Purpose
Atopy patch tests (APTs) allow the detection of delayed allergies at the skin level. The localization of β-lactoglobulin delivered into the skin by an innovative ready-to-use APT (E-patch®) was investigated and the efficacy and safety of this device were assessed.
Methods
The E-patch® containing β-lactoglobulin was placed for 24 h in contact with hairless rat skin mounted in a Franz diffusion cell. Transdermal passage was monitored by measurement of β-lactoglobulin A-[methyl-14C] or by two-site enzyme immunoassay. An iterative skin stripping allowed measurement of the β-lactoglobulin penetrating the first external skin layers.
Results
After 24 h, 92% of β-lactoglobulin remained on the skin. The iterative skin strippings showed a 135-fold higher concentration of β-lactoglobulin in the stratum corneum than that found in the epidermis–dermis. Analysis of the solution in the receiver compartment by radioactivity assays or immunoassays indicates that intact protein did not cross the skin.
Conclusions
The E-patch® system allows native β-lactoglobulin to concentrate in the stratum corneum, in the vicinity of immunological cells, but does not lead to its systemic delivery. Therefore, it is suggested that this delivery system creates ideal conditions for promoting a positive topical response with reduced risk of systemic anaphylactic reactions caused by the native form of the β-lactoglobulin A.
Similar content being viewed by others
References
T. Vanto K. Juntunen-Backman K. Kalimo T. Klemola A. Koivikko P. Koskinen P. Syvanen E. Valovirta E. Varjonen (1999) ArticleTitleThe patch test, skin prick test, and serum milk-specific IgE as diagnostic tools in cow’s milk allergy in infants Allergy 54 837–842 Occurrence Handle10.1034/j.1398-9995.1999.00134.x Occurrence Handle10485387
J. M. Wal (2002) ArticleTitleCow’s milk proteins/allergens Ann. Allergy, Asthma, & Immun. 89 3–10
S. A. Bock H. A. Sampson F. M. Atkins R. S. Zeiger S. Lehrer M. Sachs R. K. Bush D. D. Metcalfe (1988) ArticleTitleDouble-blind, placebo-controlled food challenge (DBPCFC) as an office procedure: a manual J. Allergy Clin. Immunol. 82 986–997 Occurrence Handle10.1016/0091-6749(88)91021-4 Occurrence Handle3060514
L. Rasanen M. Lehto T. Reunala (1992) ArticleTitleDiagnostic value of skin and laboratory tests in cow’s milk allergy/intolerance Clin. Exp. Allergy 22 385–390 Occurrence Handle1375126
E. Isolauri K. Turjanmaa (1996) ArticleTitleCombined skin prick and patch testing enhances identification of food allergy in infants with atopic dermatitis J. Allergy Clin. Immunol. 97 9–15 Occurrence Handle8568142
C. C. Roehr S. Reibel M. Ziegert C. Sommerfeld U. Wahn B. Niggemann (2001) ArticleTitleAtopy patch tests, together with determination of specific IgE levels, reduce the need for oral food challenges in children with atopic dermatitis J. Allergy Clin. Immunol. 107 548–553 Occurrence Handle10.1067/mai.2001.112849 Occurrence Handle11240959
C. Dupont D. Boissieu Particlede (2002) ArticleTitleMilk and atopy Rev. Fr. Allergol. Immunol. Clin. 42 574–582
D. Jaffuel P. Demoly J. Bousquet (2001) ArticleTitleFood allergies Rev. Fr. Allergol. Immunol. Clin. 41 169–186 Occurrence Handle10.1016/S0335-7457(01)00010-7
D. Schmitt (1994) ArticleTitleCutaneous immune system C. R. Seances Soc. Biol. Fil. 188 207–221 Occurrence Handle7834504
