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Background: The Non-Celiac Gluten Sensitivity (NCGS) is a category inside the Gluten-Related Disorders (GRD) that groups the patients with unidentified mechanisms responsible for their symptoms.

Objective: To evaluate the opportunity of an ex vivo challenge immunoassay, the Leukocyte Adherence Inhibition Test (LAIT), to discriminate non—IgE-mediated gluten-specific immunoreactivity in patients with NCGS.

Methods: Ex vivo challenge tests performed with gluten latex extract, monitored by LAIT, were assayed in an asymptomatic control group of 30 individuals and a group of 52 patients with GRD not related to any identifiable immune mechanism (NCGS).

Results: The mean Leukocyte Adherence Inhibition (LAI) of the control group was 10.9%. The mean LAI of the NCGS patients’ group was 54.9%. The non-parametric Wilcoxon-Mann-Whitney U test comparing the control group with the NCGS patient’s group showed significance with a p-value < 0.00001.

Conclusion: The LAIT is an ex vivo challenge test able to discriminate gluten-sensitive and gluten-tolerant individuals, suggesting the participation of an immune Non—IgE-mediated hypersensitivity reaction in patients with the clinical diagnosis of NCGS.

References

  1. Wieser H. Chemistry of gluten proteins. Food Microbiol. 2007;24(2):115-9.
     Google Scholar
  2. Biesiekierski JR. What is gluten? J Gastroenterol Hepatol. 2017; 32 Suppl 1: 78-81.
     Google Scholar
  3. Shewry PR, Tatham AS. The prolamin storage proteins of cereal seeds: structure and evolution. The Biochemical Journal. 1990; 267(1): 1-12.
     Google Scholar
  4. Nadeem M, Anjum FM, Khan MR, Sajjad M, Hussain S, Arshad MS. Electrophoretic Characteristics of Gluten Proteins as Influenced by Crop Year and Variety. International Journal of Food Properties. 2016; 19(4): 897-910.
     Google Scholar
  5. Zhou Z, Zhang Z, Jia L, Qiu H, Guan H, Liu C, et al. Genetic Basis of Gluten Aggregation Properties in Wheat (Triticum aestivum L.) Dissected by QTL Mapping of GlutoPeak Parameters. Front Plant Sci. 2021; 11(2252).
     Google Scholar
  6. Vaclavik VA, Christian EW. Grains - Composition of cereal grains. Essentials of food science. Chapter 6: Springer; 2014: 63-82.
     Google Scholar
  7. Tilley M, Chen YR, Miller RA. 9 - Wheat breeding and quality evaluation in the US. Breadmaking (Second Edition): Woodhead Publishing; 2012: 216-36.
     Google Scholar
  8. Amoriello T, Turfani V, Carcea M. Durum wheat semolina gluten content predicted by means of GlutoPeak parameters. Proceedings of the 10th AISTEC Conference “Grains for Feeding the World”; Milan - Italy, 2015.
     Google Scholar
  9. Vaclavik VA, Christian EW. Baked products. Essentials of food science: Springer; 2014: 299-322.
     Google Scholar
  10. Ferrari MC, Clerici MTPS, Chang YK. A comparative study among methods used for wheat flour analysis and for measurements of gluten properties using the Wheat Gluten Quality Analyser (WGQA). Food Science and Technology. 2014; 34(2): 235-42.
     Google Scholar
  11. Chirdo FG, Rumbo M, Añón MC, Fossati CA. Presence of High Levels of Non-Degraded Gliadin in Breast Milk from Healthy Mothers. Scandinavian Journal of Gastroenterology. 1998; 33(11): 1186-92.
     Google Scholar
  12. Al-Toma A, Volta U, Auricchio R, Castillejo G, Sanders DS, Cellier C, et al. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterology Journal. 2019; 7(5): 583-613.
     Google Scholar
  13. Asri N, Rostami-Nejad M. Chapter 4 - Gluten-related disorders definition. Gluten-Related Disorders: Academic Press; 2022: 49-57.
     Google Scholar
  14. Cabanillas B. Gluten-related disorders: Celiac disease, wheat allergy, and nonceliac gluten sensitivity. Critical Reviews in Food Science and Nutrition. 2020; 60(15): 2606-21.
     Google Scholar
  15. Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med. 2012; 10: 13.
