2,492
Views
4
CrossRef citations to date
0
Altmetric
Dermatology

Targeting interleukin 4 and interleukin 13: a novel therapeutic approach in bullous pemphigoid

, , , &
Pages 1156-1170 | Received 08 May 2022, Accepted 03 Mar 2023, Published online: 31 Mar 2023

References

  • Zillikens D, Mascaro JM, Rose PA, et al. A highly sensitive enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid. J Invest Dermatol. 1997;109(5):679–683.
  • Di Zenzo G, Thoma-Uszynski S, Fontao L, et al. Multicenter prospective study of the humoral autoimmune response in bullous pemphigoid. Clin Immunol. 2008;128(3):415–426.
  • Thoma-Uszynski S, Uter W, Schwietzke S, et al. Autoreactive T and B cells from bullous pemphigoid (BP) patients recognize epitopes clustered in distinct regions of BP180 and BP230. J Immunol. 2006;176(3):2015–2023.
  • Amber KT, Murrell DF, Schmidt E, et al. Autoimmune subepidermal bullous diseases of the skin and mucosae: clinical features, diagnosis, and management. Clin Rev Allergy Immunol. 2018;54(1):26–51.
  • Giudice GJ, Wilske KC, Anhalt GJ, et al. Development of an ELISA to detect anti-BP180 autoantibodies in bullous pemphigoid and herpes gestationis. J Invest Dermatol. 1994;102(6):878–881.
  • Bağcı IS, Horváth ON, Ruzicka T, et al. Bullous pemphigoid. Autoimmun Rev. 2017;16(5):445–455.
  • Liu Z, Giudice GJ, Swartz SJ, et al. The role of complement in experimental bullous pemphigoid. J Clin Invest. 1995;95(4):1539–1544.
  • Sams WMJr., Gammon WR. Mechanism of lesion production in pemphigus and pemphigoid. J Am Acad Dermatol. 1982;6(4 Pt 1):431–452.
  • Patton T, Korman NJ. Bullous pemphigoid treatment review. Expert Opin Pharmacother. 2006;7(17):2403–2411.
  • Gooderham MJ, Hong HC, Eshtiaghi P, et al. Dupilumab: a review of its use in the treatment of atopic dermatitis. J Am Acad Dermatol. 2018;78(3 Suppl 1):S28–S36.
  • Beck LA, Thaçi D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371(2):130–139.
  • Russo R, Capurro N, Cozzani E, et al. Use of dupilumab in bullous pemphigoid: where are We now? J Clin Med. 2022;11(12):3367.
  • Abdat R, Waldman RA, de Bedout V, et al. Dupilumab as a novel therapy for bullous pemphigoid: a multicenter case series. J Am Acad Dermatol. 2020;83(1):46–52.
  • Zhang Y, Xu Q, Chen L, et al. Efficacy and safety of dupilumab in moderate-to-severe bullous pemphigoid. Front Immunol. 2021;12:738907.
  • Seyed Jafari SM, Feldmeyer L, Bossart S, et al. Case report: combination of omalizumab and dupilumab for recalcitrant bullous pemphigoid. Front Immunol. 2021;11:611549.
  • Kaye A, Gordon SC, Deverapalli SC, et al. Dupilumab for the treatment of recalcitrant bullous pemphigoid. JAMA Dermatol. 2018;154(10):1225–1226.
  • Wang M, Wang J, Shi B. Case report: dupilumab for the treatment of bullous pemphigoid. Dermatol Ther. 2022;35(7):e15541.
  • Li W, Cai S, Man X. The treatment of refractory atypical bullous pemphigoid with generalized eczema and intense pruritus with dupilumab. Dermatol Ther. 2022;35(2):e15243.
  • Yang J, Gao H, Zhang Z, et al. Dupilumab combined with low-dose systemic steroid therapy improves efficacy and safety for bullous pemphigoid. Dermatol Ther. 2022;35(8):e15648.
  • Shan Y, Zuo YG. A successful case of vesicular pemphigoid concurrent with pulmonary tuberculosis with dupilumab. Dermatol Ther. 2022;35(4):e15330.
