Latin name: Bacillus licheniformis
Common names: Maxatase
An occupational allergen, which may frequently induce hayfever, asthma and conjunctivitis in sensitised individuals.
Subtilisins are proteolytic enzymes of bacterial origin used in the manufacture of washing detergents. Maxatase is one of these enzymes; Alcalase, Esperase and Savinase are 3 others. These enzymes may also be found in various foods.
The enzymes are all produced using species of Bacillus. Maxatase and Alcalase (which have sometimes been considered virtually interchangeable) come from B. licheniformis, Esperase from an alkalophilic strain of a B. licheniformis, and Savinase from an alkalophilic strain of B. amyloliquefaciens (a mistaken attribution is often to B. subtilis). Alcalase and Maxatase are usually found in washing detergents recommended for use at 10 to 65°C and pH 7 to10.5. Savinase and Esperase may be used at up to pH 11 and 12, respectively.
Other enzymes used in washing detergents are the a-amylase enzymes, e.g., Termamyl, an enzyme also derived from B. licheniformis. This enzyme is also used in the production of glucose syrups. The a-amylase enzymes are particularly useful in dishwashing and de-starching detergents.
These enzymes are high-molecular-weight antigens and have been implicated in allergic rhinitis and asthma.
No allergens from this substance have yet been characterised.
In a group of detergent enzyme workers with known exposure to Alcalase/Maxatase, sensitisation to Savinase, another microbial protease, to which there was no previous occupational exposure, was demonstrated by skin-specific IgE. The researchers attributed this to either cross-reactivity between these enzymes or to foreign enzyme contaminants contained in the Savinase antigen (1).
Since the 1960s an increasing number of occupational allergies against natural and against modified recombinant enzymes has been reported. Subtilisins, enzymes frequently used in the manufacture of washing detergents, have been shown to cause allergic reactions, in particular airway sensitisation. Symptoms, results of skin prick tests, detection of specific IgE antibodies, and results of specific bronchoprovocation tests have confirmed an immunologic mechanism to these high-molecular-weight antigens (2-11). Those affected are mainly workers in the detergent industry rather than consumers (12-15).
Not all the enzymes are equipotent in their ability to induce allergic sensitisation. In guinea pig models, Termamyl was about 10-fold more potent than Alcalase/Maxatase, and the protease subtilisin B was shown to be less potent. Another protease, Savinase, was shown to be equivalent in potency to Alcalase/Maxatase. Prospective evaluation of skin-specific IgE tests of factory workers showed that sensitisations to Termamyl and Savinase were similar to sensitisations to Alcalase. The sensitisations to subtilisin B were weaker than those to Alcalase (16).
A close relationship has been described between bronchial hyperresponsiveness and the provocation dose of the enzyme. Researchers have reported that bronchopulmonary testing with solutions of the enzyme is highly sensitive and specific in confirming the diagnosis of occupational asthma due to these proteolytic enzymes (11).
In the majority of studies, sensitisation to Maxatase necessitated further avoidance of these enzymes. Contrary to these findings, in a study conducted over a 7-year period, only 3 respiratory adverse effects (all rhinitis) were reported, the authors stating that employees with positive skin prick tests can continue to work (16).
Specific IgE tests have been reported to be very useful in the diagnosis of sensitisation to these enzymes (12).
A 53-year-old woman developed respiratory symptoms while working with a cleaner containing subtilisins. Her symptoms intensified in the work environment and improved away from work. Computed tomography demonstrated alveolar and interstitial infiltrates with subsequent scarring. Pulmonary function showed a restrictive pattern with diminished diffusion capacity. Bronchoalveolar lavage showed lymphocytosis, and all cultures were negative. Precipitating antibodies to the enzyme were found in the patient's serum. These findings supported a diagnosis of extrinsic allergic alveolitis from the enzyme contained in the cleaner (17).
- Bernstein DI, Bernstein IL, Gaines WG Jr, Stauder T, Wilson ER. Characterization of skin prick testing responses for detecting sensitization to detergent enzymes at extreme dilutions: inability of the RAST to detect lightly sensitized individuals. J Allergy Clin Immunol. 1994;94(3 Pt 1):498-507
- Reinheimer W, Utz G. Allergic asthma due to the detergent additive maxatase. [German] Dtsch Med Wochenschr. 1971 Feb 5;96(6):246-7
- Mitchell CA, Gandevia B. Acute bronchiolitis following provocative inhalation of "alcalase"-a proteolytic enzyme used in the detergent industry. Med J Aust. 1971;1(26):1363-7
- Little DC, Dolovich J. Respiratory disease in industry due to B. subtilis enzyme preparations. Can Med Assoc J. 1973;108(9):1120-5
- Cernelc D, Jurc F, Cernelc P, Gabrovsek P, Gabrovsek L. Clinical and immunological effect of washing powder enzymes on workers and users (author's transl). [German] Allerg Immunol (Leipz). 1977;23(3):185-92
- Zetterstrom O. Challenge and exposure test reactions to enzyme detergents in subjects sensitized to subtilisin. Clin Allergy. 1977;7(4):355
- van Kampen V, Merget R. Occupational airway sensitization due to subtilisin. [German] Pneumologie. 2002;56(3):182-6
- Kempf W, Oman H, Wuthrich B. Allergy to proteases in medical laboratory technicians: A new occupational disease? J Allergy Clin Immunol. 1999;104(3 Pt 1):700-1
- Lemiere C, Cartier A, Dolovich J, Malo JL. Isolated late asthmatic reaction after exposure to a high-molecular-weight occupational agent, subtilisin. Chest. 1996;110(3):823-4
- Perdu D, Lavaud F, Cossart C, Legrele S, Passemard F, Deltour G, Dubois de Montreynaud JM. Detergent enzymes: has the risk of occupational sensitization disappeared? [French] Rev Mal Respir. 1992;9(4):443-8
- Paggiaro P, Pardi F, Amram D, Bacci E, Ferrante B, Baschieri L. Validity of a specific bronchial provocation test with proteolytic enzymes in occupational bronchial asthma caused by enzymatic detergents. [Italian] G Ital Med Lav. 1984;6(5-6):201-4
- Pepys J, Wells ID, D'Souza MF, Greenberg M. Clinical and immunological responses to enzymes of Bacillus subtilis in factory workers and consumers. Clin Allergy. 1973;3(2):143-60
- Valer M. Skin irritancy and sensitivity to laundry detergents containing proteolytic enzymes. Part II. Berufsdermatosen. 1975;23(3):96-115
- Simesen B, Wide L, Zachariae H. Prick- and radioallergsorbent tests (RAST) to Alcalase in a population not exposed to enzyme detergents. Acta Allergol. 1976;31(1):71-7
- Zachariae H, Hoech-Thomsen J, Witmeur O, Wide L. Detergent enzymes and occupational safety. Observations on sensitization during Esperase production. Allergy. 1981;36(7):513-6
- Sarlo K, Fletcher ER, Gaines WG, Ritz HL. Respiratory allergenicity of detergent enzymes in the guinea pig intratracheal test: association with sensitization of occupationally exposed individuals. Fundam Appl Toxicol. 1997;39(1):44-52
- Tripathi A, Grammer LC. Extrinsic allergic alveolitis from a proteolytic enzyme. Ann Allergy Asthma Immunol. 2001;86(4):425-7