Lentil

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Code: f235
Latin name: Lens esculenta
Source material: Dried seeds
Family: Fabaceae (Leguminosae)
Common names: Lens culinaris, Cicer lens, Lentilla lens

Allergen Exposure

Geographical distribution

Lentils are annuals with flattened edible seeds just a few millimetres in diameter. Lentils were cultivated by the Persians and Egyptians from 2500 BC. Lentils are now cultivated in most warm and subtropical regions of the world. Popular in parts of Europe and a staple throughout much of the Middle East and India, this tiny, lens-shaped, high-protein pulse, said to be the most nutritious of the pulses, has long been used as a meat substitute.

Environment

Lentils are usually dried for storage, transport and sale. They may be used in soups, salads and casseroles, and as dhal, and ground into cereal flour for enriching other flours or infant food. Lentils need to be boiled for 15 minutes to destroy harmful toxins found in the skin.

The young seedpods can be eaten raw or cooked like Green beans. Lentils are more digestible than many legumes. They are high in protein (but low in fat) and have a fair amount of minerals and vitamins.

The seeds are mucilaginous and laxative. They are considered helpful in the treatment of a variety of intestinal afflictions. Made into a paste, they are used as a cleansing application for indolent ulcers.

Allergens

The following allergens have been categorised:

  • Len c 1, a 12 to 16 kDa protein, a major allergen, corresponding to gamma-vicilin storage proteins (1-5).
     
  • Len c 2, a 66 kDa protein, corresponding to seed-specific biotinylated protein (1-2).
     
  • The isoforms Len c 1.0101, Len c 1.0102, Len c 1.0103 and Len c 2.0101 have been characterised.

Both Len c 1 and Len c 2 have been isolated from boiled Lentils. Heat treatment of Lentils was shown to result in drastic changes in the electrophoretic pattern, a strong increase of low-molecular-weight bands of 12 to 16 kDa proteins, and a decrease or disappearance of protein bands in the 25 to 45 kDa range. Len c 1 was shown to bind to 68% of the individual sera of Lentil-allergic individuals tested, whereas Len c 2 reacted with 41% of individual sera of this group (1).

Len c 1.01, a 48 kDa protein, has been characterised. Two of its processing fragments, corresponding to subunits of 12 to 16 kDa (previously named Len c 1) and 26 kDa, were shown to also be relevant Lentil IgE-binding proteins. The purified allergen was recognised by 77% (17/22) of the individual sera from patients with Lentil allergy. Three isoforms were isolated, varying in their degree of N-glycosylation. There was a greater than 50% amino acid homology with Peanut and Soy vicillins (5).

Although many legumes appear to have both heat-labile and heat-stable allergens, a common feature of most legume allergens is their natural resistance to thermal, chemical, and, in some respects, proteolytic denaturation (6). The process of heating results in a significant decrease in IgE antibody binding, and IgE inhibition studies showed that the boiled Lentil extract had a greater inhibitory capacity than the crude extract. Immunoblots revealed no important differences in IgE binding patterns between the 2 extracts. Multiple allergens have been detected in a wide range of molecular mass, and boiled Lentil extracts maintained strong allergenicity (7). But further evidence for the heat alteration of the allergenicity was demonstrated in studies that concluded that Lentil extracts for the diagnosis of Lentil hypersensitivity should be heated, since these best identify clinically sensitive individuals (8).

Lentil-allergic patients who had developed a tolerance to Lentil ingestion were shown to have lower IgE antibody levels than symptomatic patients (7).

A lipid transfer protein has been isolated from germinated Lentil seed (9). Its potential allergenicity was not evaluated.

Potential cross-reactivity

An extensive cross-reactivity among the different individual species of the genus could be expected but in fact is not seen frequently (10). In an in vitro study, the IgE antibody binding by protein extracts of 11 food legumes was examined by IgE antibody determination and RAST inhibition. Cross-allergenicity was demonstrated to be immunochemically frequent, and most marked between the extracts of Peanut, Garden pea, Chick pea, and Soybean (11). However, clinical studies have found that there is little cross-reactivity among members of the legume family (12-14).