  • Pop SR, Strock D, Smith RJ. Dupilumab for the treatment of pembrolizumab-induced bullous pemphigoid: a case report. Dermatol Ther. 2022;35(8):e15623.
  • Jendoubi F, Bost C, Tournier E, et al. Severe pemphigoid nodularis successfully treated with dupilumab. Dermatol Ther. 2022;35(9):e15727.
  • Bruni M, Moar A, Schena D, et al. A case of nivolumab-induced bullous pemphigoid successfully treated with dupilumab. Dermatol Online J. 2022;28(2):6.
  • Zhang Y, Zhang J, Chen J, et al. Dupilumab successfully treated refractory bullous pemphigoid with early clinical manifestations imitating atopic dermatitis: a case letter. Australas J Dermatol. 2021;62(4):525–527.
  • Saleh M, Reedy M, Torok H, et al. Successful treatment of bullous pemphigoid with dupilumab: a case and brief review of the literature. Dermatol Online J. 2021;27(4):7.
  • Klepper EM, Robinson HN. Dupilumab for the treatment of nivolumab-induced bullous pemphigoid: a case report and review of the literature. Dermatol Online J. 2021;27(9):6.
  • Seidman JS, Eichenfield DZ, Orme CM. Dupilumab for bullous pemphigoid with intractable pruritus. Dermatol Online J. 2019;25(11):12.
  • Cao P, Xu W, Zhang L. Rituximab, omalizumab, and dupilumab treatment outcomes in bullous pemphigoid: a systematic review. Front Immunol. 2022;13:928621.
  • Velin M, Dugourd PM, Sanchez A, et al. Efficacy and safety of methotrexate, omalizumab and dupilumab for bullous pemphigoid in patients resistant or contraindicated to oral steroids. A monocentric real-life study. J Eur Acad Dermatol Venereol. 2022;36(7):e539–e542.
  • Takamura S, Teraki Y. Treatment of bullous pemphigoid with dupilumab: dupilumab exerts its effect by primarily suppressing T-helper 2 cytokines. J Dermatol. 2022;49(9):845–850.
  • Bal A, Sorensen A, Ondreyco SM. Nonbullous erythrodermic pemphigoid with florid lymphadenopathy, response to dupilumab. JAAD Case Rep. 2021;17:58–60.
  • Liu X, Ma J, Qiu X, et al. Dupilumab, an emerging therapeutic choice for recalcitrant subepidermal autoimmune bullous diseases: a case series of three patients. Eur J Dermatol. 2021;31(6):846–847.
  • Valenti M, De Giacomo P, Lavecchia A, et al. A severe case of IgA bullous pemphigoid successfully treated with dupilumab. Dermatol Ther. 2022;35(11):e15890.
  • Sitaru C, Mihai S, Zillikens D. The relevance of the IgG subclass of autoantibodies for blister induction in autoimmune bullous skin diseases. Arch Dermatol Res. 2007;299(1):1–8.
  • Giomi B, Caproni M, Calzolari A, et al. Th1, Th2 and Th3 cytokines in the pathogenesis of bullous pemphigoid. J Dermatol Sci. 2002;30(2):116–128.
  • Dainichi T, Nishie W, Yamagami Y, et al. Bullous pemphigoid suggestive of complement-independent blister formation with anti-BP180 IgG4 autoantibodies. Br J Dermatol. 2016;175(1):187–190.
  • Hofmann S, Thoma-Uszynski S, Hunziker T, et al. Severity and phenotype of bullous pemphigoid relate to autoantibody profile against the NH2- and COOH-terminal regions of the BP180 ectodomain. J Invest Dermatol. 2002;119(5):1065–1073.
  • Mihai S, Chiriac MT, Herrero-Gonzalez JE, et al. IgG4 autoantibodies induce dermal-epidermal separation. J Cell Mol Med. 2007;11(5):1117–1128.
  • Zuo Y, Evangelista F, Culton D, et al. IgG4 autoantibodies are inhibitory in the autoimmune disease bullous pemphigoid. J Autoimmun. 2016;73:111–119.
  • Fairley JA, Burnett CT, Fu CL, et al. A pathogenic role for IgE in autoimmunity: bullous pemphigoid IgE reproduces the early phase of lesion development in human skin grafted to nu/nu mice. J Invest Dermatol. 2007;127(11):2605–2611.