     Google Scholar
  16. Taraghikhah N, Ashtari S, Asri N, Shahbazkhani B, Al-Dulaimi D, Rostami-Nejad M, et al. An updated overview of spectrum of gluten-related disorders: clinical and diagnostic aspects. BMC Gastroenterol. 2020; 20(1): 258.
     Google Scholar
  17. Gell PGH, Coombs RRA. Classification of Allergic Reactions Responsible for Clinical Hypersensitivity and Disease. Clinical Aspects of Immunology. 2nd ed. Oxford: Blackwell Scientific Publications; 1968: 575-96.
     Google Scholar
  18. Hadjivassiliou M, Sanders DS, Woodroofe N, Williamson C, Grünewald RA. Gluten ataxia. Cerebellum. 2008; 7(3): 494-8.
     Google Scholar
  19. Alvey C, Anderson CM, Freeman M. Wheat gluten and coeliac disease. Arch Dis Child. 1957; 32(165): 434-7.
     Google Scholar
  20. Plotnikova N, Miller JL. Dermatitis herpetiformis. Skin Therapy Letter. 2013; 18(3): 1-3.
     Google Scholar
  21. Wolters VM, Wijmenga C. Genetic background of celiac disease and its clinical implications. Am J Gastroenterol. 2008; 103(1): 190-5.
     Google Scholar
  22. Hunt KA, Zhernakova A, Turner G, Heap GA, Franke L, Bruinenberg M, et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet. 2008; 40(4): 395-402.
     Google Scholar
  23. Tatham AS, Shewry PR. Allergens to wheat and related cereals. Clin Exp Allergy. 2008; 38(11): 1712-26.
     Google Scholar
  24. Varjonen E, Vainio E, Kalimo K. Antigliadin IgE-ndicator of wheat allergy in atopic dermatitis. Allergy. 2000; 55(4): 386-91.
     Google Scholar
  25. Sugiyama A, Kishikawa R, Honjo S, Nishie H, Iwanaga T, Furue M. Anti-gluten IgE titer is associated with severity of provocation test-evoked symptoms in wheat-dependent exercise-induced anaphylaxis. Allergol Int. 2019; 68(4): 541-3.
     Google Scholar
  26. Pastorello EA, Toscano A, Scibilia G, Stafylaraki C, Rossi CM, Borgonovo L, et al. Clinical Features of Wheat Allergy Are Significantly Different between Tri a 14 Sensitized Patients and Tri a 19 Sensitized Ones. International Archives of Allergy and Immunology. 2021.
     Google Scholar
  27. Mäkelä MJ, Eriksson C, Kotaniemi-Syrjänen A, Palosuo K, Marsh J, Borres M, et al. Wheat allergy in children – new tools for diagnostics. Clinical & Experimental Allergy. 2014; 44(11): 1420-30.
     Google Scholar
  28. Qiu C, Zhong L, Huang C, Long J, Ye X, Wu J, et al. Cell-bound IgE and plasma IgE as a combined clinical diagnostic indicator for allergic patients. Scientific Reports. 2010; 10(1): 4700.
     Google Scholar
  29. Aguilera-Lizarraga J, Florens MV, Viola MF, Jain P, Decraecker L, Appeltans I, et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature. 2021; 590(7844): 151-6.
     Google Scholar
  30. Ogino R, Chinuki Y, Yokooji T, Takizawa D, Matsuo H, Morita E. Identification of peroxidase-1 and beta-glucosidase as cross-reactive wheat allergens in grass pollen-related wheat allergy. Allergology International. 2021; 70(2): 215-22.
     Google Scholar
  31. Pastorello EA, Farioli L, Conti A, Pravettoni V, Bonomi S, Iametti S, et al. Wheat IgE-Mediated Food Allergy in European Patients: α-Amylase Inhibitors, Lipid Transfer Proteins and Low-Molecular-Weight Glutenins. Int Arch Allergy Immunol. 2007; 144(1): 10-22.
     Google Scholar
  32. Cianferoni A. Wheat allergy: diagnosis and management. J Asthma Allergy. 2016; 9: 13-25.
     Google Scholar
  33. Allardyce RA, Shearman DJ. Leukocyte reactivity to alpha-gliadin in dermatitis herpetiformis and adult coeliac disease. Int Arch Allergy Appl Immunol. 1975; 48(3): 395-400.
     Google Scholar
  34. Kieffer M. Serum antibodies to gliadin and other cereal proteins in patients with coeliac disease and dermatitis herpetiformis. Dan Med Bull. 1985; 32(5): 251-62.
