B Cells and Autoantibodies in AIRE Deficiency
Abstract
:1. Introduction
2. B Cell’s Contribution to APS-1 and Aire Deficiency
3. Thymic B Cells and Their Interaction with Developing T Cells
4. Loss of Aire and the Consequences for B Cells Ex-Thymus
5. Autoantibodies in APS-1
Clinical Manifestation | Autoantigen | Ref |
---|---|---|
Chronic mucocutaneous candidiasis | IL-22, IL-17 | [60,61] |
Hypoparathyroidism | NALP5, CaSR | [62,63] |
Addison’s disease | 21OH | [64,65] |
Ovarian failure | SSC, 17OH, NALP5 | [66,67] |
Testicular failure | TSGA1, TGM4, PDILT, MAGEB2, SSC | [68,69,70] |
Type 1 diabetes | Insulin, IA2 | [71] |
Autoimmune hepatitis | CYP1A2, AADC, TPH | [72,73,74] |
Intestinal malabsorption | TPH | [72,74] |
Vitiligo | SOX-9, SOX-10, AADC | [75,76] |
Alopecia | TH | [77] |
Pulmonary disease | KCNRG, BPIFB1 | [78,79] |
Non-organ specific | IFN-ω, IFN-α2, IL-22, IL-17 | [60,61,80] |
6. B Cells in AIRE-Deficient Mice Varies with Genetic Strain and Aire Mutations
7. Lessons from Other Autoimmune Diseases
8. Treatment Approaches Targeting B Cells in Autoimmune Diseases
9. Conclusions and Future Perspectives
- What is the inflammatory cytokine secretion profile of B cells in APS-1 patients?
- How do B cells in APS-1 patients interact with T cells, DCs, and macrophages, especially with regards to antigen presentation?
- Is the Breg subset functional in APS-1?
- Are the hallmark autoantibodies in plasma and sera from APS-1 patients pathogenic?
- Does B cell depletion therapy improve the main manifestations, and does it impact the interferon profile?
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Husebye, E.S.; Anderson, M.S.; Kämpe, O. Autoimmune Polyendocrine Syndromes. N. Engl. J. Med. 2018, 378, 1132–1141. [Google Scholar] [CrossRef]
- Wolff, A.S.B.; Erichsen, M.M.; Meager, A.; Magitta, N.F.; Myhre, A.G.; Bollerslev, J.; Fougner, K.J.; Lima, K.; Knappskog, P.M.; Husebye, E.S. Autoimmune Polyendocrine Syndrome Type 1 in Norway: Phenotypic Variation, Autoantibodies, and Novel Mutations in the Autoimmune Regulator Gene. J. Clin. Endocrinol. Metab. 2007, 92, 595–603. [Google Scholar] [CrossRef] [Green Version]
- Ahonen, P.; Myllärniemi, S.; Sipilä, I.; Perheentupa, J. Clinical Variation of Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy (APECED) in a Series of 68 Patients. N. Engl. J. Med. 1990, 322, 1829–1836. [Google Scholar] [CrossRef]
- Perheentupa, J. Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy. J. Clin. Endocrinol. Metab. 2006, 91, 2843–2850. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zlotogora, J.; Shapiro, M.S. Polyglandular autoimmune syndrome type I among Iranian Jews. J. Med. Genet. 1992, 29, 824–826. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guo, C.-J.; Leung, P.S.; Zhang, W.; Ma, X.; Gershwin, M.E. The immunobiology and clinical features of type 1 autoimmune polyglandular syndrome (APS-1). Autoimmun. Rev. 2018, 17, 78–85. [Google Scholar] [CrossRef]
- Meloni, A.; Furcas, M.; Cetani, F.; Marcocci, C.; Falorni, A.; Perniola, R.; Pura, M.; Wolff, A.S.B.; Husebye, E.S.; Lilic, D.; et al. Autoantibodies against Type I Interferons as an Additional Diagnostic Criterion for Autoimmune Polyendocrine Syndrome Type I. J. Clin. Endocrinol. Metab. 2008, 93, 4389–4397. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aaltonen, J.; Björses, P.; Perheentupa, J.; Horelli–Kuitunen, N.; Palotie, A.; Peltonen, L.; Lee, Y.S.; Francis, F.; Henning, S.; Thiel, C.; et al. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat. Genet. 1997, 17, 399–403. [Google Scholar] [CrossRef]
