rod.
  • the surface can be flat such as a sheet, test strip, etc.
  • the antibodies of the present invention can also be adapted for utilization in an immunometric assay, also known as a "two-site” or “sandwich” assay.
  • an immunometric assay also known as a "two-site” or “sandwich” assay.
  • a quantity of unlabeled antibody, or fragment of antibody is bound to a solid support that is insoluble in the fluid being tested (i.e. , blood, lymph, liquified stools, tissue homogenate, etc.), and a quantity of detectably labeled soluble antibody is added to permit detection and/or quantitation of the ternary complex formed between solid-phase antibody, antigen, and labeled antibody.
  • Typical immunometric assays include "forward" assays in which the antibody bound to the solid phase is first contacted with the sample being tested to extract the antigen from the sample by formation of a binary solid phase antibody-antigen complex. After a suitable incubation period, the solid support is washed to remove the residue of the fluid sample, including unreacted antigen, if any, and then contacted with the solution containing a quantity of labeled antibody (which functions as a "reporter molecule"). After a second incubation period to permit the labeled molecule to complex with the antigen bound to the solid support through the unlabeled antibody, the solid support is washed a second time to remove the unreacted labeled antibody.
  • This type of forward sandwich assay may be a simple "yes/no" assay to determine whether the antigen is present or may be quantitative by comparing the measure of labeled antibody with that obtained for a standard sample containing known quantities of antigen.
  • a simultaneous assay involves a single incubation step as the antibody bound to the solid support and labeled antibody are both added to the sample being tested at the same time. After the incubation is completed, the solid support is washed to remove the residue of fluid sample and uncomplexed labeled antibody. The presence of labeled antibody associated with the solid support is then determined as it would be in a conventional "forward" sandwich assay.
  • stepwise addition of a solution of labeled antibody to the fluid sample is followed by the addition of unlabeled antibody bound to a solid support after a suitable incubation period is utilized. After a second incubation, the solid phase is washed in conventional fashion to free it of the residue of the sample being tested and the solution of unreacted labeled antibody. The determination of labeled antibody associated with a solid support is then determined as in the "simultaneous" and "forward" assays.
  • kits may comprise a carrier means being compartmentalized to receive in close confinement one or more container means such as vials, test tubes, and the like.
  • Each of said container means comprises one of the separate elements to be used in the method.
  • one of said container means can comprise an antibody specific for the 27 kD antigen.
  • Such antibody can be bound directly to the inner walls of a container.
  • a second container can comprise detectably labeled antibody in lyophilized form or in solution.
  • the carrier can contain, in addition, a plurality of containers each of which comprises different, predetermined and known amounts of antigen. These latter containers can then be used to prepare a standard curve from which can be interpolated the results obtained from the sample containing the unknown amount of antigen.
  • the 27 kD NRL antigen of the invention include the detection of antibodies specific for the 27 kD antigen in a sample obtained from a patient. Assays to detect the antibody specific for the NRL antigen can be accomplished by any of a variety of assay methods. Briefly, the method to detect an antibody in a sample comprises contacting a sample with the 27 kD NRL antigen of the invention. The sample-antigen mixture is incubated for a time and under conditions sufficient for the antigen and the antibody in the sample to form an antigen-antibody complex. The formation of the antigen-antibody complex can then be determined using conventional techniques.
  • assay techniques are disclosed in Section C in the Description of the Preferred Embodiment. However, the assays described in Section C are modified to the extent needed to use an antigen rather than an antibody as the detecting component of the assay.
  • a quantity of unlabeled 27 kD antigen is bound to a solid support.
  • the solid phase is contacted with a sample suspected of containing antibodies to the 27 kD NRL antigen to form a binary solid phase antigen-antibody complex.
  • a detectably labeled antibody can then be added to permit detection of the ternary complex formed between the solid phase antigen, antibody, and labeled antibody.
  • the antigen can be labeled using any of a variety of labels and methods of labeling.
  • labels include enzyme labels, radioactive labels, fluorescent labels, toxin labels and chemiluminescent labels. Coupling these labels to an antigen can be accomplished using standard techniques known to those of ordinary skill in the art.
  • various samples can be assayed.
  • biological samples obtained from a patient can be body tissue, body fluids (such as blood, urine, tear drops, saliva, serum, and cerebrospinal fluid) , feces, cellular extracts, and the like.