In contrast with the typical diet of most other Western countries, legumes are an important ingredient in the Mediterranean diet, and it is therefore not surprising that among Spanish children, sensitivity to legumes is the fifth most prevalent food allergy. Lentil and Chick pea are the most frequent causes of allergic reactions to legumes in Spanish children. Legumes have structurally homologous proteins, but they are not all equally allergenic. In vitro and in vivo tests may not predict cross-reactivity or clinical relevance. In a study of 39 Spanish children challenged (open or simple blind) with 2 or more legumes, the majority had symptoms with more than 1 legume. Thirty-two (82%) reacted to 2 or more legumes: 43,5% to 3, 25,6% to 2, and 13% to 4 legumes. Seventy-three per cent of the patients challenged with Lentil and Pea had positive challenges to both, 69,4% to Lentil and Chick pea, 60% to Chick pea, and 64,3% to Lentil, Chick pea and Pea simultaneously. Peanut allergy can be associated with allergy to Lentil, Chick pea and Pea, but less frequently. In contrast, White bean, Green bean and Soy were well tolerated by children allergic to other legumes. A high degree of cross-reactivity appeared to exist among Lentil, Chick pea, Pea and Peanut, on evidence from inhibition experiments. In this study, 82% of the children allergic to legumes were also sensitised to pollen. Pea and Bean were more likely to have in vitro cross-reactivity with Lolium perenne, Olea europea and Betula alba; the authors suggested that this was a result of common antigenic determinants or the coexistence of pollen and legume allergy (15).

Similarly, in another Spanish study, symptomatic hypersensitivity to Chick pea was frequently associated with Lentil allergy (16). Cross-reactivity or co-sensitivity was also observed among Blue vetch (Chickling pea), Chick pea, and Lentil (17). Similarly, shared allergenicity has been shown among blackgram, Lentil, Lima bean and Pea (18).

Panallergens or common protein families (e.g., vicilins) may result in cross-reactivity among foods. Amino acid sequences deduced from 2 clones of the Lentil allergen Len c 1.02 were shown to have greater than 50% identity with the major Peanut allergen Ara h 1, and with Soybean (conglutinin subunits), which are allergens belonging to the vicilin family (5). Similarly, in a study of 18 Spanish patients with Pea allergy, allergic reactions to ingestion of Pea were frequently associated with Lentil allergy. Vicilin and convicilin were shown to be potential major allergens from Pea, and these cross-reacted with the major Lentil allergen Len c 1 (4). Similarly, analysis of the epitopes and vicilin allergens Ara h 1 from Peanut, Len c 1 from Lentil, and Pis s 1 from Pea were shown to be similar, readily accounting for the IgE-binding cross-reactivity commonly observed among the vicilin allergens from these edible legume seeds (3).

Clinical Experience

IgE-mediated reactions

Lentil is the most common legume implicated in allergic reactions in food-allergic paediatric patients in the Mediterranean area and in many Asian communities. Approximately 20% of patients allergic to these legumes present with severe and systemic symptoms, although isolated cutaneous reactions are most common (5). Lentils are ranked fourth as a cause of hypersensitivity reactions in Spanish children, fifth in India. There are several reports in the literature of allergic symptoms caused by Lentil (8,19-20). In a Spanish study, 10,1% of 355 paediatric patients with food allergy had a convincing history of allergy to Lentils, and urticaria and oral allergy syndrome (OAS) were the most frequent symptoms. The symptoms may develop after ingestion of cooked Lentil and/or after inhalation of steam from boiling Lentil. Symptoms include angioedema, urticaria, asthma and anaphylaxis (1,16).

In a Spanish study, in 20 of 22 subjects who experienced allergy symptoms following exposure to Lentil, the most frequent symptoms were oropharyngeal ones (40%) and acute urticaria (30%); 3 patients also reported symptoms when they were exposed to steam from cooked Lentil. Onset of sensitisation occurred at less than 4 years of age, and 9 patients had allergic reactions to other legumes: Chick pea (6 patients), Pea (2 patients), and Green bean (1 patient) (21). Similar symptoms, i.e., urticaria, angioedema, abdominal symptoms, rhinoconjunctivitis and asthma, following ingestion or inhalation of vapours from cooked legumes (Lentil, Bean or Chick pea) have been reported, but Lentil was found to induce the most severe reactions (22).

In an Indian study based in Delhi, the relevance of serum total and IgE antibodies was investigated in asthmatics with food sensitisation. Out of 216 consecutive patients, 172 were found to have elevated serum total IgE. Rice elicited marked positive skin prick test reactions (SPT) in 24 (11%) asthma patients, followed by Blackgram with 22 (10%), Lentil with 21 (9.7%) and Citrus fruits with 20 (9.2%) (23).

Four episodes of anaphylaxis occurred in an 8-year-old girl, which could be attributed to Lentil. These episodes occurred between the ages of 3 and 7 years. The first 3 involved ingestion of cooked Lentil and each episode required smaller amounts to induce symptoms. The fourth episode occurred with exposure by inhalation to cooking Lentil soup. Skin reactivity and serum IgE antibodies to Lentil were confirmed (24). Severe reactions may occur in adults. A 20-year-old man experienced episodes of asthma when exposed to the steam from cooking either Chick pea or Lentil. Type I hypersensitivity was demonstrated by means of serum IgE, skin reactivity, histamine release tests, and RAST inhibition. Specific bronchial challenges with the heated (75 °C for 30 minutes) extracts of Chick pea and Lentil elicited an immediate response (25).