- Nagamine, K.; Peterson, P.; Scott, H.; Kudoh, J.; Minoshima, S.; Heino, M.; Krohn, K.J.E.; Lalioti, M.D.; Mullis, P.E.; Antonarakis, S.; et al. Positional cloning of the APECED gene. Nat. Genet. 1997, 17, 393–398. [Google Scholar] [CrossRef]
- Oftedal, B.; Hellesen, A.; Erichsen, M.M.; Bratland, E.; Vardi, A.; Perheentupa, J.; Kemp, E.H.; Fiskerstrand, T.; Viken, M.K.; Weetman, A.P.; et al. Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases. Immunity 2015, 42, 1185–1196. [Google Scholar] [CrossRef] [Green Version]
- Cetani, F.; Barbesino, G.; Borsari, S.; Pardi, E.; Cianferotti, L.; Pinchera, A.; Marcocci, C. A Novel Mutation of the Autoimmune Regulator Gene in an Italian Kindred with Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy, Acting in a Dominant Fashion and Strongly Cosegregating with Hypothyroid Autoimmune Thyroiditis. J. Clin. Endocrinol. Metab. 2001, 86, 4747–4752. [Google Scholar] [CrossRef]
- Abramson, J.; Husebye, E.S. Autoimmune regulator and self-tolerance - molecular and clinical aspects. Immunol. Rev. 2016, 271, 127–140. [Google Scholar] [CrossRef]
- Bruserud, Ø.; Oftedal, B.E.; Wolff, A.B.; Husebye, E.S. AIRE-mutations and autoimmune disease. Curr. Opin. Immunol. 2016, 43, 8–15. [Google Scholar] [CrossRef] [PubMed]
- Björses, P.; Halonen, M.; Palvimo, J.; Kolmer, M.; Aaltonen, J.; Ellonen, P.; Perheentupa, J.; Ulmanen, I.; Peltonen, L. Mutations in the AIRE Gene: Effects on Subcellular Location and Transactivation Function of the Autoimmune Polyendocrinopathy-Candidiasis–Ectodermal Dystrophy Protein. Am. J. Hum. Genet. 2000, 66, 378–392. [Google Scholar] [CrossRef] [Green Version]
- Stolarski, B.; Pronicka, E.; Korniszewski, L.; Pollak, A.; Kostrzewa, G.; Rowińska, E.; Włodarski, P.; Skórka, A.; Gremida, M.; Krajewski, P.; et al. Molecular background of polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome in a Polish population: Novel AIRE mutations and an estimate of disease prevalence. Clin. Genet. 2006, 70, 348–354. [Google Scholar] [CrossRef]
- Pearce, S.H.; Cheetham, T.; Imrie, H.; Vaidya, B.; Barnes, N.D.; Bilous, R.W.; Carr, D.; Meeran, K.; Shaw, N.J.; Smith, C.S.; et al. A Common and Recurrent 13-bp Deletion in the Autoimmune Regulator Gene in British Kindreds with Autoimmune Polyendocrinopathy Type 1. Am. J. Hum. Genet. 1998, 63, 1675–1684. [Google Scholar] [CrossRef] [Green Version]
- Goodnow, C.; Sprent, J.; Groth, B.F.D.S.; Vinuesa, C. Cellular and genetic mechanisms of self tolerance and autoimmunity. Nat. Cell Biol. 2005, 435, 590–597. [Google Scholar] [CrossRef] [PubMed]
- Anderson, M.S.; Venanzi, E.; Chen, Z.; Berzins, S.P.; Benoist, C.; Mathis, D. The Cellular Mechanism of Aire Control of T Cell Tolerance. Immunity 2005, 23, 227–239. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takahama, Y. Journey through the thymus: Stromal guides for T-cell development and selection. Nat. Rev. Immunol. 2006, 6, 127–135. [Google Scholar] [CrossRef] [PubMed]
- Anderson, M.S.; Venanzi, E.S.; Klein, L.; Chen, Z.; Berzins, S.P.; Turley, S.J.; von Boehmer, H.; Bronson, R.; Dierich, A.; Benoist, C.; et al. Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein. Science 2002, 298, 1395–1401. [Google Scholar] [CrossRef] [Green Version]
- Sansom, S.N.; Shikama-Dorn, N.; Zhanybekova, S.; Nusspaumer, G.; Macaulay, I.; Deadman, M.E.; Heger, A.; Ponting, C.; Holländer, G.A. Population and single-cell genomics reveal theAiredependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia. Genome Res. 2014, 24, 1918–1931. [Google Scholar] [CrossRef] [Green Version]