     Google Scholar
  35. Ferguson A, Carswell F. Precipitins to dietary proteins in serum and upper intestinal secretions of coeliac children. Br Med J. 1972; 1(5792): 75-7.
     Google Scholar
  36. Losurdo G, Principi M, Iannone A, Amoruso A, Ierardi E, Di Leo A, et al. Extra-intestinal manifestations of non-celiac gluten sensitivity: An expanding paradigm. World J Gastroenterol. 2018; 24(14): 1521-30.
     Google Scholar
  37. Catassi C, Bai JC, Bonaz B, Bouma G, Calabrò A, Carroccio A, et al. Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders. Nutrients. 2013; 5(10): 3839-53.
     Google Scholar
  38. Roszkowska A, Pawlicka M, Mroczek A, Bałabuszek K, Nieradko-Iwanicka B. Non-Celiac Gluten Sensitivity: A Review. Medicina (Kaunas, Lithuania). 2019; 55(6).
     Google Scholar
  39. Cooper BT, Holmes GK, Ferguson R, Thompson RA, Allan RN, Cooke WT. Gluten-sensitive diarrhea without evidence of celiac disease. Gastroenterology. 1980; 79(5 Pt 1): 801-6.
     Google Scholar
  40. Carroccio A, Brusca I, Mansueto P, Soresi M, D'Alcamo A, Ambrosiano G, et al. Fecal Assays Detect Hypersensitivity to Cow's Milk Protein and Gluten in Adults With Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2011.
     Google Scholar
  41. Nowak-Węgrzyn A, Katz Y, Mehr SS, Koletzko S. Non-IgE-mediated gastrointestinal food allergy. J Allergy Clin Immunol. 2015; 135(5): 1114-24.
     Google Scholar
  42. Agyemang A, Nowak-Wegrzyn A. Food Protein-Induced Enterocolitis Syndrome: a Comprehensive Review. Clin Rev Allergy & Immunol. 2019; 57(2): 261-71.
     Google Scholar
  43. Tan JA, Smith WB. Non-IgE-mediated gastrointestinal food hypersensitivity syndrome in adults. J Allergy Clin Immunol Pract. 2014; 2(3): 355-7.
     Google Scholar
  44. Lied GA. Indication of immune activation in patients with perceived food hypersensitivity. Dig Dis Sci. 2014; 59(2): 259-66.
     Google Scholar
  45. Olivares M, Flor-Duro A, Sanz Y. Manipulation of the gut microbiome in gluten-intolerance. Current opinion in clinical nutrition and metabolic care. 2021; 24(6): 536-42.
     Google Scholar
  46. Beuthin J, Veronesi M, Grosberg B, Evans RW. Gluten-Free Diet and Migraine. Headache. 2020; 60(10): 2526-9.
     Google Scholar
  47. Cabrera-Chávez F, Dezar GV, Islas-Zamorano AP, Espinoza-Alderete JG, Vergara-Jiménez MJ, Magaña-Ordorica D, et al. Prevalence of Self-Reported Gluten Sensitivity and Adherence to a Gluten-Free Diet in Argentinian Adult Population. Nutrients. 2017; 9(1).
     Google Scholar
  48. Halliday WJ, Miller S. Leukocyte adherence inhibition: a simple test for cell-mediated tumour immunity and serum blocking factors. Int J Cancer. 1972; 9(3): 477-83.
     Google Scholar
  49. Bullen AW, Losowsky MS. Comparison of a leucocyte adherence test with the leucocyte migration inhibition test and skin reactivity to PPD. Clin Exp Immunol. 1978; 31(3): 408-13.
     Google Scholar
  50. Kuratsuji T. Studies on leukocyte adherence inhibition test. Part II. Clinical applications of LAI test to detect delayed type hypersensitivity in infants and children. Keio J Med. 1981; 30(2): 65-9.
     Google Scholar
  51. Kuratsuji T. Studies on leukocyte adherence inhibition test. Part I. Studies on mechanisms of leukocyte adherence inhibition. Keio J Med. 1981; 30(2): 53-63.
     Google Scholar
  52. Olivier CE, Lima RPS, Pinto DG, Santos RAPG, Silva GKM, Lorena SLS, et al. In search of a tolerance-induction strategy for cow's milk allergies: significant reduction of beta-lactoglobulin allergenicity via transglutaminase/cysteine polymerization. Clinics. 2012; 67(10): 1171-9.