Other reactions

Infantile food protein-induced enterocolitis syndrome (FPIES) is a severe cell-mediated gastrointestinal food hypersensitivity typically provoked by Cow's milk or Soy. A study reported on other foods causing this syndrome: 14 infants with FPIES caused by grains (Rice, Oat, and Barley), vegetables (Sweet potato, Squash, String beans, Pea), or poultry (Chicken and Turkey) were identified. Symptoms of typical FPIES are delayed (median: 2 hours) and include vomiting, diarrhoea, and lethargy/dehydration. Eleven infants (78%) reacted to >1 food protein, including 7 (50%) who reacted to >1 grain. Nine (64%) of all patients with solid food FPIES also had Cow's milk and/or Soy FPIES. Initial presentation was severe in 79% of the patients, prompting sepsis evaluations (57%) and hospitalisation (64%) for dehydration or shock. None of the patients developed FPIES to maternally ingested foods while breastfeeding unless the causal food was fed directly to the infant. (26)  Similarly, 6 patients (4 males, 2 females, aged 3-12 months) were diagnosed with FPIES triggered by foods other than Cow's milk and Soy: Chicken in 4, Turkey in 2, Pea in 1, and Lentils in 1. (Five patients reacted to more than 1 food type.) All reactions developed within 2 hours of ingestion of the allergenic food (27).

If Lentils are to be eaten whole, they must be boiled an extra 15 minutes to destroy harmful toxins found in the skins.

Aspiration of leguminous vegetables can cause a granulomatous pneumonitis, know as Lentil aspiration pneumonia, that manifests on radiological studies with small, poorly defined nodular opacities (28).

The Lentil pest Bruchus lentis was reported to have resulted in occupational asthma in an agronomist (29). In a more recent study of 16 patients with asthma and anaphylaxis as a result of inhalation of Lentil particles or ingestion of Lentils, SPT was positive to infested Lentils and B. lentis in all patients and negative to noninfested Lentil extracts. Five asthmatic patients were positive on bronchial challenge tests for Bruchus extract. Oral challenges performed with boiled infested Lentils were positive in 6 of 7 patients. These patients had no IgE antibodies to Lentil-specific proteins. The Lentil pest B. lentis can therefore be a cause of IgE-mediated rhinoconjunctivitis and asthma in patients eating or inhaling infested Lentil particles (30).