  • Döpp R, Schmidt E, Chimanovitch I, et al. IgG4 and IgE are the major immunoglobulins targeting the NC16A domain of BP180 in bullous pemphigoid: serum levels of these immunoglobulins reflect disease activity. J Am Acad Dermatol. 2000;42(4):577–583.
  • Dresow SK, Sitaru C, Recke A, et al. IgE autoantibodies against the intracellular domain of BP180. Br J Dermatol. 2009;160(2):429–432.
  • Kalowska M, Ciepiela O, Kowalewski C, et al. Enzyme-linked immunoassay index for anti-NC16a IgG and IgE auto-antibodies correlates with severity and activity of bullous pemphigoid. Acta Derm Venereol. 2016;96(2):191–196.
  • Messingham KN, Holahan HM, Frydman AS, et al. Human eosinophils express the high affinity IgE receptor, FcepsilonRI, in bullous pemphigoid. PLOS One. 2014;9(9):e107725.
  • Freire PC, Muñoz CH, Stingl G. IgE autoreactivity in bullous pemphigoid: eosinophils and mast cells as major targets of pathogenic immune reactants. Br J Dermatol. 2017;177(6):1644–1653.
  • Messingham KN, Crowe TP, Fairley JA. The intersection of IgE autoantibodies and eosinophilia in the pathogenesis of bullous pemphigoid. Front Immunol. 2019;10:2331.
  • Zone JJ, Taylor T, Hull C, et al. IgE basement membrane zone antibodies induce eosinophil infiltration and histological blisters in engrafted human skin on SCID mice. J Invest Dermatol. 2007;127(5):1167–1174.
  • Messingham KN, Srikantha R, DeGueme AM, et al. FcR-independent effects of IgE and IgG autoantibodies in bullous pemphigoid. J Immunol. 2011;187(1):553–560.
  • Amber KT, Valdebran M, Kridin K, et al. The role of eosinophils in bullous pemphigoid: a developing model of eosinophil pathogenicity in mucocutaneous disease. Front Med. 2018;5:201.
  • Yu X, Holdorf K, Kasper B, et al. FcγRIIA and FcγRIIIB are required for autoantibody-induced tissue damage in experimental human models of bullous pemphigoid. J Invest Dermatol. 2010;130(12):2841–2844.
  • Lin L, Hwang BJ, Culton DA, et al. Eosinophils mediate tissue injury in the autoimmune skin disease bullous pemphigoid. J Invest Dermatol. 2018;138(5):1032–1043.
  • Bushkell LL, Jordon RE. Bullous pemphigoid: a cause of peripheral blood eosinophilia. J Am Acad Dermatol. 1983;8(5):648–651.
  • Giusti D, Gatouillat G, Le Jan S, et al. Eosinophil cationic protein (ECP), a predictive marker of bullous pemphigoid severity and outcome. Sci Rep. 2017;7(1):4833.
  • Simon D, Hoesli S, Roth N, et al. Eosinophil extracellular DNA traps in skin diseases. J Allergy Clin Immunol. 2011;127(1):194–199.
  • Bakker CV, Terra JB, Pas HH, et al. Bullous pemphigoid as pruritus in the elderly: a common presentation. JAMA Dermatol. 2013;149(8):950–953.
  • Hashimoto T, Kursewicz CD, Fayne RA, et al. Pathophysiologic mechanisms of itch in bullous pemphigoid. J Am Acad Dermatol. 2020;83(1):53–62.
  • Kowalski EH, Kneibner D, Kridin K, et al. Serum and blister fluid levels of cytokines and chemokines in pemphigus and bullous pemphigoid. Autoimmun Rev. 2019;18(5):526–534.
  • Rudrich U, Gehring M, Papakonstantinou E, et al. Eosinophils are a major source of interleukin-31 in bullous pemphigoid. Acta Derm Venereol. 2018;98(8):766–771.
  • Teraki Y, Hotta T, Shiohara T. Skin-homing interleukin-4 and -13-producing cells contribute to bullous pemphigoid: remission of disease is associated with increased frequency of interleukin-10-producing cells. J Invest Dermatol. 2001;117(5):1097–1102.
