Efficacy of Oral Antigen Specific Immunotherapy on Desensitization of Some Autoimmune Diseases Associated with Milk Allergy


There are several reports on the prevalence and importance of milk allergens in the induction of allergic diseases, whereas its role in the induction of autoimmune disease was rarely studied. So, the present work aimed to study the diagnosis and the efficacy of oral antigen specific immunotherapy (OAIT) on two groups of autoimmune disease patients namely, rheumatic arthritis (RA), group II, and systemic lupus erythematosus (SLE), group III, who has allergens for milk as an effective treatment option. From the assessment of the data obtained and the clinical outcome of RA and SLE patients after food elimination strategy and milk immunotherapy, it was evident that there were significant reductions (P < 0.001) in the levels of total IgE, specific IgE, Rheumatic factor (R.F), C-reactive protein (C.R.P), Anti-nuclear antibodies (ANA) and anti-double stranded DNA antibodies (Anti-ds DNA) compared to pretreated levels. Moreover, the immunotherapy induced “blocking antibodies” by remarkable highly significant increasing in IgG, phagocytic inhibition test (PIT %), Complement component 3(C3), and Complement component 4 (C4) levels. More improvement was noticed in the SLE as a result of the immunotherapy. Conclusion: milk desensitization is a gained interest and a safe valuable effective treatment of autoimmune conditions in Egypt.

Share and Cite:

A. Atef, M. Attia and O. Abdel Aal, "Efficacy of Oral Antigen Specific Immunotherapy on Desensitization of Some Autoimmune Diseases Associated with Milk Allergy," Food and Nutrition Sciences, Vol. 4 No. 8, 2013, pp. 799-806. doi: 10.4236/fns.2013.48104.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] H. Y. Lam, E. van Hoffen, A. Michelsen, K. Guikers, C. H. van der Tas, C. A. Bruijnzeel-Koomen and A. C. Knulst, “Cow’s Milk Allergy in Adults Is Rare but severe: Both Casein and Whey Proteins Are Involved,” Clinical and Experimental Allergy, Vol. 36, No. 38, 2008, pp. 995-1002.
[2] S. H. Sicherer, “Food Allergy,” The Mount Sinai Journal of Medicine, Vol. 78, No. 5, 2011, pp. 683-696. doi:10.1002/msj.20292
[3] J. M. Wal, “Bovine Milk Allergenicity,” Annals Allergy Asthma & Immunology, Vol. 93, No. 5, 2004, pp. S2-S11. doi:10.1016/S1081-1206(10)61726-7
[4] P. Restani, C. Ballabio and C. Lorenzo, “Molecular As pects of Milk Allergens and Their Role in Clinical Events,” Analytical and Bioanalytical Chemistry, Vol. 395, No. 1, 2009, pp. 47-56.
[5] G. A. Lied, K. Lillestol, J. Valeur and A. Berstad, “Intestinal B Cell-Activating Factor: An Indicator of Non IgE-Mediated Hypersensitivity Reactions to Food?” Ali mentary Pharmacology & Therapeutics, Vol. 32, No. 2, 2010, pp. 66-73. doi:10.1111/j.1365-2036.2010.04314.x
[6] B. Schouten, B. C. A. M. Van Esch and A. O. J. Van Thuijl, “Contribution of IgE and Immunoglobulin Free Light Chain in the Allergic Reaction to Cow’s Milk Pro teins,” Journal Allergy Clinical Immunology, Vol. 125, No. 2, 2010, pp. 1308-1314. doi:10.1016/j.jaci.2010.02.039
[7] S. H. Sicherer, “Food Allergy: When and How to Perform Oral Food Challenges,” Pediatric Allergy Immunology, Vol. 10, No. 3, 1999, pp. 226-234. doi:10.1034/j.1399-3038.1999.00040.x
[8] I. M. Roitt, J. Brostoff and D. K. Male, “Immunology,” 4th Edition, Gower Medical Publishing Ltd., London, 1996, pp. 150-640.