I. Kimber M. Cumberbatch (1992) ArticleTitleDendritic cells and cutaneous immune responses to chemical allergens Toxicol. Appl. Pharmacol. 117 137–146 Occurrence Handle10.1016/0041-008X(92)90230-P Occurrence Handle1471146
N. Novak J. Haberstok E. Geiger T. Bieber (1999) ArticleTitleDendritic cells in allergy Allergy 54 792–803 Occurrence Handle10.1034/j.1398-9995.1999.00101.x Occurrence Handle10485382
B. Niggemann S. Reibel U. Wahn (2000) ArticleTitleThe atopy patch test (APT)–a useful tool for the diagnosis of food allergy in children with atopic dermatitis Allergy 55 281–285 Occurrence Handle10.1034/j.1398-9995.2000.00464.x Occurrence Handle10753020
D. Boissieu ParticleDe J. C. Waguet C. Dupont (2003) ArticleTitleThe atopy patch tests for detection of cow’s milk allergy with digestive symptoms J. Pediatr. 142 203–205 Occurrence Handle10.1067/mpd.2003.92 Occurrence Handle12584547
J. J. Berti J. J. Lipsky (1995) ArticleTitleTranscutaneous drug delivery: a practical review Mayo Clin. Proc. 70 581–586 Occurrence Handle7776720
O. M. Kekki K. Turjanmaa E. Isolauri (1997) ArticleTitleDifferences in skin-prick and patch-test reactivity are related to the heterogeneity of atopic eczema in infants Allergy 52 755–759 Occurrence Handle9265992
H. Majamaa P. Moisio K. Holm H. Kautiainen K. Turjanmaa (1999) ArticleTitleCow’s milk allergy: diagnostic accuracy of skin prick and patch tests and specific IgE Allergy 54 346–351 Occurrence Handle10.1034/j.1398-9995.1999.00834.x Occurrence Handle10371093
L. Stromberg (2002) ArticleTitleDiagnostic accuracy of the atopy patch test and the skin-prick test for the diagnosis of food allergy in young children with atopic eczema/dermatitis syndrome Acta Paediatr. 91 1044–1049 Occurrence Handle10.1080/080352502760311520 Occurrence Handle12434888
E. Berardesca G. P. Vignoli D. Fideli H. Maibach (1992) ArticleTitleEffect of occlusive dressings on the stratum corneum water holding capacity Am. J. Med. Sci. 304 25–28 Occurrence Handle1642249
T. Agner J. Serup (1993) ArticleTitleTime course of occlusive effects on skin evaluated by measurement of transepidermal water loss (TEWL). Including patch tests with sodium lauryl sulphate and water Contact Dermatitis 28 6–9 Occurrence Handle8428461
T. M. Keahey K. B. Yancey T. J. Lawley (1987) ArticleTitleImmediate hypersensitivity J. Am. Acad. Dermatol. 17 826–837 Occurrence Handle3316320
J. M. Wal (2001) ArticleTitleStructure and function of milk allergens Allergy 56 IssueIDSuppl 67 35–38 Occurrence Handle10.1111/j.1398-9995.2001.00911.x
T. N. Koritz S. Suzuki R. R. Coombs (1987) ArticleTitleAntigenic stimulation with proteins of cow’s milk via the oral route in guinea pigs and rats. 1. Measurement of antigenically intact beta-lactoglobulin and casein in the gastrointestinal contents of duodenum, jejunum and ileum Int. Arch. Allergy Appl. Immunol. 82 72–75 Occurrence Handle3804456
L. Negroni H. Bernard G. Clement J. M. Chatel P. Brune Y. Frobert J. M. Wal J. Grassi (1998) ArticleTitleTwo-site enzyme immunometric assays for determination of native and denatured beta-lactoglobulin J. Immunol. Methods 220 25–37 Occurrence Handle10.1016/S0022-1759(98)00150-1 Occurrence Handle9839923
D. Dottavio-Martin J. M. Ravel (1978) ArticleTitleRadiolabeling of proteins by reductive alkylation with [14C]formaldehyde and sodium cyanoborohydride Anal. Biochem. 87 562–565 Occurrence Handle10.1016/0003-2697(78)90706-6 Occurrence Handle567446