  • Rico MJ, Benning C, Weingart ES, et al. Characterization of skin cytokines in bullous pemphigoid and pemphigus vulgaris. Br J Dermatol. 1999;140(6):1079–1086.
  • Kubo M. T follicular helper and T(H)2 cells in allergic responses. Allergol Int. 2017;66(3):377–381.
  • Kabata H, Moro K, Koyasu S, et al. Group 2 innate lymphoid cells and asthma. Allergol Int. 2015;64(3):227–234.
  • Kabata H, Moro K, Fukunaga K, et al. Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation. Nat Commun. 2013;4:2675.
  • Bartemes KR, Kephart GM, Fox SJ, et al. Enhanced innate type 2 immune response in peripheral blood from patients with asthma. J Allergy Clin Immunol. 2014;134(3):671–678.e4.
  • Ebbo M, Crinier A, Vely F, et al. Innate lymphoid cells: major players in inflammatory diseases. Nat Rev Immunol. 2017;17(11):665–678.
  • Vijayanand P, Seumois G, Simpson LJ, et al. Interleukin-4 production by follicular helper T cells requires the conserved Il4 enhancer hypersensitivity site V. Immunity. 2012;36(2):175–187.
  • King IL, Mohrs M. IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells. J Exp Med. 2009;206(5):1001–1007.
  • Zou Y, Yuan H, Zhou S, et al. The pathogenic role of CD4(+) tissue-resident memory T cells bearing T follicular helper-like phenotype in pemphigus lesions. J Invest Dermatol. 2021;141(9):2141–2150.
  • Li Q, Liu Z, Dang E, et al. Follicular helper T cells (Tfh) and IL-21 involvement in the pathogenesis of bullous pemphigoid. PLOS One. 2013;8(7):e68145.
  • Junttila IS. Tuning the cytokine responses: an update on interleukin (IL)-4 and IL-13 receptor complexes. Front Immunol. 2018;9:888.
  • McCormick SM, Heller NM. Commentary: IL-4 and IL-13 receptors and signaling. Cytokine. 2015;75(1):38–50.
  • Sun XJ, Wang LM, Zhang Y, et al. Role of IRS-2 in insulin and cytokine signalling. Nature. 1995;377(6545):173–177.
  • Heller NM, Qi X, Gesbert F, et al. The extracellular and transmembrane domains of the gammaC and interleukin (IL)-13 receptor alpha1 chains, not their cytoplasmic domains, dictate the nature of signaling responses to IL-4 and IL-13. J Biol Chem. 2012;287(38):31948–31961.
  • Chandriani S, DePianto DJ, N’Diaye EN, et al. Endogenously expressed IL-13Ralpha2 attenuates IL-13-mediated responses but does not activate signaling in human lung fibroblasts. J Immunol. 2014;193(1):111–119.
  • Andrews AL, Nordgren IK, Campbell-Harding G, et al. The association of the cytoplasmic domains of interleukin 4 receptor alpha and interleukin 13 receptor alpha 2 regulates interleukin 4 signaling. Mol Biosyst. 2013;9(12):3009–3014.
  • Zheng T, Liu W, Oh SY, et al. IL-13 receptor alpha2 selectively inhibits IL-13-induced responses in the murine lung. J Immunol. 2008;180(1):522–529.
  • Hsieh CS, Heimberger AB, Gold JS, et al. Differential regulation of T helper phenotype development by interleukins 4 and 10 in an alpha beta T-cell-receptor transgenic system. Proc Natl Acad Sci USA. 1992;89(13):6065–6069.
  • Seder RA. Acquisition of lymphokine-producing phenotype by CD4+ T cells. J Allergy Clin Immunol. 1994;94(6 Pt 2):1195–1202.
  • Tavakolpour S, Tavakolpour V. Interleukin 4 inhibition as a potential therapeutic in pemphigus. Cytokine. 2016;77:189–195.
  • Matsunaga K, Katoh N, Fujieda S, et al. Dupilumab: basic aspects and applications to allergic diseases. Allergol Int. 2020;69(2):187–196.