[9] N. Wegner, K. Lundberg and A. Kinloch, “Autoimmunity to Specific Citrullinated Proteins Gives the First Clues to the Etiology of Rheumatoid Arthritis,” Immunological Reviews, Vol. 233, No. 3, 2010, pp. 34-54. doi:10.1111/j.0105-2896.2009.00850.x
[10] S. Karatay, T. Erdem and K. Yildirim, “The Effect of Individualized Diet Challenges Consisting of Allergenic Foods on TNF-Alpha and IL-1Beta Levels in Patients with Rheumatoid Arthritis,” Rheumatology, Vol. 43, No. 11, 2004, pp. 1429-1433.
[11] A. Martorell, A. M. Plaza, J. Boné, S. Nevot, M. C. Gar-cía Ara, L. Echeverria, E. Alonso, J. Garde, B. Vila, M. Alvaro, E. Tauler, V. Hernando and M. Fernández, “Cow’s Milk Protein Allergy. A Multi-Centre Study: Cli nical and Epidemiological Aspects,” Allergology and Im munopathology, Vol. 34, No. 2, 2006, pp. 46-53.
[12] E. Mortensen, K. Fenton and O. Rekvig, “Lupus Nephri tis: The Central Role of Nucleosomes Revealed,” Ameri can Journal Pathology, Vol. 172, No. 2, 2008, pp. 275-283. doi:10.2353/ajpath.2008.070563
[13] R. Asero, G. Mistrello and R. Ariano, “Is Oral Immuno therapy the Cure for Food Allergies?” Current Opinion in Allergy and Clinical Immunology, Vol. 10, No. 2, 2010, pp. 214-219.
[14] A. J. Frew, “Allergen Immunotherapy,” Journal Allergy Clinical Immunology, Vol. 125, No. 2, 2010, pp. 306-313. doi:10.1016/j.jaci.2009.10.064
[15] J. Antunes, L. Borrego, A. Romeira and P. Pinto, “Skin Prick Tests and Allergy Diagnosis,” Allergologia et Im munopathologia, Vol. 37, No. 3, 2009, pp. 155-164. doi:10.1016/S0301-0546(09)71728-8
[16] A. S. El Shami and O. Alaba, “Liquid-Phase in Vitro Allergen-Specific IgE Assay with in Situ Immobiliza tion,” Advanced Bioscience, Vol. 74, No. 3, 1989, pp. 191-201.
[17] C. Pecquet, “IgE-Mediated Allergy to Latex 80 Patients,” The 15th European Congress of Allergology and Clinical Immunology, Paris, 12 May 1992, pp. 1805-1812.
[18] T. M. Li, T. Chuang, S. Tse, D. Hovanec-Burns, A. S. El Shami, “Development and Validation of a Third Genera tion Allergen-Specific IgE Assay on the Continuous Random Access IMMULITE 2000 Analyzer,” Annals of Clinical and Laboratory Science, Vol. 34, No. 1, 2004, pp. 67-74.
[19] R. Verbruggen, “Subtilopeptidase A Isoenzyme System. Interaction with Serum Components and Its Importance for Quantitative Immnoelectrophoresis,” Biochemistrical Journal, Vol. 151, No. 1, 1975, pp. 149-155.
[20] K. L. Bandilla and F. C. Mc Duffie, “Latex Agglutination Slide Test for Quantitative and Semi Quantitative Deter mination of Rheumatoid Factors in Non-Diluted (ND) Serum,” Journal Arithritis Rheumatism, Vol. 2, No. 1, 2009, pp. 12-74.
[21] S. P. Ballou and I. Kushner, “C-Reactive Protein and the Acute Phase Response,” Advances in Internal Medicine, Vol. 37, No. 2, 1992, pp. 313-336.
[22] D. E. Soliman and M. Yousef, “Specific Phagocytic Inhi bition Test (A New Assay) in Diagnosis of Foods, Aspi rin and Inhalants Allergy,” Azhar Collaege Journal Azhar Medicine Faculty (Girls), Vol. 28, No. 3, 2007, pp. 559-575.