- Cowan, J.E.; Baik, S.; McCarthy, N.I.; Parnell, S.M.; White, A.J.; Jenkinson, W.E.; Anderson, G. Aire controls the recirculation of murine Foxp3+regulatory T-cells back to the thymus. Eur. J. Immunol. 2018, 48, 844–854. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Malchow, S.; Leventhal, D.S.; Lee, V.; Nishi, S.; Socci, N.D.; Savage, P.A. Aire Enforces Immune Tolerance by Directing Autoreactive T Cells into the Regulatory T Cell Lineage. Immunity 2016, 44, 1102–1113. [Google Scholar] [CrossRef] [Green Version]
- Yang, S.; Fujikado, N.; Kolodin, D.; Benoist, C.; Mathis, D. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance. Science 2015, 348, 589–594. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, X.; Li, X.C.; Xiao, X.; Sun, R.; Tian, Z.; Wei, H. CD4+CD62L+ Central Memory T Cells Can Be Converted to Foxp3+ T Cells. PLoS ONE 2013, 8, e77322. [Google Scholar] [CrossRef] [Green Version]
- Sng, J.; Ayoglu, B.; Chen, J.W.; Schickel, J.-N.; Ferre, E.M.N.; Glauzy, S.; Romberg, N.; Hoenig, M.; Cunningham-Rundles, C.; Utz, P.J.; et al. AIRE expression controls the peripheral selection of autoreactive B cells. Sci. Immunol. 2019, 4, eaav6778. [Google Scholar] [CrossRef]
- Koivula, T.-T.; Laakso, S.M.; Niemi, H.J.; Kekäläinen, E.; Laine, P.; Paulin, L.; Auvinen, P.; Arstila, T.P. Clonal Analysis of Regulatory T Cell Defect in Patients with Autoimmune Polyendocrine Syndrome Type 1 Suggests Intrathymic Impairment. Scand. J. Immunol. 2017, 86, 221–228. [Google Scholar] [CrossRef] [PubMed]
- Gies, V.; Guffroy, A.; Danion, F.; Billaud, P.; Keime, C.; Fauny, J.-D.; Susini, S.; Soley, A.; Martin, T.; Pasquali, J.-L.; et al. B cells differentiate in human thymus and express AIRE. J. Allergy Clin. Immunol. 2017, 139, 1049–1052.e12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yamano, T.; Nedjic, J.; Hinterberger, M.; Steinert, M.; Koser, S.; Pinto, S.; Gerdes, N.; Lutgens, E.; Ishimaru, N.; Busslinger, M.; et al. Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell Tolerance Induction. Immunity 2015, 42, 1048–1061. [Google Scholar] [CrossRef] [Green Version]
- Suzuki, E.; Kobayashi, Y.; Kawano, O.; Endo, K.; Haneda, H.; Yukiue, H.; Sasaki, H.; Yano, M.; Maeda, M.; Fujii, Y. Expression of AIRE in thymocytes and peripheral lymphocytes. Autoimmunity 2008, 41, 133–139. [Google Scholar] [CrossRef]
- Perri, V.; Gianchecchi, E.; Scarpa, R.; Valenzise, M.; Rosado, M.M.; Giorda, E.; Crinò, A.; Cappa, M.; Barollo, S.; Garelli, S.; et al. Altered B cell homeostasis and Toll-like receptor 9-driven response in patients affected by autoimmune polyglandular syndrome Type 1. Immunobiology 2017, 222, 372–383. [Google Scholar] [CrossRef] [PubMed]
- Zhao, B.; Chang, L.; Fu, H.; Sun, G.; Yang, W. The Role of Autoimmune Regulator (AIRE) in Peripheral Tolerance. J. Immunol. Res. 2018, 2018. [Google Scholar] [CrossRef]
- Zhu, W.; Yang, W.; He, Z.; Liao, X.; Wu, J.; Sun, J.; Yang, Y.; Li, Y. Overexpressing autoimmune regulator regulates the expression of toll-like receptors by interacting with their promoters in RAW264.7 cells. Cell. Immunol. 2011, 270, 156–163. [Google Scholar] [CrossRef] [PubMed]
- Gavanescu, I.; Benoist, C.; Mathis, D. B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients. Proc. Natl. Acad. Sci. USA 2008, 105, 13009–13014. [Google Scholar] [CrossRef] [Green Version]
- Popler, J.; Alimohammadi, M.; Kämpe, O.; Dalin, F.; Dishop, M.K.; Barker, J.M.; Moriarty-Kelsey, M.; Soep, J.B.; Deterding, R.R. Autoimmune polyendocrine syndrome type 1: Utility of KCNRG autoantibodies as a marker of active pulmonary disease and successful treatment with rituximab. Pediatr. Pulmonol. 2011, 47, 84–87. [Google Scholar] [CrossRef]
- Kato, A.; Hulse, K.; Tan, B.K.; Schleimer, R.P. B-lymphocyte lineage cells and the respiratory system. J. Allergy Clin. Immunol. 2013, 131, 933–957. [Google Scholar] [CrossRef] [Green Version]