  • body fluids such as blood, urine, tear drops, saliva, serum, and cerebrospinal fluid
  • feces cellular extracts
  • biological samples obtained from patients suffering from spina bifida or other congenital defects can be used in accordance with the present invention.
  • the latex from Hevea brasillensis was collected in Malaysia directly into containers, deep-frozen immediately, and stored at -70°C.
  • NRL was centrifuged at 100,000 g for 90 minutes, following which the supernatant was collected and stored at -70°C.
  • antigen was prepared by diluting the sap of the latex tree in saline or by extracting latex gloves in buffered saline for 24 hours.
  • Sera were obtained from 11 latex allergic children (5 females and 6 males) aged 1 to 15 years, 3 of whom had spina bifida, 4 had other congenital anomalies and histories of multiple operations and 4 had no associated anomalies or histories of surgical operations. Sera were also obtained from 9 adult latex allergic patients (7 females and 2 males, 6 of whom were health care workers) aged 32 to 66 years, all presenting with cutaneous symptoms. Serum samples from 10 non-allergic adult subjects served as controls. All 20 patients were positive in skin prick testing with two surgical latex glove extracts (Exona , Semperit, Vienna, Austria and Triflex , Baxter, Lessines, Belgium) prepared as previously described [13] and all controls were negative. Rubber Extract
  • SAP Hevea brasiliensis
  • the total protein concentration of the SAP was determined using the Bradford's or Lowry's method with bovine gamma globulin as the standard. Total protein staining of the extract was performed with a commercial kit (Amersham, UK) as previously described [6]. Immunoblotting
  • NRL total protein concentration adjusted to 450 ⁇ g/ml
  • electrophoresis buffer containing 2% sodium dodecyl sulphate (SDS) and 5% 2 ⁇ -mercaptoethanol and kept in boiling water for 2 minutes.
  • SDS sodium dodecyl sulphate
  • Electrophoresis was carried out for 45 minutes at a constant voltage of 200 V (Mini Protean II Cell; Bio-Rad, Richmond, Calif., USA).
  • the proteins were transferred from the gel to 0.45- ⁇ m pore size nitrocellulose filters (Trans-Blot; Bio-Rad) in an electroblotting buffer containing 25 mmol of Tris-HCl, 150 mmol of glycine and 20% methanol, pH 8.3, for 1 hour at 100 V (Mini Trans-blot cell, Bio-Rad).
  • the membrane was stained with Ponceau-S red to demonstrate successful transfer of proteins. The membrane was then cut into 3-mm wide strips, washed 3 times for 5 minutes in 0.1% Tween-tris-buffered saline (TBS) and incubated for 1 hour in a blocking buffer containing 5% non-fat milk powder in TBS.
  • TBS Tween-tris-buffered saline
  • IgE binding patterns from the 39 sera to 6 major NRL antigens, chosen for comparative analysis, are shown in Table 1 and results from immunoblot analyses for 20 sera (10 U.S. and 10 Finnish patients) are compiled in Fig. 1. All but one of the 12 latex allergic spina bifida patients from the U.S. had IgE antibodies binding to at least 2 of the 6 antigens; 5 patient sera recognized all 6 antigens and 9 patient sera reacted with at least 3 antigens (Table 1).
  • a third major antigen in the two patient groups was a 20 kD protein: IgE antibodies against it were recorded in 9/12 U.S. spina bifida patients and in 5/11 Finnish children. Only one of the 5 U.S. health care workers but 8/9 of the Finnish adult latex allergic patients had IgE to the 20 kD antigen. Reactivity patterns with 30, 45 and 75 kD allergens were variable (Table 1) . Three health care worker sera from the U.S. and one Finnish patient with spina bifida showed no anti-latex IgE antibodies in immunoblotting and also all the 21 control sera, including samples from the 3 U.S. spina bifida patients with no findings compatible with latex allergy, gave negative results.
  • SR systemic, non-anaphylactic reaction (incl. generalized urticaria asthma)
  • LR local cutaneous reaction (incl. contact urticaria, eczema, facial oedema)
  • the present immunoblot results showed that the majority (13/15) of latex allergic patients with spina bifida have IgE class antibodies binding to a previously undescribed NRL 27 kD antigen. Also two children (one from the U.S. and one from Finland) with congenital anomalies and histories of multiple operations had anti-27 kD IgE antibodies. Similar IgE antibodies were not detected in adult latex allergic patients from either country or among pediatric patients not having congenital anomalies and histories of multiple operations.