W. A. Ritschel (1987) ArticleTitleIn vivo animal models for bioavailability assessment STP Pharma 3 125–141
C. D. Partidos A. S. Beignon F. Brown E. Kramer J. P. Bri S. Muller (2002) ArticleTitleApplying peptide antigens onto bare skin: induction of humoral and cellular immune responses and potential for vaccination J. Control. Release 85 27–34 Occurrence Handle10.1016/S0168-3659(02)00268-7 Occurrence Handle12480308
G. M. Glenn T. Scharton-Kersten R. Vassell C. P. Mallett T. L. Hale C. R. Alving (1998) ArticleTitleTranscutaneous immunization with cholera toxin protects mice against lethal mucosal toxin challenge J. Immunol. 161 3211–3214 Occurrence Handle9759833
S. A. Hammond D. Walwender C. R. Alving G. M. Glenn (2001) ArticleTitleTranscutaneous immunization: T cell responses and boosting of existing immunity Vaccine 19 2701–2707 Occurrence Handle10.1016/S0264-410X(00)00506-5 Occurrence Handle11257412
J. M. Spergel E. Mizoguchi J. P. Brewer T. R. Martin A. K. Bhan R. S. Geha (1998) ArticleTitleEpicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice J. Clin. Invest. 101 1614–1622 Occurrence Handle9541491
K. Egbaria C. Ramachandran D. Kittayanond N. Weiner (1990) ArticleTitleTopical delivery of liposomally encapsulated interferon evaluated by in vitro diffusion studies Antimicrob. Agents Chemother. 34 107–110 Occurrence Handle1691613
B. Niggemann (2002) ArticleTitleAtopy Patch Test (APT)—its role in diagnosis of food allergy in atopic dermatitis Indian J. Pediatr. 69 57–59 Occurrence Handle11876122
K. Perackis S. Celik-Bilgili U. Staden A. Mehl B. Niggemann (2003) ArticleTitleInfluence of age on the outcome of the atopy patch test with food in children with atopic dermatitis J. Allergy Clin. Immunol. 112 625–627 Occurrence Handle10.1016/S0091-6749(03)01627-0 Occurrence Handle13679826
F. Berard J. P. Marty J. F. Nicolas (2003) ArticleTitleAllergen penetration through the skin Eur. J. Dermatol. 13 324–330 Occurrence Handle12948910
N. Sekkat Y. N. Kalia R. H. Guy (2002) ArticleTitleBiophysical study of porcine ear skin in vitro and its comparison to human skin in vivo J. Pharm. Sci. 91 2376–2381 Occurrence Handle10.1002/jps.10220 Occurrence Handle12379922
N. Sekkat Y. N. Kalia R. H. Guy (2004) ArticleTitlePorcine ear skin as a model for the assessment of transdermal drug delivery to premature neonates Pharm. Res. 21 1390–1397 Occurrence Handle10.1023/B:PHAM.0000036912.94452.d0 Occurrence Handle15359573
W. J. Fasano G. L. Kennedy B. Szostek D. G. Farrar R. J. Ward L. Haroun P. M. Hinderliter (2005) ArticleTitlePenetration of ammonium perfluorooctanoate through rat and human skin in vitro Drug Chem. Toxicol. 28 79–90 Occurrence Handle15720037
Acknowledgments
This work was supported by the CNRS, UPS, INRA-CEA, and by DBV Technologies (Boulogne Billancourt, France). The authors would like to thank Dr. Michel Renoir (UMR CNRS 8612) for help with electrophoretic analysis of β-lactoglobulin purity and Dr. Herve Bernard (INRA) for immunodosage. ANRT supported D. Soury (CIFRE).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Soury, D., Barratt, G., Ah-Leung, S. et al. Skin Localization of Cow’s Milk Proteins Delivered by a New Ready-to-Use Atopy Patch Test. Pharm Res 22, 1530–1536 (2005). https://doi.org/10.1007/s11095-005-5881-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-005-5881-4