- Napier, C.; Gan, E.H.; Mitchell, A.L.; Gilligan, L.C.; Rees, D.A.; Moran, C.; Chatterjee, K.; Vaidya, B.; James, R.A.; Mamoojee, Y.; et al. Residual Adrenal Function in Autoimmune Addison’s Disease—Effect of Dual Therapy With Rituximab and Depot Tetracosactide. J. Clin. Endocrinol. Metab. 2019, 105, e1250–e1259. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pearce, S.H.S.; Mitchell, A.L.; Bennett, S.; King, P.; Chandran, S.; Nag, S.; Chen, S.; Smith, B.R.; Isaacs, J.; Vaidya, B. Adrenal Steroidogenesis after B Lymphocyte Depletion Therapy in New-Onset Addison’s Disease. J. Clin. Endocrinol. Metab. 2012, 97, E1927–E1932. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Devoss, J.J.; Shum, A.K.; Johannes, K.P.A.; Lu, W.; Krawisz, A.K.; Wang, P.; Yang, T.; LeClair, N.P.; Austin, C.; Strauss, E.C.; et al. Effector Mechanisms of the Autoimmune Syndrome in the Murine Model of Autoimmune Polyglandular Syndrome Type 1. J. Immunol. 2008, 181, 4072–4079. [Google Scholar] [CrossRef] [Green Version]
- Delves, P.J.; Roitt, I.M. The Immune System. N. Engl. J. Med. 2000, 343, 108–117. [Google Scholar] [CrossRef]
- Petersone, L.; Edner, N.M.; Ovcinnikovs, V.; Heuts, F.; Ross, E.M.; Ntavli, E.; Wang, C.J.; Walker, L.S.K. T Cell/B Cell Collaboration and Autoimmunity: An Intimate Relationship. Front. Immunol. 2018, 9, 1941. [Google Scholar] [CrossRef]
- Akashi, K.; Richie, L.I.; Miyamoto, T.; Carr, W.H.; Weissman, I.L. B Lymphopoiesis in the Thymus. J. Immunol. 2000, 164, 5221–5226. [Google Scholar] [CrossRef]
- Ceredig, R. The ontogeny of B cells in the thymus of normal, CD3ε knockout (KO), RAG-2 KO and IL-7 transgenic mice. Int. Immunol. 2002, 14, 87–99. [Google Scholar] [CrossRef] [Green Version]
- Isaacson, P.; Norton, A.; Addis, B. The human thymus contains a novel population of B lymphocytes. Lancet 1987, 330, 1488–1491. [Google Scholar] [CrossRef]
- Miyama-Inaba, M.; Kuma, S.; Inaba, K.; Ogata, H.; Iwai, H.; Yasumizu, R.; Muramatsu, S.; Steinman, R.M.; Ikehara, S. Unusual phenotype of B cells in the thymus of normal mice. J. Exp. Med. 1988, 168, 811–816. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mori, S.; Inaba, M.; Sugihara, A.; Taketani, S.; Doi, H.; Fukuba, Y.; Yamamoto, Y.; Adachi, Y.; Inaba, K.; Fukuhara, S.; et al. Presence of B cell progenitors in the thymus. J. Immunol. 1997, 158, 4193–4199. [Google Scholar]
- Perera, J.; Meng, L.; Meng, F.; Huang, H. Autoreactive thymic B cells are efficient antigen-presenting cells of cognate self-antigens for T cell negative selection. Proc. Natl. Acad. Sci. USA 2013, 110, 17011–17016. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Walters, S.N.; Webster, K.E.; Daley, S.; Grey, S.T. A Role for Intrathymic B Cells in the Generation of Natural Regulatory T Cells. J. Immunol. 2014, 193, 170–176. [Google Scholar] [CrossRef] [PubMed]
- Xing, C.; Ma, N.; Xiaoqian, W.; Wang, X.; Zheng, M.; Han, G.; Chen, G.; Hou, C.; Shen, B.; Li, Y.; et al. Critical role for thymic CD19+CD5+CD1dhiIL-10+regulatory B cells in immune homeostasis. J. Leukoc. Biol. 2015, 97, 547–556. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cepeda, S.; Cantu, C.; Orozco, S.; Xiao, Y.; Brown, Z.; Semwal, M.K.; Venables, T.; Anderson, M.S.; Griffith, A.V. Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens. Cell Rep. 2018, 22, 1276–1287. [Google Scholar] [CrossRef] [Green Version]
- Nemazee, D. Mechanisms of central tolerance for B cells. Nat. Rev. Immunol. 2017, 17, 281–294. [Google Scholar] [CrossRef]
- Murphy, K.; Travers, P.; Walport, M. Janeway’s Immunobiology, 7th ed.; Garland Science/Taylor & Francis Group: New York, NY, USA, 1999; pp. 364–368. [Google Scholar]