  • IgE antibodies to the 27 kD antigen were not detected in other latex allergic patients from the U.S. or Finland although most of them showed IgE binding to 14 and/or 20 kD NRL antigens. All 21 controls, including 3 spina bifida patients with no evidence of latex allergy, gave negative immunoblot results. This observation suggests that patients with spina bifida or other congenital anomalies who have been subject to multiple operations and other invasive therapeutic procedures may have been exposed to different antigenic source materials than other latex allergic patients.
  • the antigen was prepared by diluting the sap of the latex tree of Malaysia in saline or by extracting latex gloves in buffered saline for 24 hours. Immunization of Mice
  • the spleen was removed aseptically and the cells were mechanically dissociated in RPMI 1640 medium (GIBCO) containing streptomycin (100 ⁇ g/ml) and penicillin (100 units/ml).
  • the red blood cells were lysed with ammonium chloride and the resulting cells were filtered through a nylon membrane. The viability of the cells was determined by trypan blue dye exclusion staining.
  • Spleen cells were then mixed with NS-1 myeloma cells (P3-NSI/Ag4-l) growing at logarithmic phase at a ratio of 4:1. The cells were centrifuged at 500 g for 5 minutes and again washed with RPMI 1640 medium.
  • PEG-1500 polyethylene glycol
  • Sigma polyethylene glycol
  • the cell suspension was gently stirred using the tip of pipet during the addition of PEG.
  • About 20 ml of medium was gradually added (over a 10-minute period) to the cells in order to dilute the PEG.
  • the cells were centrifuged at 500 g for 5 minutes and resuspended in complete RPMI 1640 medium containing glutamine (2 mmol), fetal calf serum (10% v/v), sodium pyruvate (1 mmol), penicillin (100 units/ml) and streptomycin (10 g/ml).
  • the cells were plated in 92-well tissue culture plates in 100 ⁇ l quantities at a concentration of 2.5 x 10 cells/well and incubated in a humidified CO, incubator (5% C0 2 in air) at 37°C. After 24 hours, 100 l of complete medium containing hypoxanthine, aminopterin and thymidine (HAT) was added to each well. Thereafter HAT medium was added to the wells by splitting the medium 1:1 for four consecutive days. Two more HAT changes were made at three-day intervals. After that the cells were grown in hypoxanthine and thymidine medium for the next two weeks with frequent changes of the same medium.
  • hypoxanthine and thymidine thymidine
  • the culture fluids were then tested for antibody-producing hybridomas by BALISA using latex antigen-coated polyvinyl microtiter plates.
  • Wells showing antibody-secreting hybridomas were cloned at least two times by limiting dilution using thymocytes as feeder cells.
  • the purified clones were injected intraperitoneally into pristine-primed syngenic mice for ascitic fluid production. Isotyping
  • the culture fluid and ascites were precipitated with ammonium sulfate (50% saturation).
  • the precipitate was dissolved in a minimal amount of phosphate-buffered saline (PBS) and dialyzed against distilled water at 4°C.
  • PBS phosphate-buffered saline
  • Goat anti-human immunoglobulin classes and subclasses were obtained from commercial sources for isotyping (Bio-Rad, Miles, and Sigma). Microtiter plates were coated with 1:100 to 1:1,000 dilution of goat anti-mouse antibodies in carbonate buffer.
  • the crude latex antigen extract was electrophoresed in sodium dodecyl sulfate (SDS) polyacrylamine gel as described before. A 7.5- to 15% gradient gel was used. About 1 mg of protein was loaded onto a 16 x 16 cm gel and electrophoresed at 30 mA/gel for 2-2.5 hours at 10°C. The proteins from the gels were transferred to nitrocellulose sheets (Bio-Rad) using a semi-dry blotter (Poly Blot, American Bionetics,
  • a sensitive enzyme immunoassay using the biotin and avidin system was used to detect antibodies in the sera. This method has been evaluated extensively in our laboratory for the past several years and has been reported before in detail.
  • the purified antigen was used at a concentration of 25 ng protein/ml for coating the plates. Serum dilutions of 1:100 and 1:1,000 were used to detect specific IgE and IgG.
  • the optical density (OD) values at 490 of crude latex antigens and purified fraction adjusted to the same protein concentration were compared.