     Google Scholar
  53. Thomson DMP. Assessment of immune status by the leukocyte adherence inhibition test. New York: Academic Press; 1982; xvii: 380.
     Google Scholar
  54. Halliday WJ. Historical Background and Aspects of the Mechanism of Leukocyte Adherence Inhibition. Cancer Res. 1979; 39(2): 558-63.
     Google Scholar
  55. Appelboom T, Famaey JP, Gortz R, Wybran J. Effect of levamisole on leukocyte adherence inhibition. Agents Actions. 1981; 11(6-7): 604-5.
     Google Scholar
  56. Fink A, Bibi H, Eliraz A, Tabachnik E, Bentwich Z. Leukotrienes (LTC4, LTD4) confer glass non-adherence on leukocytes of asthmatic individuals. Dependency on cyclooxygenase products and calcium ion. Immunol Lett. 1985; 10(6): 319-23.
     Google Scholar
  57. Fink A, Shahin R, Eliraz A, Bibi H, Berkenstadt H, Levin S, et al. Interferon modulates the leukotriene C4-induced non-adherence properties of leukocytes: acquisition of an asthmatic phenotype. Immunol Lett. 1985; 10(3-4): 159-63.
     Google Scholar
  58. Iwabuchi K, Yamashita T. Platelet-derived neutrophil adherence-inhibiting factor in humans. Blood. 1990; 76(11): 2368-73.
     Google Scholar
  59. Kotlar HK, Sanner T. Role of circulating antibodies in the humoral leukocyte adherence inhibition response of lung and breast cancer patients. Cancer Lett. 1980; 11(1): 11-9.
     Google Scholar
  60. Powell AE, Birch RE, Murrell H, Sloss AM. Cell populations in leucocyte adherence inhibition: requirement for T lymphocytes with IgG Fc receptors. Immunology. 1982; 46(4): 689-96.
     Google Scholar
  61. Powell AE, Sloss AM, Smith RN. Leukocyte-Adherence Inhibition: A Specific Assay of Cell-Mediated Immunity Dependent on Lymphokine-Mediated Collaboration between T Lymphocytes. The J Immunol. 1978; 120(6): 1957-66.
     Google Scholar
  62. Olivier CE, Lima RPdS, Pinto DG, Santos RAPGd. The Plasma Preincubation with Papain Before the Assay Suggests that a Gell and Coombs Type II Reaction is Been Demonstrated by the Leukocyte Adherence Inhibition Test. Biomedical Journal of Scientific & Technical Research. 2021; 36(3): 28647 - 55.
     Google Scholar
  63. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013; 310(20): 2191-4.
     Google Scholar
  64. Olivier CE, Argentão DGP, Santos RAPG, Silva MD, Lima RPS, Zollner RL. Skin scrape test: an inexpensive and painless skin test for recognition of immediate hypersensitivity in children and adults. The Open Allergy Journal. 2013; 6: 9-17.
     Google Scholar
  65. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248-54.
     Google Scholar
  66. Olivier CE, Pinto DG, Lima RPS, Silva MDd, Santos RAPG, Teixeira APM, et al. Assessment of Immunoreactivity against Therapeutic Options Employing the Leukocyte Adherence Inhibition Test as a Tool for Precision Medicine. Eur J Clin Med. 2021; 2(3): 40-5.
     Google Scholar
  67. Kim H-Y. Statistical notes for clinical researchers: Nonparametric statistical methods: 1. Nonparametric methods for comparing two groups. Restorative dentistry & endodontics. 2014; 39(3): 235-9.
     Google Scholar
  68. Fay MP, Proschan MA. Wilcoxon-Mann-Whitney or t-test? On assumptions for hypothesis tests and multiple interpretations of decision rules. Stat Surv. 2010; 4: 1-39.
     Google Scholar
  69. Chiang D, Chen X, Jones SM, Wood RA, Sicherer SH, Burks AW, et al. Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector T(H)2 subsets. J Allergy Clin Immunol. 2018; 141(6): 2107-20.
     Google Scholar
  70. Nakajima H, Hachimura S, Nishiwaki S, Katsuki T, Shimojo N, Ametani A, et al. Establishment and characterization of alpha s1-casein-specific T-cell lines from patients allergic to cow's milk: unexpected higher frequency of CD8+ T-cell lines. J Allergy Clin Immunol. 1996; 97(6): 1342-9.
