Bullous pemphigoid anti-BP180-NC16A autoantibody reactivity in healthy individuals is associated with marked hypovitaminosis D and Th2-like cytokine predominance
Autoimmune bullous disease autoantibodies, particularly including bullous pemphigoid (BP)-related anti-BP180-NC16A IgG, have been reported in a small subset of healthy individuals, but information about associated factors is lacking. We hypothesized that an abnormal status of immunomodulatory vitami...
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Published in | Archives of Dermatological Research Vol. 315; no. 10; pp. 2921 - 2926 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Berlin/Heidelberg
Springer Berlin Heidelberg
01.12.2023
Springer Nature B.V |
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ISSN | 1432-069X 0340-3696 1432-069X |
DOI | 10.1007/s00403-022-02386-4 |
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Abstract | Autoimmune bullous disease autoantibodies, particularly including bullous pemphigoid (BP)-related anti-BP180-NC16A IgG, have been reported in a small subset of healthy individuals, but information about associated factors is lacking. We hypothesized that an abnormal status of immunomodulatory vitamin D could play a role in anti-BP180-NC16A autoantibody reactivity in healthy persons. In addition, we aimed to evaluate the cytokine profile associated with these autoantibodies. Plasma samples from 34 anti-BP180-NC16A IgG-reactive and 85 anti-BP180-NC16A IgG-negative healthy blood donors were tested for levels of 25-hydroxyvitamin D [25(OH)D] and a wide range of cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ, and TNF-α). We observed that anti-BP180-NC16A IgG-reactive healthy subjects had significantly lower plasma 25(OH)D levels and about a two-fold higher rate of vitamin D deficiency (< 20 ng/ml) compared to anti-BP180-NC16A IgG-negative healthy persons. In addition, anti-BP180-NC16A IgG-positive samples were characterized by significantly higher levels of IL-2, IL-5, IL-9, IL-10, and IL-13 which were, however, not significantly associated with the vitamin D levels. Our results indicate that healthy individuals with BP autoantibody reactivity share similarities with BP patients regarding the vitamin D status and cytokine profile (i.e., marked hypovitaminosis D and Th2 predominance), which may have pathophysiologic implications. |
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AbstractList | Autoimmune bullous disease autoantibodies, particularly including bullous pemphigoid (BP)-related anti-BP180-NC16A IgG, have been reported in a small subset of healthy individuals, but information about associated factors is lacking. We hypothesized that an abnormal status of immunomodulatory vitamin D could play a role in anti-BP180-NC16A autoantibody reactivity in healthy persons. In addition, we aimed to evaluate the cytokine profile associated with these autoantibodies. Plasma samples from 34 anti-BP180-NC16A IgG-reactive and 85 anti-BP180-NC16A IgG-negative healthy blood donors were tested for levels of 25-hydroxyvitamin D [25(OH)D] and a wide range of cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ, and TNF-α). We observed that anti-BP180-NC16A IgG-reactive healthy subjects had significantly lower plasma 25(OH)D levels and about a two-fold higher rate of vitamin D deficiency (< 20 ng/ml) compared to anti-BP180-NC16A IgG-negative healthy persons. In addition, anti-BP180-NC16A IgG-positive samples were characterized by significantly higher levels of IL-2, IL-5, IL-9, IL-10, and IL-13 which were, however, not significantly associated with the vitamin D levels. Our results indicate that healthy individuals with BP autoantibody reactivity share similarities with BP patients regarding the vitamin D status and cytokine profile (i.e., marked hypovitaminosis D and Th2 predominance), which may have pathophysiologic implications. Autoimmune bullous disease autoantibodies, particularly