- Tobón, G.J.; Izquierdo, J.H.; Cañas, C.A. B Lymphocytes: Development, Tolerance, and Their Role in Autoimmunity—Focus on Systemic Lupus Erythematosus. Autoimmune Dis. 2013, 2013. [Google Scholar] [CrossRef] [Green Version]
- Hässler, S.; Ramsey, C.; Karlsson, M.C.; Larsson, D.; Herrmann, B.; Rozell, B.; Backheden, M.; Peltonen, L.; Kämpe, O.; Winqvist, O. Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma. Blood 2006, 108, 1941–1948. [Google Scholar] [CrossRef] [Green Version]
- Lindh, E.; Lind, S.M.; Lindmark, E.; Hässler, S.; Perheentupa, J.; Peltonen, L.; Winqvist, O.; Karlsson, M.C.I. AIRE regulates T-cell-independent B-cell responses through BAFF. Proc. Natl. Acad. Sci. USA 2008, 105, 18466–18471. [Google Scholar] [CrossRef] [Green Version]
- Magnani, A.; Meloni, A.; Gattorno, M.; Martini, A.; Traggiai, E. B cell subsets phenotype in autoimmunity with immunodeficiency: Analysis of a cohort of patients with APECED syndrome. Pediatr. Rheumatol. 2011, 9, P285. [Google Scholar] [CrossRef] [Green Version]
- Wolff, A.S.B.; Oftedal, B.E.V.; Kisand, K.; Ersvaer, E.; Lima, K.; Husebye, E.S.; Ersvær, E. Flow Cytometry Study of Blood Cell Subtypes Reflects Autoimmune and Inflammatory Processes in Autoimmune Polyendocrine Syndrome Type I. Scand. J. Immunol. 2010, 71, 459–467. [Google Scholar] [CrossRef] [PubMed]
- Perniola, R.; Lobreglio, G.; Rosatelli, M.C.; Pitotti, E.; Accogli, E.; De Rinaldis, C. Immunophenotypic Characterisation of Peripheral Blood Lymphocytes in Autoimmune Polyglandular Syndrome Type 1: Clinical Study and Review of the Literature. J. Pediatr. Endocrinol. Metab. 2005, 18, 155–164. [Google Scholar] [CrossRef] [PubMed]
- Bruserud, Ø.; Oftedal, B.; Landegren, N.; Erichsen, M.M.; Bratland, E.; Lima, K.; Jørgensen, A.P.; Myhre, A.G.; Svartberg, J.; Fougner, K.J.; et al. A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 1. J. Clin. Endocrinol. Metab. 2016, 101, 2975–2983. [Google Scholar] [CrossRef]
- Kisand, K.; Wolff, A.S.B.; Podkrajsek, K.T.; Tserel, L.; Link, M.; Kisand, K.; Ersvaer, E.; Perheentupa, J.; Erichsen, M.M.; Bratanic, N.; et al. Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J. Exp. Med. 2010, 207, 299–308. [Google Scholar] [CrossRef] [PubMed]
- Puel, A.; Cypowyj, S.; Bustamante, J.; Wright, J.F.; Liu, L.; Lim, H.K.; Migaud, M.; Israel, L.; Chrabieh, M.; Audry, M.; et al. Chronic Mucocutaneous Candidiasis in Humans with Inborn Errors of Interleukin-17 Immunity. Science 2011, 332, 65–68. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alimohammadi, M.; Björklund, P.; Hallgren, Å.; Pöntynen, N.; Szinnai, G.; Shikama, N.; Keller, M.P.; Ekwall, O.; Kinkel, S.A.; Husebye, E.S.; et al. Autoimmune Polyendocrine Syndrome Type 1 and NALP5, a Parathyroid Autoantigen. N. Engl. J. Med. 2008, 358, 1018–1028. [Google Scholar] [CrossRef] [Green Version]
- Habibullah, M.; Porter, J.A.; Kluger, N.; Ranki, A.; Krohn, K.J.E.; Brandi, M.L.; Brown, E.M.; Weetman, A.P.; Kemp, E.H. Calcium-Sensing Receptor Autoantibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1: Epitopes, Specificity, Functional Affinity, IgG Subclass, and Effects on Receptor Activity. J. Immunol. 2018, 201, 3175–3183. [Google Scholar] [CrossRef] [Green Version]
- Winqvist, O.; Karlsson, F.; Kämpe, O. 21-hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet 1992, 339, 1559–1562. [Google Scholar] [CrossRef]
- Wolff, A.B.; Breivik, L.; Hufthammer, K.O.; Grytaas, M.A.; Bratland, E.; Husebye, E.S.; Oftedal, B.E. The natural history of 21-hydroxylase autoantibodies in autoimmune Addison’s disease. Eur. J. Endocrinol. 2021, 184, 607–615. [Google Scholar] [CrossRef]
- Brozzetti, A.; Alimohammadi, M.; Morelli, S.; Minarelli, V.; Hallgren, Å.; Giordano, R.; De Bellis, A.; Perniola, R.; Kämpe, O.; Falorni, A.; et al. Autoantibody Response Against NALP5/MATER in Primary Ovarian Insufficiency and in Autoimmune Addison’s Disease. J. Clin. Endocrinol. Metab. 2015, 100, 1941–1948. [Google Scholar] [CrossRef] [Green Version]
