Abstract for Plenary Talk 6.2

 

 

25 Years of Natural Rubber Latex Allergy: From Diagnostics to Prevention and Immunotherapy

T. Palosuo, National Public Health Institute, Helsinki, Finland

Prevalence and clinical manifestations

Immediate allergic reactions to natural rubber latex (NRL) have now been recognized for 25 years. An important source of sensitization has been considered to be proteins or peptides eluting from protective NRL gloves. Prevalence studies, based on skin prick testing (SPT), indicate that 3 to 17% of exposed health care workers are sensitized to NRL whereas the sensitization rate in the general population is less than 1 %. Although accumulating evidence suggests that the peak of the “epidemic” may already have been passed several unanswered questions still exist. From the practical point of view, NRL allergy is one of the most frequently encountered occupational diseases among health care workers (HCW) and, proportionally, a gradually increasing problem in other occupations where protective gloves are used.

Today the majority of NRL-allergic patients do not belong to the traditional risk groups (like HCW and children with spina bifida) but are rather normal individuals, usually atopic, who are frequently in contact with NRL products. Importantly also, NRL allergens become easily airborne with glove powder and may cause occupational asthma in persons sensitized to NRL. NRL-allergic patients also frequently show allergy to various fruits, such as banana, avocado, chestnut, and kiwi. The condition, known as “latex-fruit-syndrome”, appears to be caused by allergic cross-reactions.

Diagnosis

Positive SPT reaction (preferably using standardized reagents) and/or demonstration of circulating IgE-antibodies to NRL allergens with concordant clinical histories often confirms NRL allergy. In case of discrepancy between symptoms and SPT or specific IgE results a use (challenge) test with latex gloves or pulmonal inhalation tests has to be considered, provided that the patient does not have a history of NRL-related anaphylaxis. Diagnostic procedures would obviously benefit from the use of purified allergens as test reagents instead of poorly characterized extracts; however, such reagents are not yet commercially available.

NRL allergens

The liquid latex from the rubber tree, Hevea brasiliensis, contains more than 250 proteins or polypeptides, 50-60 of which show allergenic potential. After discovering the first NRL allergen, the rubber elongation factor (REF or Hev b1) in 1993 by Czuppon and co-workers, several additional NRL allergens have been identified and characterized. The WHO/IUIS Allergen Nomenclature Sub-Committee currently (March 2005) lists 13 latex allergens characterized at the molecular level (www.allergen.org), most of which have been cloned and produced by recombinant DNA techniques. Of them two allergens, hevein (Hev b6.02) and Hev b5, are considered as the most important allergens for adults. Allergic cross-reactivity in NRL allergy also continues to be of great interest and it was recently shown that well-conserved hevein-like domains in tropical fruits could be responsible for a major part of such reactions.

Allergens in manufactured NRL products

A relatively limited number of allergens have so far been unequivocally demonstrated in manufactured NRL products. Two major NRL allergens, Hev b6.02 and Hev b5, have regularly been demonstrated in abundant amounts in highly allergenic gloves and are likely to be responsible for a major proportion of both sensitization and clinical reactions. Interestingly, two hydrophobic allergens, i.e, Hev b1 and Hev b3, associated with NRL allergy in children with spina bifida and multiple surgical procedures, are also often found in highly allergenic NRL gloves. Sensitive and specific immunoassays to quantify NRL allergens in manufactured products have been developed in the past few years but a major question remains that, with the exception of Hev b 6.02., the molecular forms of allergens or their fragments residing in rubber products are not known.

Prevention

Avoiding exposure to NRL allergens has been considered as the only effective means for the prevention of sensitization. Due to the ubiquity of NRL products in the normal environment this goal is obviously difficult to reach. Substantial reductions in NRL allergen exposure may, however, be achieved by the use of low-allergen NRL gloves and also avoiding powdered gloves that often have high allergen contents. Measures taken in health care in some countries to reduce exposure to medical NRL products seem to be effective in decreasing the number of new sensitizations. Similar steps should be taken in the non-medical field as well.

Immunotherapy

Preliminary reports of latex-specific immunotherapy with promising results have been reported. NRL extracts seem to be effective but their use is hampered by serious side effects, including systemic and anaphylactic reactions. Alternatives include the use of latex peptides or genetically engineered “hypoallergenic” proteins which do not bind IgE but initiate normal immune responses at T-cell level. Knowledge of IgE-binding structures on the surface of allergens, i.e. conformational epitopes, is required for the design of strategies for allergen-specific immunotherapy. Pilot experiments with such reagents using animal models of latex allergy are currently in progress.

Future prospects

More thorough knowledge of NRL allergens and their clinical significance is expected to help researchers to develop more specific in vivo and in vitro tests for diagnostic purposes while the production of modified allergens could provide new tools for immunotherapy. Standardization authorities in the U.S. (ASTM) and in Europe (CEN) are working to set up acceptable limits for latex allergens in medical gloves aiming at reduced exposure and thereby reduced sensitization. Substantial progress in this field is anticipated to be seen within the next few years.

 

Content last modified: 3 April 2005