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Archives of Dermatological Research
Published in: Archives of Dermatological Research 3/2019

Open Access 01-04-2019 | Atopic Dermatitis | Review

Atopic dermatitis and autoimmunity: the occurrence of autoantibodies and their association with disease severity

Authors: James Holmes, Lucy C. Fairclough, Ian Todd

Published in: Archives of Dermatological Research | Issue 3/2019

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Abstract

Atopic dermatitis (AD) is a widespread condition that appears to be increasing in prevalence and severity worldwide, yet the underlying mechanisms are not well understood. Recent research has identified various similarities between AD and autoimmune conditions, as well as indicating that there may be an association between AD and autoimmunity. This systematic review evaluates the association between AD and autoimmunity, as well as between severity of disease in AD and autoimmunity, with an emphasis on the associations with autoantibodies. MEDLINE (1946 to December 2017) and Embase (1974 to December 2017) databases were searched. Further relevant articles were retrieved from reference lists. Only studies measuring direct indicators of autoimmunity, in humans, were included. Qualitative analysis was carried out for all studies. In addition, quantitative analysis was used to evaluate prevalence of IgE autoantibodies and anti-nuclear antibodies (ANAs) in AD patients and control subjects. The Mantel–Haenszel method was used with a random-effects model. 28 studies assessed the occurrence of autoantibodies in AD patients and 16 studies were used to evaluate association between disease severity and autoantibodies. Pooled analysis from 14 studies, involving 986 AD patients and 441 control subjects, showed that IgE autoantibodies were significantly more prevalent in patients with AD (P < 0.00001) than control subjects. Similar analysis was carried out for ANAs, with eight studies that involved 1045 AD patients and 1273 control subjects. ANAs were significantly more prevalent in patients with AD (P = 0.003). This quantitative analysis supported an association between AD and IgE autoantibodies, as well as between AD and ANAs. There was insufficient data to make similar conclusions for other indicators of autoimmunity. The weight of evidence also suggests an association between IgE autoantibodies and disease severity. There was insufficient evidence to make this link for other indicators of autoimmunity.
Literature
1.
Wise F, S M (1933) The 1933 year book of dermatology and syphilology. Year Book Publishers. Inc., Chicago
2.
3.
Williams H, Stewart A, von Mutius E, Cookson W, Anderson HR,, Three Study G (2008) International study of A, allergies in childhood phase O. Is eczema really on the increase worldwide? J Allergy Clin Immunol 121:947–954PubMedCrossRef
4.
Odhiambo JA, Williams HC, Clayton TO, Robertson CF, Asher MI, Group IPTS (2009) Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol 124:1251–1258PubMedCrossRef
5.
6.
7.
Flohr C, Johansson SG, Wahlgren CF, Williams H (2004) How atopic is atopic dermatitis? J Allergy Clin Immunol 114:150–158PubMedCrossRef
8.
Abeck D, Mempel M (1998) Staphylococcus aureus colonization in atopic dermatitis and its therapeutic implications. Br J Dermatol 139(Suppl 53):13–16PubMedCrossRef
9.
10.
Andersen YM, Egeberg A, Gislason GH, Skov L, Thyssen JP (2017) Autoimmune diseases in adults with atopic dermatitis. J Am Acad Dermatol 76:274–280PubMedCrossRef
11.
12.
13.