     Google Scholar
  71. Vandamme C, Rytkönen-Nissinen M, Lönnberg T, Randell J, Harvima RJ, Kinnunen T, et al. Single-cell characterization of dog allergen-specific T cells reveals T(H)2 heterogeneity in allergic individuals. J Allergy Clin Immunol. 2021.
     Google Scholar
  72. Würtzen P, Wissenbach M, Ipsen H, Bufe A, Arnved J, van Neerven RJ. Highly heterogeneous Phl p 5-specific T cells from patients with allergic rhinitis differentially recognize recombinant Phl p 5 isoallergens. J Allergy Clin Immunol. 1999; 104(1): 115-22.
     Google Scholar
  73. Bischoff SC, Herrmann A, Manns MP. Prevalence of adverse reactions to food in patients with gastrointestinal disease. Allergy. 1996; 51(11): 811-8.
     Google Scholar
  74. Ortolani C, Bruijnzeel-Koomen C, Bengtsson U, Bindslev-Jensen C, Björkstén B, Høst A, et al. Controversial aspects of adverse reactions to food. European Academy of Allergology and Clinical Immunology (EAACI) Reactions to Food Subcommittee. Allergy. 1999; 54(1): 27-45.
     Google Scholar
  75. Bengtsson U, Nilsson-Balknäs U, Hanson LA, Ahlstedt S. Double blind, placebo controlled food reactions do not correlate to IgE allergy in the diagnosis of staple food related gastrointestinal symptoms. Gut. 1996; 39(1): 130-5.
     Google Scholar
  76. Robinson LB, Arroyo AC, Mehta GD, Rudders SA, Camargo CA. No allergy left behind: The importance of food allergy in longitudinal cohorts. Ann Allergy Asthma Immunol. 2021.
     Google Scholar
  77. Olivier CE. Food Allergy. Journal of Allergy & Therapy. 2013; S3: 4: 1-7.
     Google Scholar
  78. Burrows AG, Ellis AK. Idiopathic anaphylaxis: Diagnosis and management. Allergy Asthma Proc. 2021; 42(6): 481-8.
     Google Scholar
  79. Kerschenlohr K, Decard S, Darsow U, Ollert M, Wollenberg A. Clinical and immunologic reactivity to aeroallergens in "intrinsic" atopic dermatitis patients: J Allergy Clin Immunol. 2003; 111(1): 195-7.
     Google Scholar
  80. Karimkhani C, Silverberg JI, Dellavalle RP. Defining intrinsic vs. extrinsic atopic dermatitis. Dermatol Online J. 2015; 21(6).
     Google Scholar
  81. Tokura Y. Extrinsic and intrinsic types of atopic dermatitis. J Dermatol Sci. 2016; 58(1): 1-7.
     Google Scholar
  82. Olivier CE, Pinto DG, Teixeira APM, Santana JLS, Santos RAPGS, Lima RPS. Immunoreactivity against Dermatophagoides pteronyssinus Assessed by the Leukocyte Adherence Inhibition Test in Patients with Intrinsic Atopic Dermatitis and Correlated “Intrinsic” Non–IgE-mediated Allergic Conditions. Eur J Clin Med. 2021; 2(6): 45-50.
     Google Scholar
  83. Olivier CE, Pinto DG, Teixeira APM, Santana JLS, Santos RAPGS, Lima RPS. Contribution of the Leukocyte Adherence Inhibition Test to the Evaluation of Cellular Immunoreactivity against Latex Extracts for Non—IgE-Mediated Latex-Fruit-Pollen Syndrome in Allergic Candidates to Exclusion Diets and Allergic Desensitization. Eur J Clin Med. 2022; 3(1): 11-7.
     Google Scholar
  84. Commins SP, Satinover SM, Hosen J, Mozena J, Borish L, Lewis BD, et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol. 2009; 123(2): 426-33.
     Google Scholar
  85. Glaros V, Rauschmeier R, Artemov AV, Reinhardt A, Ols S, Emmanouilidi A, et al. Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response. Immunity. 2021; 54(9): 2005-23.e10.
     Google Scholar
  86. Dunn IS, Halliday WJ. Interactions between T and B lymphocytes and macrophages in the production of leukocyte adherence inhibition factor. Cellular Immunology. 1980; 52(1): 48-61.
     Google Scholar


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