Compiled by Dr Harris Steinman, harris@zingsolutions.com

References

  1. Sanchez-Monge R, Pascual CY, Diaz-Perales A, Fernandez-Crespo J, Martin-Esteban M, Salcedo G. Isolation and characterization of relevant allergens from boiled lentils.
    J Allergy Clin Immunol 2000;106(5):955-61
  2. International Union of Immunological Societies Allergen Nomenclature: IUIS official list http://www.allergen.org/List.htm 2007
  3. Barre A, Borges JP, Rougé P. Molecular modelling of the major peanut allergen Ara h 1 and other homotrimeric allergens of the cupin superfamily: a structural basis for their IgE-binding cross-reactivity.
    Biochimie 2005;87(6):499-506
  4. Sanchez-Monge R, Lopez-Torrejon G, Pascual CY, Varela J, Martin-Esteban M, Salcedo G. Vicilin and convicilin are potential major allergens from pea.
    Clin Exp Allergy 2004;34(11):1747-53
  5. Lopez-Torrejon G, Salcedo G, Martin-Esteban M, Diaz-Perales A, Pascual CY, Sanchez-Monge R. Len c 1, a major allergen and vicilin from lentil seeds: protein isolation and cDNA cloning. J Allergy Clin Immunol 2003;112(6):1208-15
  6. Lalles JP, Peltre G. Biochemical features of grain legume allergens in humans and animals. Nutr Rev 1996;54(4 Pt 1):101-7
  7. Ibanez Sandin D, Martinez San Ireneo M, Maranon Lizana F, Fernandez-Caldas E, Alonso Lebrero E, Laso Borrego T. Specific IgE determinations to crude and boiled lentil (Lens culinaris) extracts in lentil-sensitive children and controls.
    Allergy 1999;54(11):1209-14
  8. Martinez San Ireneo M, Ibanez Sandin MD, Fernandez-Caldas E, Maranon F, Munoz Martinez MC, Laso Borrego MT. The diagnostic value of crude or boiled extracts to identify tolerant versus nontolerant lentil-sensitive children. Ann Allergy Asthma Immunol 2001;86(6):686-90
  9. Finkina EI, Balandin SV, Serebryakova MV, Potapenko NA, Tagaev AA, Ovchinnikova TV. Purification and primary structure of novel lipid transfer proteins from germinated lentil (Lens culinaris) seeds.
    Biochemistry (Mosc) 2007;72(4):430-8
  10. Yman L. Botanical relations and immuno-logical cross-reactions in pollen allergy. 2nd ed. Pharmacia Diagnostics AB. Uppsala. Sweden. 1982: ISBN 91-970475-09
  11. Barnett D, Bonham B, Howden ME. Allergenic cross-reactions among legume foods – an in vitro study.
    J Allergy Clin Immunol 1987;79(3):433-8
  12. Bernhisel Broadbent J, Sampson HA. Cross-allergenicity in the legume botanical family in children with food hypersensitivity.
    J Allergy Clin Immunol 1989;83:435-40
  13. Bernhisel-Broadbent J, Taylor S, Sampson HA. Cross-allergenicity in the legume botanical family in children with food hypersensitivity. II. Laboratory correlates. J Allergy Clin Immunol 1989;84(5 Pt 1):701-9
  14. Eigenmann PA, Burks AW, Bannon GA, Sampson HA. Identification of unique peanut and soy allergens in sera adsorbed with cross-reacting antibodies. J Allergy Clin Immunol 1996;98(5 Pt 1):969-78
  15. Ibanez MD, Martinez M, Sanchez JJ, Fernandez-Caldas E. Legume cross-reactivity. [Spanish] Allergol Immunopathol (Madr) 2003;31(3):151-61
  16. Pascual CY, Fernandez-Crespo J, Sanchez Pastor S, Ayuso R, Garcia Sanchez G, Martin-Esteban M. Allergy to lentils in Spain. Pediatr Pulmonol 2001;Suppl 23:41-3
  17. Huertas AJ, Iriarte P, Polo P, Ayuso R. Urticaria during prick by prick skin test with legumes. [Abstract] Allergy 1995;50S:230
  18. Kumari D, Kumar R, Sridhara S, Arora N, Gaur SN, Singh BP. Sensitization to blackgram in patients with bronchial asthma and rhinitis: clinical evaluation and characterization of allergens.
    Allergy 2006;61(1):1-110
  19. Sainza T, Zapatero L, Martinez MI, Lozano M, Zubeldia JM, Baera ML. Hypersensitivity to Lathyrus sativus. [Abstract] Allergy 1995;50S:230
  20. Moroz LA, Yang WH. Kunitz soybean trypsin inhibitor: a specific allergen in food anaphylaxis. N Engl J Med 1980;302(20):1126-8
  21. Pascual CY, Fernandez-Crespo J, Sanchez-Pastor S, Padial MA, Diaz-Pena JM, Martin-Munoz F, Martin-Esteban M. Allergy to lentils in Mediterranean pediatric patients. J Allergy Clin Immunol 1999;103(1 Pt 1):154-8
  22. Carrillo Diaz T, Cuevas Agustin M, et al.
    In vitro immunologic diagnosis of hypersensitivity to vegetables [Spanish]. Allergol Immunopathol 1986;14(2):139-46
  23. Kumar R, Singh BP, Srivastava P, Sridhara S, Arora N, Gaur SN. Relevance of serum IgE estimation in allergic bronchial asthma with special reference to food allergy. Asian Pac J Allergy Immunol 2006;24(4):191-9
  24. Kalogeromitros D, Armenaka M, Galatas I, Capellou O, Katsarou A. Anaphylaxis induced by lentils. Ann Allergy Asthma Immunol 1996;77(6):480-2
  25. Martin JA, Compaired JA, de la Hoz B, Quirce S, Alonso MD, Igea JM, Losada E. Bronchial asthma induced by chick pea and lentil. Allergy 1992;47(2 Pt 2):185-7
  26. Nowak-Wegrzyn A, Sampson HA, Wood RA, Sicherer SH. Food protein-induced enterocolitis syndrome caused by solid food proteins.
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  27. Levy Y, Danon YL. Food protein-induced enterocolitis syndrome - not only due to cow's milk and soy. Pediatr Allergy Immunol 2003;14(4):325-9
  28. Marom EM, McAdams HP, Sporn TA, Goodman PC. Lentil aspiration pneumonia: radiographic and CT findings. J Comput Assist Tomogr 1998;22(4):598-600
  29. Armentia A, Lombardero M, Barber D, Castrodeza J, Calderon S, Gil FJ, Callejo AM. Occupational asthma in an agronomist caused by the lentil pest Bruchus lentis. Allergy 2003;58(11):1200-1
  30. Armentia A, Lombardero M, Blanco C, Fernandez S, Fernandez A, Sanchez-Monge R. Allergic hypersensitivity to the lentil pest Bruchus lentis. Allergy 2006;61(9):1112-6

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.