[23] K. Egerer, D. Roggenbuck and R. Hiemann, “Automated Evaluation of Autoantibodies on Human Epithelial-2 Cells as an Approach to Standardize Cell-Based Immunofluo rescence Tests,” Arthritis Research & Therapy, Vol. 12, No. 40, 2010, p. R40.
[24] H. Scott, S. Sampson and A. Hugh, “Food Allergy [Mis cellaneous],” Journal of Allergy & Clinical Immunology, Vol. 125, No. 2, 2010, pp. 116-125.
[25] R. Kumar, B. P. Singh and P. Srivastava, “Relevance of Serum IgE Estimation in Allergic Bronchial Asthma with Special Reference to Food Allergy,” Journal of Allergy and Immunology, Vol. 24, No. 2, 2006, pp. 191-199.
[26] I. Sekigawa, Y. Tokano, T. Yoshiike, N. Iida, H. Hashi moto and H. Ogawa, “Relationship between Serum IgE and Autoantibody Levels in SLE Patients,” Clinical Ex perimental Rheumatology, Vol. 21, No. 2, 2003, p. 683.
[27] K. R. Krishnan, E. L. Peterson and G. Wegienka, “Pattern of Allergen-Specific IgE Sensitization Relative to Total Serum Ig Concentration in Young Adults,” Annals of Allergy, Asthma & Immunology, Vol. 105, No. 5, 2010, pp. 401-403. doi:10.1016/j.anai.2010.09.014
[28] M. B. Pepysand and G. M. Hirschfield, “C-Reactive Protein: A Critical Update,” Journal of Clinical Investigations, Vol. 111, No. 112, 2003, pp. 1805-1812.
[29] D. L. Mallery, W. A. McEwan and S. R. Bidgood, “An tibodies Mediate Intracellular Immunity through Tripar tite Motif-Containing 21(TRIM21),” Proceedings of the National Academy of Sciences of the USA, Vol. 107, No. 46, 2010, pp. 19985-19990. doi:10.1073/pnas.1014074107
[30] J. M. Skripak, E.C. Matsui, K. Mudd and R. A. Wood, “The Natural History of IgE-Mediated Cow’s Milk Al lergy,” Journal of Allergy and Clinical Immunollogy, Vol. 120, No. 2, 2007, pp. 1172-1177.
[31] S. Black, I. Kushner and D. Samols, “C-Reactive Protein,” Journal of Biological Chemistry, Vol. 279, No. 3, 2004, pp. 48487-48490. doi:10.1074/jbc.R400025200
[32] K. Bidad, M. H. Nicknam and R. Farid, “A Review of Allergy and Allergen Specific Immunotherapy,” Iranian Journal of Allergy, Asthma and Immunology, Vol. 10, No. 1, 2011, pp. 1-9.
[33] C. Garcia-Ara, T. Byano-Martinez and J. M. Diaz-Pena, “Specific IgE Levels in the Diagnosis of Immediate Hy persensitivity to Cow’s Milk Protein in the Infants,” Jour nal of Allergy Clinical Immunology, Vol. 107, No. 1, 2001, pp. 185-190. doi:10.1067/mai.2001.111592
[34] E. Hidvegi, E. Cserhati, E. Kereki and E. Savilahti, “Serum Immunoglobulin E, IgA, and IgG Antibodies to Different Cow’s Milk Proteins in Children with Cow’s Milk Allergy: Association with Prognosis and Clinical Manifestations,” Pediatric Allergy Immunology, Vol. 13, No. 4, 2002, pp. 255-261. doi:10.1034/j.1399-3038.2002.01045.x
[35] A. Douglass Jo and E. R. O’Hehir, “Diagnosis, Treatment and Prevention of Allergic Disease: The Basics,” Medical Journal Australia, Vol. 185, No. 4, 2006, pp. 228-233.