- Winqvist, O.; Gebre-Medhin, G.; Gustafsson, J.; Ritzén, E.M.; Lundkvist, O.; A Karlsson, F.; Kämpe, O. Identification of the main gonadal autoantigens in patients with adrenal insufficiency and associated ovarian failure. J. Clin. Endocrinol. Metab. 1995, 80, 1717–1723. [Google Scholar] [CrossRef]
- Fishman, D.; Kisand, K.; Hertel, C.; Rothe, M.; Remm, A.; Pihlap, M.; Adler, P.; Vilo, J.; Peet, A.; Meloni, A.; et al. Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins. Front. Immunol. 2017, 8, 976. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Landegren, N.; Sharon, N.; Freyhult, E.; Hallgren, Å.; Eriksson, D.; Edqvist, P.-H.; Bensing, S.; Wahlberg, J.; Nelson, L.M.; Gustafsson, J.; et al. Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1. Sci. Rep. 2016, 6, 20104. [Google Scholar] [CrossRef] [Green Version]
- Reimand, K.; Perheentupa, J.; Link, M.; Krohn, K.; Peterson, P.; Uibo, R. Testis-expressed protein TSGA10 - an auto-antigen in autoimmune polyendocrine syndrome type I. Int. Immunol. 2008, 20, 39–44. [Google Scholar] [CrossRef] [Green Version]
- Söderbergh, A.; Myhre, A.G.; Ekwall, O.; Gebre-Medhin, G.; Hedstrand, H.; Landgren, E.; Miettinen, A.; Eskelin, P.; Halonen, M.; Tuomi, T.; et al. Prevalence and Clinical Associations of 10 Defined Autoantibodies in Autoimmune Polyendocrine Syndrome Type I. J. Clin. Endocrinol. Metab. 2004, 89, 557–562. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ekwall, O.; Sjöberg, K.; Mirakian, R.; Rorsman, F.; Kämpe, O. Tryptophan hydroxylase autoantibodies and intestinal disease in autoimmune polyendocrine syndrome type 1. Lancet 1999, 354, 568. [Google Scholar] [CrossRef]
- Gebre-Medhin, G.; Husebye, E.; Gustafsson, J.; Winqvist, O.; Goksøyr, A.; Rorsman, F.; Kämpe, O. Cytochrome P450IA2 and aromaticl-amino acid decarboxylase are hepatic autoantigens in autoimmune polyendocrine syndrome type I. FEBS Lett. 1997, 412, 439–445. [Google Scholar] [CrossRef] [Green Version]
- Scarpa, R.; Alaggio, R.; Norberto, L.; Furmaniak, J.; Chen, S.; Smith, B.R.; Masiero, S.; Morlin, L.; Plebani, M.; De Luca, F.; et al. Tryptophan Hydroxylase Autoantibodies as Markers of a Distinct Autoimmune Gastrointestinal Component of Autoimmune Polyendocrine Syndrome Type 1. J. Clin. Endocrinol. Metab. 2013, 98, 704–712. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hedstrand, H.; Ekwall, O.; Olsson, M.J.; Landgren, E.; Kemp, E.H.; Weetman, A.P.; Perheentupa, J.; Husebye, E.; Gustafsson, J.; Betterle, C.; et al. The Transcription Factors SOX9 and SOX10 Are Vitiligo Autoantigens in Autoimmune Polyendocrine Syndrome Type I. J. Biol. Chem. 2001, 276, 35390–35395. [Google Scholar] [CrossRef] [Green Version]
- Husebye, E.S. Autoantibodies against Aromatic L-Amino Acid Decarboxylase in Autoimmune Polyendocrine Syndrome Type I. J. Clin. Endocrinol. Metab. 1997, 82, 147–150. [Google Scholar] [CrossRef]
- Hedstrand, H.; Ekwall, O.; Haavik, J.; Landgren, E.; Betterle, C.; Perheentupa, J.; Gustafsson, J.; Husebye, E.; Rorsman, F.; Kämpe, O. Identification of Tyrosine Hydroxylase as an Autoantigen in Autoimmune Polyendocrine Syndrome Type I. Biochem. Biophys. Res. Commun. 2000, 267, 456–461. [Google Scholar] [CrossRef]
- Alimohammadi, M.; Dubois, N.; Sköldberg, F.; Hallgren, Å.; Tardivel, I.; Hedstrand, H.; Haavik, J.; Husebye, E.S.; Gustafsson, J.; Rorsman, F.; et al. Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen. Proc. Natl. Acad. Sci. USA 2009, 106, 4396–4401. [Google Scholar] [CrossRef] [Green Version]