including bullous pemphigoid (BP)-related anti-BP180-NC16A IgG, have been reported in a small subset of healthy individuals, but information about associated factors is lacking. We hypothesized that an abnormal status of immunomodulatory vitamin D could play a role in anti-BP180-NC16A autoantibody reactivity in healthy persons. In addition, we aimed to evaluate the cytokine profile associated with these autoantibodies. Plasma samples from 34 anti-BP180-NC16A IgG-reactive and 85 anti-BP180-NC16A IgG-negative healthy blood donors were tested for levels of 25-hydroxyvitamin D [25(OH)D] and a wide range of cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ, and TNF-α). We observed that anti-BP180-NC16A IgG-reactive healthy subjects had significantly lower plasma 25(OH)D levels and about a two-fold higher rate of vitamin D deficiency (< 20 ng/ml) compared to anti-BP180-NC16A IgG-negative healthy persons. In addition, anti-BP180-NC16A IgG-positive samples were characterized by significantly higher levels of IL-2, IL-5, IL-9, IL-10, and IL-13 which were, however, not significantly associated with the vitamin D levels. Our results indicate that healthy individuals with BP autoantibody reactivity share similarities with BP patients regarding the vitamin D status and cytokine profile (i.e., marked hypovitaminosis D and Th2 predominance), which may have pathophysiologic implications.Autoimmune bullous disease autoantibodies, particularly including bullous pemphigoid (BP)-related anti-BP180-NC16A IgG, have been reported in a small subset of healthy individuals, but information about associated factors is lacking. We hypothesized that an abnormal status of immunomodulatory vitamin D could play a role in anti-BP180-NC16A autoantibody reactivity in healthy persons. In addition, we aimed to evaluate the cytokine profile associated with these autoantibodies. Plasma samples from 34 anti-BP180-NC16A IgG-reactive and 85 anti-BP180-NC16A IgG-negative healthy blood donors were tested for levels of 25-hydroxyvitamin D [25(OH)D] and a wide range of cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ, and TNF-α). We observed that anti-BP180-NC16A IgG-reactive healthy subjects had significantly lower plasma 25(OH)D levels and about a two-fold higher rate of vitamin D deficiency (< 20 ng/ml) compared to anti-BP180-NC16A IgG-negative healthy persons. In addition, anti-BP180-NC16A IgG-positive samples were characterized by significantly higher levels of IL-2, IL-5, IL-9, IL-10, and IL-13 which were, however, not significantly associated with the vitamin D levels. Our results indicate that healthy individuals with BP autoantibody reactivity share similarities with BP patients regarding the vitamin D status and cytokine profile (i.e., marked hypovitaminosis D and Th2 predominance), which may have pathophysiologic implications. Autoimmune bullous disease autoantibodies, particularly including bullous pemphigoid (BP)-related anti-BP180-NC16A IgG, have been reported in a small subset of healthy individuals, but information about associated factors is lacking. We hypothesized that an abnormal status of immunomodulatory vitamin D could play a role in anti-BP180-NC16A autoantibody reactivity in healthy persons. In addition, we aimed to evaluate the cytokine profile associated with these autoantibodies. Plasma samples from 34 anti-BP180-NC16A IgG-reactive and 85 anti-BP180-NC16A IgG-negative healthy blood donors were tested for levels of 25-hydroxyvitamin D [25(OH)D] and a wide range of cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ, and TNF-α). We observed that anti-BP180-NC16A IgG-reactive healthy subjects had significantly lower plasma 25(OH)D levels and about a two-fold higher rate of vitamin D deficiency (< 20 ng/ml) compared to anti-BP180-NC16A IgG-negative healthy persons. In addition, anti-BP180-NC16A IgG-positive samples were characterized by significantly higher levels of IL-2, IL-5, IL-9, IL-10, and IL-13 which were, however, not significantly associated with the vitamin D levels. Our results indicate that healthy individuals with BP autoantibody reactivity share similarities with BP patients regarding the vitamin D status and cytokine profile (i.e., marked hypovitaminosis D and Th2 predominance), which may have pathophysiologic implications. |