Beck LA, Thaci D, Hamilton JD, Graham NM, Bieber T, Rocklin R, Ming JE, Ren H, Kao R, Simpson E, Ardeleanu M, Weinstein SP, Pirozzi G, Guttman-Yassky E, Suarez-Farinas M, Hager MD, Stahl N, Yancopoulos GD, Radin AR (2014) Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 371:130–139PubMedCrossRef
14.
Tang TS, Bieber T, Williams HC (2012) Does “autoreactivity” play a role in atopic dermatitis? J Allergy Clin Immunol 129:1209–1215PubMedCrossRef
15.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535PubMedPubMedCentralCrossRef
16.
Du Toit G, Prescott R, Lawrence P, Johar A, Brown G, Weinberg EG, Motala C, Potter PC (2006) Autoantibodies to the high-affinity IgE receptor in children with chronic urticaria. Ann Allergy Asthma Immunol 96:341–344PubMedCrossRef
17.
Aichberger KJ, Mittermann I, Reininger R, Seiberler S, Swoboda I, Spitzauer S, Kopp T, Stingl G, Sperr WR, Valent P, Repa A, Bohle B, Kraft D, Valenta R (2005) Hom s 4, an IgE-reactive autoantigen belonging to a new subfamily of calcium-binding proteins, can induce Th cell type 1-mediated autoreactivity. J Immunol 175:1286–1294PubMedCrossRef
18.
Altrichter S, Kriehuber E, Moser J, Valenta R, Kopp T, Stingl G (2008) Serum IgE autoantibodies target keratinocytes in patients with atopic dermatitis. J Invest Dermatol 128:2232–2239PubMedCrossRef
19.
Guarneri F, Costa C, Foti C, Hansel K, Guarneri C, Guarneri B, Lisi P, Stingeni L (2015) Frequency of autoallergy to manganese superoxide dismutase in patients with atopic dermatitis: experience of three Italian dermatology centres. Br J Dermatol 173:559–562PubMedCrossRef
20.
Hiragun M, Hiragun T, Ishii K, Suzuki H, Tanaka A, Yanase Y, Mihara S, Haruta Y, Kohno N, Hide M (2014) Elevated serum IgE against MGL_1304 in patients with atopic dermatitis and cholinergic urticaria. Allergol Int 63:83–93PubMedCrossRef
21.
Ilves T, Virolainen A, Harvima IT (2016) Immediate wheal reactivity to autologous sweat in atopic dermatitis is associated with clinical severity, serum total and specific IgE and sweat tryptase activity. Int Arch Allergy Immunol 170:84–91PubMedCrossRef
22.
Kawamoto N, Yamada A, Ohkouchi S, Maeda T, Tanaka S, Hashimoto T, Saijo Y, Saijo S, Nukiwa T, Shichijo S, Aizawa H, Itoh K (2003) IgG reactive to CTL-directed epitopes of self-antigens is either lacking or unbalanced in atopic dermatitis patients. Tissue Antigens 61:352–361PubMedCrossRef
23.
Kortekangas-Savolainen O, Peltonen S, Pummi K, Kalimo K, Savolainen J (2004) IgE-binding components of cultured human keratinocytes in atopic eczema/dermatitis syndrome and their crossreactivity with Malassezia furfur. Allergy 59:168–173PubMedCrossRef
24.
Mittermann I, Reininger R, Zimmermann M, Gangl K, Reisinger J, Aichberger KJ, Greisenegger EK, Niederberger V, Seipelt J, Bohle B, Kopp T, Akdis CA, Spitzauer S, Valent P, Valenta R (2008) The IgE-reactive autoantigen Hom s 2 induces damage of respiratory epithelial cells and keratinocytes via induction of IFN-gamma. J Invest Dermatol 128:1451–1459PubMedCrossRef
25.
Mittermann I, Wikberg G, Johansson C, Lupinek C, Lundeberg L, Crameri R, Valenta R, Scheynius A (2016) IgE sensitization profiles differ between adult patients with severe and moderate atopic dermatitis. PLoS One 11:e0156077PubMedPubMedCentralCrossRef
26.
Mothes N, Niggemann B, Jenneck C, Hagemann T, Weidinger S, Bieber T, Valenta R, Novak N (2005) The cradle of IgE autoreactivity in atopic eczema lies in early infancy. J Allergy Clin Immunol 116:706–709PubMedCrossRef
27.
Natter S, Seiberler S, Hufnagl P, Binder BR, Hirschl AM, Ring J, Abeck D, Schmidt T, Valent P, Valenta R (1998) Isolation of cDNA clones coding for IgE autoantigens with serum IgE from atopic dermatitis patients. FASEB J 12:1559–1569PubMedCrossRef
28.