- Shum, A.K.; Alimohammadi, M.; Tan, C.L.; Cheng, M.H.; Metzger, T.C.; Law, C.S.; Lwin, W.; Perheentupa, J.; Bour-Jordan, H.; Carel, J.C.; et al. BPIFB1 Is a Lung-Specific Autoantigen Associated with Interstitial Lung Disease. Sci. Transl. Med. 2013, 5, 206ra139. [Google Scholar] [CrossRef] [Green Version]
- Meager, A.; Visvalingam, K.; Peterson, P.; Möll, K.; Murumägi, A.; Krohn, K.; Eskelin, P.; Perheentupa, J.; Husebye, E.; Kadota, Y.; et al. Anti-Interferon Autoantibodies in Autoimmune Polyendocrinopathy Syndrome Type 1. PLoS Med. 2006, 3, e289. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wolff, A.S.B.; Sarkadi, A.K.; Maródi, L.; Kärner, J.; Orlova, E.; Oftedal, B.E.V.; Kisand, K.; Olah, E.; Meloni, A.; Myhre, A.G.; et al. Anti-Cytokine Autoantibodies Preceding Onset of Autoimmune Polyendocrine Syndrome Type I Features in Early Childhood. J. Clin. Immunol. 2013, 33, 1341–1348. [Google Scholar] [CrossRef] [PubMed]
- Barzaghi, F.; Passerini, L. IPEX Syndrome: Improved Knowledge of Immune Pathogenesis Empowers Diagnosis. Front. Pediatr. 2021, 9, 612760. [Google Scholar] [CrossRef]
- Rosenberg, J.M.; Maccari, M.E.; Barzaghi, F.; Allenspach, E.J.; Pignata, C.; Weber, G.; Torgerson, T.R.; Utz, P.J.; Bacchetta, R. Neutralizing Anti-Cytokine Autoantibodies Against Interferon-α in Immunodysregulation Polyendocrinopathy Enteropathy X-Linked. Front. Immunol. 2018, 9, 544. [Google Scholar] [CrossRef]
- Bastard, P.; Rosen, L.B.; Zhang, Q.; Michailidis, E.; Hoffmann, H.-H.; Zhang, Y.; Dorgham, K.; Philippot, Q.; Rosain, J.; Béziat, V.; et al. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science 2020, 370, eabd4585. [Google Scholar] [CrossRef]
- Beccuti, G.; Ghizzoni, L.; Cambria, V.; Codullo, V.; Sacchi, P.; Lovati, E.; Mongodi, S.; Iotti, G.A.; Mojoli, F. A COVID-19 pneumonia case report of autoimmune polyendocrine syndrome type 1 in Lombardy, Italy: Letter to the editor. J. Endocrinol. Investig. 2020, 43, 1175–1177. [Google Scholar] [CrossRef]
- Cavadini, P.; Vermi, W.; Facchetti, F.; Fontana, S.; Nagafuchi, S.; Mazzolari, E.; Sediva, A.; Marrella, V.; Villa, A.; Fischer, A.; et al. AIRE deficiency in thymus of 2 patients with Omenn syndrome. J. Clin. Investig. 2005, 115, 728–732. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lemarquis, A.; Campbell, T.; Aranda-Guillén, M.; Hennings, V.; Brodin, P.; Kämpe, O.; Blennow, K.; Zetterberg, H.; Wennerås, C.; Eriksson, K.; et al. Severe COVID-19 in an APS1 patient with interferon autoantibodies treated with plasmapheresis. J. Allergy Clin. Immunol. 2021, 148, 96–98. [Google Scholar] [CrossRef] [PubMed]
- Meisel, C.; Akbil, B.; Meyer, T.; Lankes, E.; Corman, V.M.; Staudacher, O.; Unterwalder, N.; Kölsch, U.; Drosten, C.; Mall, M.A.; et al. Mild COVID-19 despite autoantibodies against type I IFNs in autoimmune polyendocrine syndrome type 1. J. Clin. Investig. 2021, 131. [Google Scholar] [CrossRef]
- Dawoodji, A.; Chen, J.-L.; Shepherd, D.; Dalin, F.; Tarlton, A.; Alimohammadi, M.; Penna-Martinez, M.; Meyer, G.; Mitchell, A.L.; Gan, E.H.; et al. High Frequency of Cytolytic 21-Hydroxylase–Specific CD8+ T Cells in Autoimmune Addison’s Disease Patients. J. Immunol. 2014, 193, 2118–2126. [Google Scholar] [CrossRef] [Green Version]
- Taniguchi, R.T.; DeVoss, J.J.; Moon, J.J.; Sidney, J.; Sette, A.; Jenkins, M.; Anderson, M.S. Detection of an autoreactive T-cell population within the polyclonal repertoire that undergoes distinct autoimmune regulator (Aire)-mediated selection. Proc. Natl. Acad. Sci. USA 2012, 109, 7847–7852. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Blechschmidt, K.; Schweiger, M.; Wertz, K.; Poulson, R.; Christensen, H.-M.; Rosenthal, A.; Lehrach, H.; Yaspo, M.-L. The Mouse Aire Gene: Comparative Genomic Sequencing, Gene Organization, and Expression. Genome Res. 1999, 9, 158–166. [Google Scholar]