Author | Ludwig, Ralf J. Tukaj, Stefan Zillikens, Detlef Kasperkiewicz, Michael Prüßmann, Jasper N. Schmidt, Enno Bieber, Katja Prüßmann, Wiebke |
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Cites_doi | 10.1016/j.jaad.2021.02.003 10.18388/abp.2020_2905 10.1080/09546634.2020.1810606 10.1210/jc.2011-0385 10.1136/ard.2010.148494 10.1016/j.jdermsci.2007.12.003 10.1186/s13023-015-0278-x 10.1177/0961203315584811 10.1111/jdv.12929 10.1111/exd.12445 10.1177/12034754211027858 10.3892/mmr.1.4.581 10.1016/j.jsbmb.2013.11.003 10.1056/NEJMoa021933 10.5152/tao.2015.1187 10.2147/JIR.S103298 10.1016/S0140-6736(12)61140-4 10.1016/j.jid.2017.09.009 10.1158/1055-9965.EPI-16-0339 10.3945/ajcn.115.120873 |
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Keywords | 25(OH)D Vitamin D Bullous pemphigoid Cytokine Th2 |
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References | Schmidt, Zillikens (CR5) 2013; 381 Prüßmann, Prüßmann, Recke (CR1) 2014; 23 Raneses, McGinley Simpson, Rosenberg, Coffman, Meyerle (CR4) 2022; 86 Yang, Wu, Zhao, Long, Lu (CR9) 2020 Ritterhouse, Crowe, Niewold (CR6) 2011; 70 Prüßmann, Prüßmann, Koga (CR2) 2015; 10 Belmesk, Muntyanu, Cantin (CR17) 2022; 26 Arbuckle, McClain, Rubertone (CR3) 2003; 349 Yamamoto, Tamai, Nakano (CR14) 2008; 50 Yamamoto, Tamai, Nakano (CR13) 2008; 1 Tukaj (CR8) 2020; 67 Cashman, Dowling, Škrabáková (CR16) 2016; 103 Tukaj, Grüner, Tukaj, Zillikens, Kasperkiewicz (CR11) 2016; 30 Keleş, Özkara, İlhan, Güngör, Karlıdağ, Yalçın (CR18) 2015; 53 Holick, Binkley, Bischoff-Ferrari (CR10) 2011; 96 Schneider, Colar da Silva, Werres Junior, Alegretti, Pereira dos Santos, Santos, Sassi, Heemann, Pfaffenseller, Tavares Brenol, Monticielo (CR19) 2015; 24 Tukaj, Bieber, Witte (CR12) 2018; 138 Palacios, Gonzalez (CR15) 2014; 144 Meier, Sandler, Simonsick, Parks (CR7) 2016; 25 Azizieh, Alyahya, Raghupathy (CR20) 2016; 9 MR Arbuckle (2386_CR3) 2003; 349 C Yamamoto (2386_CR13) 2008; 1 M Yang (2386_CR9) 2020 MF Holick (2386_CR10) 2011; 96 KD Cashman (2386_CR16) 2016; 103 L Belmesk (2386_CR17) 2022; 26 LL Ritterhouse (2386_CR6) 2011; 70 W Prüßmann (2386_CR2) 2015; 10 S Tukaj (2386_CR12) 2018; 138 E Raneses (2386_CR4) 2022; 86 L Schneider (2386_CR19) 2015; 24 E Schmidt (2386_CR5) 2013; 381 HC Meier (2386_CR7) 2016; 25 S Tukaj (2386_CR11) 2016; 30 C Yamamoto (2386_CR14) 2008; 50 J Prüßmann (2386_CR1) 2014; 23 S Tukaj (2386_CR8) 2020; 67 F Azizieh (2386_CR20) 2016; 9 C Palacios (2386_CR15) 2014; 144 E Keleş (2386_CR18) 2015; 53 |
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publication-title: J Steroid Biochem Mol Biol doi: 10.1016/j.jsbmb.2013.11.003 – volume: 349 start-page: 1526 issue: 16 year: 2003 end-page: 1533 ident: CR3 article-title: Development of autoantibodies before the clinical onset of systemic lupus erythematosus publication-title: N Engl J Med doi: 10.1056/NEJMoa021933 – volume: 53 start-page: 139 issue: 4 year: 2015 end-page: 143 ident: CR18 article-title: The relationship between Th1/Th2 balance and 1α, 25-dihydroxyvitamin D in patients with allergic rhinitis publication-title: Turk Arch Otorhinolaryngol doi: 10.5152/tao.2015.1187 – volume: 9 start-page: 51 year: 2016 end-page: 57 ident: CR20 article-title: Association between levels of vitamin D and inflammatory markers in healthy women publication-title: J Inflamm Res doi: 10.2147/JIR.S103298 – volume: 381 start-page: 320 issue: 9863 year: 2013 end-page: 332 ident: CR5 article-title: Pemphigoid diseases publication-title: Lancet doi: 10.1016/S0140-6736(12)61140-4 – volume: 138 start-page: 301 issue: 2 year: 