[36] A. M. Atta, C. P. Sousa, E. M. Carvalho and M. L. Sousa Atta, “Immunoglobulin E and Systemic Lupus Erythe matosus,” Brazil Journal of Medical Biology Research, Vol. 37, No. 10, 2004, pp. 1497-1501.
[37] S. Flicker and R. Valenta, “Renaissance of the Blocking Antibody Concept in Type I Allergy,” International Ar chives of Allergy and Immunology, Vol. 132, No. 1, 2003, pp. 13-24. doi:10.1159/000073260
[38] S. Flicker, E. Gadermaier, C. Madritsch and R. Valenta, “Passive Immunization with Allergen-Specific Antibod ies,” Current Topics in Microbiology and Immunology, Vol. 3535, No. 2, 2011, pp. 141-159. doi:10.1007/82_2011_143
[39] I. A. Emanuel, M. J. Parker and O. Traub, “Under Treat ment of Allergy: Exploring the Utility of Sublingual Im munotherapy,” Otolaryngology-Head Neck Surgery, Vol. 140, No. 2, 2009, pp. 615-621. doi:10.1016/j.otohns.2009.01.023
[40] K. M. Ho and J. Lipman, “An Update on C-Reactive Pro tein for Intensives,” Anaesthesia and Intensive Care Journal, Vol. 37, No. 2, 2009, pp. 234-241.
[41] C. G. Parks, R. E. Biagini, G. S. Cooper, “Total Serum IgE Levels in Systemic Lupus Erythematosus and Asso ciations with Childhood Onset Allergies,” Lupus Journal, Vol. 19, No. 5, 2010, pp. 1614-1622. doi:10.1177/0961203310379870
[42] J. Smolen, “Rheumatoid Arthritis,” In: R. N. Maini and W. J. van Venrooij, Eds., Manual of Biological Markers of Disease, Kluwer Academic Publishers, Amsterdam, 1996, pp. 1-18. doi:10.1007/978-94-011-1670-1_37
[43] R. C. Williams, M. E. Harmon, R. Burlingame and T. W. Du Clos, “Studies of Serum C-Reactive Protein in Sys temic Lupus Erythematosus,” Journal Rheumatology, Vol. 32, No. 3, 2005, pp. 454-461.
[44] J. M. Gill, A. M. Quisel, P. V. Rocca and D. T. Walters, “Diagnosis of Systemic Lupus Erythematosus,” American Family Physician, Vol. 68, No. 5, 2003, p. 2179.
[45] C. K. Ting and K. A Hsieh, “A Long-Term Immunologi cal Study of Childhood Onset Systemic Lupus Erythe matosus,” Annuals of the Rheumatic Diseases, Vol. 51, No. 1, 1992, pp. 45-51.
[46] I. Gilboe and G. Husby, “Application of the 1982 Revised Criteria for the Classification of Systemic Lupus Erythe matosus on a Cohort of 346 Norwegian Patients with Connective Tissue Disease,” Scandinavian Journal of Rheumatology, Vol. 28, No. 2, 1999, pp. 81-87. doi:10.1080/030097499442531
[47] J. M. Esdaile, L. Joseph and M. Abrahamowicz, “Routine Immunologic Tests in Systemic Lupus Erythematosus: Is There a Need for More Studies?” The Journal of Rheu matology, Vol. 23, No. 11, 1996, pp. 1891-1896.
[48] N. Hussain, G. Jaffery and S. Hasnain, “Serum Complement C3 and C4 Levels in Relation to Diagnosis of Lupus Nephritis,” Tropical Journal of Pharmaceutical Research, Vol. 7, No. 4, 2008, pp. 1117-1121.
[49] C. C. Liu, S. Manzi and A. H. Kao, “Reticulocytes Bearing C4d as Biomarkers of Disease Activity for Systemic lupus Erythematosus,” Arthritis & Rheumatism, Vol. 52, No. 10, 2005, pp. 3087-3099. doi:10.1002/art.21305

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.