  • Raap U, Gehring M, Kleiner S, et al. Human basophils are a source of and are differentially activated by IL-31. Clin Exp Allergy. 2017;47(4):499–508.
  • Miake S, Tsuji G, Takemura M, et al. IL-4 augments IL-31/IL-31 receptor alpha interaction leading to enhanced ccl 17 and ccl 22 production in dendritic cells: implications for atopic dermatitis. Int J Mol Sci. 2019;20(16):4053.
  • Datsi A, Steinhoff M, Ahmad F, et al. Interleukin-31: the “itchy” cytokine in inflammation and therapy. Allergy. 2021;76(10):2982–2997.
  • Feld M, Garcia R, Buddenkotte J, et al. The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves. J Allergy Clin Immunol. 2016;138(2):500–508.e24.
  • Salz M, Haeberle S, Hoffmann J, et al. Elevated IL-31 serum levels in bullous pemphigoid patients correlate with eosinophil numbers and are associated with BP180-IgE. J Dermatol Sci. 2017;87(3):309–311.
  • Hashimoto T, Rosen JD, Sanders KM, et al. Possible roles of basophils in chronic itch. Exp Dermatol. 2019;28(12):1373–1379.
  • Izuhara K, Arima K, Kanaji S, et al. IL-13: a promising therapeutic target for bronchial asthma. Curr Med Chem. 2006;13(19):2291–2298.
  • Oetjen LK, Mack MR, Feng J, et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell. 2017;171(1):217–228 e13.
  • Ameglio F, D’Auria L, Bonifati C, et al. Cytokine pattern in blister fluid and serum of patients with bullous pemphigoid: relationships with disease intensity. Br J Dermatol. 1998;138(4):611–614.
  • Hammad H, Lambrecht BN. The basic immunology of asthma. Cell. 2021;184(6):1469–1485.
  • Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(4s):S65–S76.
  • Wollenberg A, Blauvelt A, Guttman-Yassky E, et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br J Dermatol. 2021;184(3):437–449.
  • Guttman-Yassky E, Blauvelt A, Eichenfield LF, et al. Efficacy and safety of lebrikizumab, a high-affinity interleukin 13 inhibitor, in adults with moderate to severe atopic dermatitis: a phase 2b randomized clinical trial. JAMA Dermatol. 2020;156(4):411–420.
  • Ultsch M, Bevers J, Nakamura G, et al. Structural basis of signaling blockade by anti-IL-13 antibody lebrikizumab. J Mol Biol. 2013;425(8):1330–1339.
  • Miyano T, Irvine AD, Tanaka RJ. A mathematical model to identify optimal combinations of drug targets for dupilumab poor responders in atopic dermatitis. Allergy. 2022;77(2):582–594.
  • Karo-Atar D, Bitton A, Benhar I, et al. Therapeutic targeting of the interleukin-4/interleukin-13 signaling pathway: in allergy and beyond. BioDrugs. 2018;32(3):201–220.
  • Brombacher TM, Nono JK, De Gouveia KS, et al. IL-13-Mediated regulation of learning and memory. J Immunol. 2017;198(7):2681–2688.
  • Derecki NC, Cardani AN, Yang CH, et al. Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med. 2010;207(5):1067–1080.
  • Zhao W, Wang Y, Mao X, et al. Detection of underlying dementia in bullous pemphigoid patients using cognitive evaluation tests: a multicenter case-control study. Ann Transl Med. 2020;8(21):1397.
  • Papakonstantinou E, Limberg MM, Gehring M, et al. Neurological disorders are associated with bullous pemphigoid. J Eur Acad Dermatol Venereol. 2019;33(5):925–929.
  • Kokkonen N, Herukka SK, Huilaja L, et al. Increased levels of the bullous pemphigoid BP180 autoantibody are associated with more severe dementia in Alzheimer’s disease. J Invest Dermatol. 2017;137(1):71–76.
  • Nation DA, Sweeney MD, Montagne A, et al. Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat Med. 2019;25(2):270–276.
  • Braddock M, Hanania NA, Sharafkhaneh A, et al. Potential risks related to modulating interleukin-13 and interleukin-4 signalling: a systematic review. Drug Saf. 2018;41(5):489–509.