2018 end-page: 309 ident: CR12 article-title: Calcitriol treatment ameliorates inflammation and blistering in mouse models of epidermolysis bullosa acquisita publication-title: J Invest Dermatol doi: 10.1016/j.jid.2017.09.009 – volume: 25 start-page: 1559 issue: 12 year: 2016 end-page: 1563 ident: CR7 article-title: Association between vitamin D deficiency and antinuclear antibodies in middle-aged and older U.S. adults publication-title: Cancer Epidemiol Biomarkers Prev doi: 10.1158/1055-9965.EPI-16-0339 – volume: 103 start-page: 1033 issue: 4 year: 2016 end-page: 1044 ident: CR16 article-title: Vitamin D deficiency in Europe: pandemic? publication-title: Am J Clin Nutr doi: 10.3945/ajcn.115.120873 – volume: 23 start-page: 519 issue: 7 year: 2014 ident: 2386_CR1 publication-title: Exp Dermatol doi: 10.1111/exd.12445 – volume: 24 start-page: 1191 issue: 11 year: 2015 ident: 2386_CR19 publication-title: Lupus doi: 10.1177/0961203315584811 – volume: 9 start-page: 51 year: 2016 ident: 2386_CR20 publication-title: J Inflamm Res doi: 10.2147/JIR.S103298 – volume: 50 start-page: 155 issue: 2 year: 2008 ident: 2386_CR14 publication-title: J Dermatol Sci doi: 10.1016/j.jdermsci.2007.12.003 – volume: 144 start-page: 138 issue: Pt A year: 2014 ident: 2386_CR15 publication-title: J Steroid Biochem Mol Biol doi: 10.1016/j.jsbmb.2013.11.003 – volume: 26 start-page: 33 issue: 1 year: 2022 ident: 2386_CR17 publication-title: J Cutan Med Surg doi: 10.1177/12034754211027858 – volume: 349 start-page: 1526 issue: 16 year: 2003 ident: 2386_CR3 publication-title: N Engl J Med doi: 10.1056/NEJMoa021933 – volume: 53 start-page: 139 issue: 4 year: 2015 ident: 2386_CR18 publication-title: Turk Arch Otorhinolaryngol doi: 10.5152/tao.2015.1187 – volume: 25 start-page: 1559 issue: 12 year: 2016 ident: 2386_CR7 publication-title: Cancer Epidemiol Biomarkers Prev doi: 10.1158/1055-9965.EPI-16-0339 – volume: 1 start-page: 581 issue: 4 year: 2008 ident: 2386_CR13 publication-title: Mol Med Rep doi: 10.3892/mmr.1.4.581 – volume: 103 start-page: 1033 issue: 4 year: 2016 ident: 2386_CR16 publication-title: Am J Clin Nutr doi: 10.3945/ajcn.115.120873 – volume: 86 start-page: 237 issue: 1 year: 2022 ident: 2386_CR4 publication-title: J Am Acad Dermatol doi: 10.1016/j.jaad.2021.02.003 – volume: 67 start-page: 1 issue: 1 year: 2020 ident: 2386_CR8 publication-title: Acta Biochim Pol doi: 10.18388/abp.2020_2905 – volume: 10 start-page: 63 year: 2015 ident: 2386_CR2 publication-title: Orphanet J Rare Dis doi: 10.1186/s13023-015-0278-x – volume: 138 start-page: 301 issue: 2 year: 2018 ident: 2386_CR12 publication-title: J Invest Dermatol doi: 10.1016/j.jid.2017.09.009 – volume: 70 start-page: 1569 issue: 9 year: 2011 ident: 2386_CR6 publication-title: Ann Rheum Dis doi: 10.1136/ard.2010.148494 – volume: 381 start-page: 320 issue: 9863 year: 2013 ident: 2386_CR5 publication-title: Lancet doi: 10.1016/S0140-6736(12)61140-4 – year: 2020 ident: 2386_CR9 publication-title: J Dermatolog Treat doi: 10.1080/09546634.2020.1810606 – volume: 96 start-page: 1911 issue: 7 year: 2011 ident: 2386_CR10 publication-title: J Clin Endocrinol Metab doi: 10.1210/jc.2011-0385 – volume: 30 start-page: 288 issue: 2 year: 2016 ident: 2386_CR11 publication-title: J Eur Acad Dermatol Venereol doi: 10.1111/jdv.12929 |
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SubjectTerms | 25-Hydroxyvitamin D Autoantibodies Blood donors Bullous diseases Bullous pemphigoid Concise Communications Cytokines Dermatology Immunoglobulin G Immunomodulation Interleukin 10 Interleukin 13 Interleukin 2 Interleukin 5 Interleukin 9 Lymphocytes T Medicine Medicine & Public Health Tumor necrosis factor-α Vitamin D Vitamin deficiency γ-Interferon |
Title | Bullous pemphigoid anti-BP180-NC16A autoantibody reactivity in healthy individuals is associated with marked hypovitaminosis D and Th2-like cytokine predominance |
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