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Abstract

L'invention concerne une protéine antigénique du latex de caoutchouc naturel (LCN) de 27 kD pouvant causer de graves réactions allergiques chez les sujets humains sensibilisés au caoutchouc naturel. Cette invention concerne aussi des anticorps et des fragments de ces anticorps qui se lient spécifiquement à cet antigène de LCN de 27 kD. Elle concerne en plus l'utilisation de l'antigène de 27 kD inventé pour détecter des anticorps spécifiques de l'antigène. Des procédés de détection de l'antigène à l'aide d'anticorps spécifiques de cette protéine de 27 kD sont également décrits dans le cadre de cette invention.
PCT/US1994/010226 1993-09-08 1994-09-07 Antigenes du latex de caoutchouc naturel pouvant causer des reactions allergiques Ceased WO1995007298A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU78326/94A AU7832694A (en) 1993-09-08 1994-09-07 Natural rubber latex antigens associated with allergies

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US11759493A 1993-09-08 1993-09-08
US08/117,594 1993-09-08
US18753794A 1994-01-28 1994-01-28
US08/187,537 1994-01-28

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0704457A1 (fr) * 1994-09-16 1996-04-03 The Board Of The Rubber Research Institute Of Malaysia Protéines allergéniques du latex du caoutchouc naturel, leur production et leur utilisation dans les diagnostics
WO2001061305A3 (fr) * 2000-02-15 2002-04-04 Finnish Immunotechnology Ltd Procedes immunochimiques
EP1481991A1 (fr) * 2003-02-28 2004-12-01 Malaysian Rubber Board Protéine allèrgenique de caoutchouc

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
H. ALENIUS ET AL.: "DIFFERENCES IgE REACTIVITY TO LATEX ANTIGENS IN SERA FROM PATIENTS FROM THE US AND FINLAND.", THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 91, no. 1 P2, January 1993 (1993-01-01), ST. LOUIS, MO., US, pages 240 *
H. ALENIUS ET AL.: "IgE REACTIVITY TO 14-kD AND 27-kD NATURAL RUBBER PROTEINS IN LATEX-ALLERGIC CHILDREN WITH SPINA BIFIDA AND OTHER CONGENITAL ANOMALIES.", INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, vol. 102, no. 1, 1993, BASEL, CH, pages 61 - 66 *
H. ALENIUS ET AL.: "LATEX ALLERGY: FREQUENT OCCURRENCE OF IgE ANTIBODIES TO A CLUSTER OF 11 LATEX PROTEINS IN PATIENTS WITH SPINA BIFIDA AND HISTORIES OF ANAPHYLAXIS.", THE JOURNAL OF LABORATORY AND CLINICAL MEDICINE, vol. 123, no. 5, May 1994 (1994-05-01), ST. LOUIS, MO., US, pages 712 - 720 *
R.K. SCOPES: "PROTEIN PURIFICATION, 2nd. EDITION", 1987, SPRINGER-VERLAG, NEW YORK, N.Y., US *
T. PALOSUO ET AL.: "DETECTION OF ANTIGENIC EPITOPES OF THE 27 kD LATEX ALLERGEN IN RUBBER PRODUCTS.", THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 93, no. 1 P2, January 1994 (1994-01-01), ST. LOUIS, MO., US, pages 181 *
V.P. KURUP ET AL.: "CHARACTERIZATION OF A MONOCLONAL ANTIBODY AGAINST LATEX PROTEIN ASSOCIATED WITH LATEX ALLERGY.", THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 92, no. 5, November 1993 (1993-11-01), ST. LOUIS, MO., US, pages 638 - 643 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0704457A1 (fr) * 1994-09-16 1996-04-03 The Board Of The Rubber Research Institute Of Malaysia Protéines allergéniques du latex du caoutchouc naturel, leur production et leur utilisation dans les diagnostics
EP1350798A1 (fr) * 1994-09-16 2003-10-08 The Board Of The Rubber Research Institute Of Malaysia Protéine allergénique hev b III du latex du caoutchouc naturel, sa production et sa utilisation dans les diagnostics
US7576184B2 (en) 1994-09-16 2009-08-18 The Board Of The Rubber Research Institute Of Malaysia Allergenic proteins of natural rubber latex, their production and use in assays
US7994288B2 (en) 1994-09-16 2011-08-09 The Board Of The Rubber Research Institute Of Malaysia Allergenic proteins of natural rubber latex, their production and use in assays
WO2001061305A3 (fr) * 2000-02-15 2002-04-04 Finnish Immunotechnology Ltd Procedes immunochimiques
EP1481991A1 (fr) * 2003-02-28 2004-12-01 Malaysian Rubber Board Protéine allèrgenique de caoutchouc

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