Schmid-Grendelmeier P, Fluckiger S, Disch R, Trautmann A, Wuthrich B, Blaser K, Scheynius A, Crameri R (2005) IgE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis. J Allergy Clin Immunol 115:1068–1075PubMedCrossRef
29.
Valenta R, Maurer D, Steiner R, Seiberler S, Sperr WR, Valent P, Spitzauer S, Kapiotis S, Smolen J, Stingl G (1996) Immunoglobulin E response to human proteins in atopic patients. J Invest Dermatol 107:203–208PubMedCrossRef
30.
Zeller S, Rhyner C, Meyer N, Schmid-Grendelmeier P, Akdis CA, Crameri R (2009) Exploring the repertoire of IgE-binding self-antigens associated with atopic eczema. J Allergy Clin Immunol 124:278–285PubMedCrossRef
31.
Bergman R, Ramon M, Wildbaum G, Avitan-Hersh E, Mayer E, Shemer A, Karin N (2009) Psoriasis patients generate increased serum levels of autoantibodies to tumor necrosis factor-alpha and interferon-alpha. J Dermatol Sci 56:163–167PubMedCrossRef
32.
Neuber K, Mahnss B, Hubner C, Gergely H, Weichenthal M (2006) Autoantibodies against CD28 are associated with atopic diseases. Clin Exp Immunol 146:262–269PubMedPubMedCentralCrossRef
33.
Ochs RL, Muro Y, Si Y, Ge H, Chan EK, Tan EM (2000) Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. J Allergy Clin Immunol 105:1211–1220PubMedCrossRef
34.
Szakos E, Lakos G, Aleksza M, Hunyadi J, Farkas M, Solyom E, Sipka S (2004) Relationship between skin bacterial colonization and the occurrence of allergen-specific and non-allergen-specific antibodies in sera of children with atopic eczema/dermatitis syndrome. Acta Derm Venereol 84:32–36PubMedCrossRef
35.
Ambrozic A, Avicin T, Ichikawa K, Kveder T, Matsuura E, Hojnik M, Atsumi T, Rozman B, Koike T (2002) Anti-beta(2)-glycoprotein I antibodies in children with atopic dermatitis. Int Immunol 14:823–830PubMedCrossRef
36.
El-Rachkidy RG, Young HS, Griffiths CE, Camp RD (2008) Humoral autoimmune responses to the squamous cell carcinoma antigen protein family in psoriasis. J Invest Dermatol 128:2219–2224PubMedCrossRef
37.
Ress K, Teesalu K, Annus T, Putnik U, Lepik K, Luts K, Uibo O, Uibo R (2014) Low prevalence of IgA anti-transglutaminase 1, 2, and 3 autoantibodies in children with atopic dermatitis. BMC Res Notes 7:310PubMedPubMedCentralCrossRef
38.
Dhar S, Kanwar AJ, Deodhar SD (1997) Lack of antinuclear antibody in children with atopic dermatitis. Indian J Dermatol Venereol Leprol 63:5–8PubMed
39.
Higashi N, Niimi Y, Aoki M, Kawana S (2009) Clinical features of antinuclear antibody-positive patients with atopic dermatitis. J Nippon Med Sch 76:300–307PubMedCrossRef
40.
Ohkouchi K, Mizutani H, Tanaka M, Takahashi M, Nakashima K, Shimizu M (1999) Anti-elongation factor-1alpha autoantibody in adult atopic dermatitis patients. Int Immunol 11:1635–1640PubMedCrossRef
41.
Tada J, Toi Y, Yoshioka T, Fujiwara H, Arata J (1994) Antinuclear antibodies in patients with atopic dermatitis and severe facial lesions. Dermatology 189:38–40PubMedCrossRef
42.
Taniguchi Y, Yamakami A, Sakamoto T, Nakamura Y, Okada H, Tanaka H, Mizutani H, Shimizu M (1992) Positive antinuclear antibody in atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 176:62–64
43.
Ress K, Metskula K, Annus T, Putnik U, Lepik K, Luts K, Uibo O, Uibo R (2015) Antinuclear antibodies in atopic dermatitis: a cross-sectional study on 346 children. Int J Dermatol 54:24–28PubMedCrossRef
44.
Stalder JF, Taïeb A, Atherton DJ, Bieber P, Bonifazi E, Broberg A, Calza A, Coleman R, De Prost Y, Stalder JF, Gelmetti C, Cuannetti A, Harper J, Künz B, Lachapelle JM, Langeland T, Lever R, Oranje AP, Oueille-Roussel C, Revuz J et al (1993) Severity scoring of atopic dermatitis: the SCORAD index. Consensus report of the European task force on atopic dermatitis. Dermatology 186:23–31CrossRef
45.
Rajka G, Langeland T (1989) Grading of the severity of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 144:13–14
46.
47.
Hide M, Tanaka T, Yamamura Y, Koro O, Yamamoto S (2002) IgE-mediated hypersensitivity against human sweat antigen in patients with atopic dermatitis. Acta Derm Venereol 82:335–340PubMedCrossRef
48.
Kinaciyan T, Natter S, Kraft D, Stingl G, Valenta R (2002) IgE autoantibodies monitored in a patient with atopic dermatitis under cyclosporin A treatment reflect tissue damage. J Allergy Clin Immunol 109:717–719PubMedCrossRef
49.
Kohsaka T, Hiragun T, Ishii K, Hiragun M, Kamegashira A, Hide M (2018) Different hypersensitivities against homologous proteins of MGL_1304 in patients with atopic dermatitis. Allergol Int 67:103–108PubMedCrossRef
50.
Lucae S, Schmid-Grendelmeier P, Wuthrich B, Kraft D, Valenta R, Linhart B (2016) IgE responses to exogenous and endogenous allergens in atopic dermatitis patients under long-term systemic cyclosporine A treatment. Allergy 71:115–118PubMedCrossRef
51.
Tanaka A, Tanaka T, Suzuki H, Ishii K, Kameyoshi Y, Hide M (2006) Semi-purification of the immunoglobulin E-sweat antigen acting on mast cells and basophils in atopic dermatitis. Exp Dermatol 15:283–290PubMedCrossRef
52.
Lind SM, Kuylenstierna C, Moll M, Winqvist EDJ, Lundeberg O, Karlsson L, Johansson MA,MTL, Scheynius C, Sandberg A, Karlsson JK MC (2009) IL-18 skews the invariant NKT-cell population via autoreactive activation in atopic eczema. Eur J Immunol 39:2293–2301PubMedCrossRef
53.
Kapitein B, Aalberse JA, Klein MR, de Jager W, Hoekstra MO, Knol EF, Prakken BJ (2013) Recognition of self-heat shock protein 60 by T cells from patients with atopic dermatitis. Cell Stress Chaperones 18:87–95PubMedCrossRef
54.
Heratizadeh A, Mittermann I, Balaji H, Wichmann K, Niebuhr M, Valenta R, Werfel T (2011) The role of T-cell reactivity towards the autoantigen alpha-NAC in atopic dermatitis. Br J Dermatol 164:316–324PubMedCrossRef
55.
Zhang BX, Lyu JC, Liu HB, Feng DQ, Zhang DC, Bi XJ, Duan ZW, Ding G (2015) Attenuation of peripheral regulatory T-cell suppression of skin-homing CD8(+)T cells in atopic dermatitis. Yonsei Med J 56:196–203PubMedCrossRef
56.
Sugiyama H, Gyulai R, Toichi E, Garaczi E, Shimada S, Stevens SR, McCormick TS, Cooper KD (2005) Dysfunctional blood and target tissue CD4 + CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J Immunol 174:164–173PubMedCrossRef
57.
Zhang YY, Wang AX, Xu L, Shen N, Zhu J, Tu CX (2016) Characteristics of peripheral blood CD4 + CD25 + regulatory T cells and related cytokines in severe atopic dermatitis. Eur J Dermatol 26:240–246PubMedCrossRef
58.
Chen B, Ye T, Shao Y, Zhang J, Zhong Q, Hu X, Zhang W, Yu B (2013) Association between copy-number variations of the human histamine H4 receptor gene and atopic dermatitis in a Chinese population. Clin Exp Dermatol 38:295–300; quiz 300 – 291PubMedCrossRef
59.
Zhang M, Venable JD, Thurmond RL (2006) The histamine H4 receptor in autoimmune disease. Expert Opin Investig Drugs 15:1443–1452PubMedCrossRef
60.
Bieber T, D’Erme AM, Akdis CA, Traidl-Hoffmann C, Lauener R, Schappi G, Schmid-Grendelmeier P (2017) Clinical phenotypes and endophenotypes of atopic dermatitis: Where are we, and where should we go? J Allergy Clin Immunol 139:S58–S64PubMedCrossRef
Metadata
Title
Atopic dermatitis and autoimmunity: the occurrence of autoantibodies and their association with disease severity
Authors
James Holmes
Lucy C. Fairclough
Ian Todd
Publication date
01-04-2019
Publisher
Springer Berlin Heidelberg
Published in
Archives of Dermatological Research / Issue 3/2019
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-019-01890-4

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