- Wang, C.-Y.; Shi, J.-D.; Davoodi-Semiromi, A.; She, J.-X. Cloning ofAire, the Mouse Homologue of the Autoimmune Regulator (AIRE) Gene Responsible for Autoimmune Polyglandular Syndrome Type 1 (APS1). Genomics 1999, 55, 322–326. [Google Scholar] [CrossRef] [PubMed]
- Mathis, D.; Benoist, C. Aire. Annu. Rev. Immunol. 2009, 27, 287–312. [Google Scholar] [CrossRef] [PubMed]
- Ramsey, C.; Winqvist, O.; Puhakka, L.; Halonen, M.; Moro, A.; Kämpe, O.; Eskelin, P.; Pelto-Huikko, M.; Peltonen, L. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum. Mol. Genet. 2002, 11, 397–409. [Google Scholar] [CrossRef] [PubMed]
- Hubert, F.-X.; Kinkel, S.A.; Crewther, P.E.; Cannon, P.Z.F.; Webster, K.E.; Link, M.; Uibo, R.; O’Bryan, M.; Meager, A.; Forehan, S.P.; et al. Aire-Deficient C57BL/6 Mice Mimicking the Common Human 13-Base Pair Deletion Mutation Present with Only a Mild Autoimmune Phenotype. J. Immunol. 2009, 182, 3902–3918. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Su, M.; Giang, K.; Žumer, K.; Jiang, H.; Oven, I.; Rinn, J.; Devoss, J.J.; Johannes, K.P.A.; Lu, W.; Gardner, J.; et al. Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in Aire. J. Clin. Investig. 2008, 118, 1712–1726. [Google Scholar] [CrossRef] [PubMed]
- Goldfarb, Y.; Givony, T.; Kadouri, N.; Dobeš, J.; Peligero-Cruz, C.; Zalayat, I.; Damari, G.; Dassa, B.; Ben-Dor, S.; Gruper, Y.; et al. Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE autoregulation. J. Exp. Med. 2021, 218. [Google Scholar] [CrossRef]
- Pontynen, N.; Miettinen, A.; Arstila, T.P.; Kämpe, O.; Alimohammadi, M.; Vaarala, O.; Peltonen, L.; Ulmanen, I. Aire deficient mice do not develop the same profile of tissue-specific autoantibodies as APECED patients. J. Autoimmun. 2006, 27, 96–104. [Google Scholar] [CrossRef]
- Kojima, A.; Prehn, R.T. Genetic susceptibility to post-thymectomy autoimmune diseases in mice. Immunogenetics 1981, 14, 15–27. [Google Scholar] [CrossRef]
- Taguchi, O.; Nishizuka, Y.; Sakakura, T.; Kojima, A. Autoimmune oophoritis in thymectomized mice: Detection of circulating antibodies against oocytes. Clin. Exp. Immunol. 1980, 40, 540–553. [Google Scholar]
- Tun, K.S.K.; Setiady, Y.Y.; Samy, E.T.; Lewis, J.; Teuscher, C. Autoimmune Ovarian Disease in Day 3-Thymectomized Mice: The Neonatal Time Window, Antigen Specificity of Disease Suppression, and Genetic Control. Curr. Top. Microbiol. Immunol. 2005, 293, 209–247. [Google Scholar] [CrossRef]
- Shum, A.K.; DeVoss, J.; Tan, C.L.; Hou, Y.; Johannes, K.; O’Gorman, C.S.; Jones, K.D.; Sochett, E.B.; Fong, L.; Anderson, M.S. Identification of an Autoantigen Demonstrates a Link Between Interstitial Lung Disease and a Defect in Central Tolerance. Sci. Transl. Med. 2009, 1, 9ra20. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Puel, A.; Döffinger, R.; Natividad, A.; Chrabieh, M.; Morales, G.B.; Picard, C.; Cobat, A.; Ouachée-Chardin, M.; Toulon, A.; Bustamante, J.; et al. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J. Exp. Med. 2010, 207, 291–297. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kärner, J.; Meager, A.; Laan, M.; Maslovskaja, J.; Pihlap, M.; Remm, A.; Juronen, E.; Wolff, A.S.B.; Husebye, E.S.; Podkrajsek, K.T.; et al. Anti-cytokine autoantibodies suggest pathogenetic links with autoimmune regulator deficiency in humans and mice. Clin. Exp. Immunol. 2013, 171, 263–272. [Google Scholar] [CrossRef]
- Lee, D.S.W.; Rojas, O.L.; Gommerman, J.L. B cell depletion therapies in autoimmune disease: Advances and mechanistic insights. Nat. Rev. Drug Discov. 2021, 20, 179–199. [Google Scholar] [CrossRef]
- Ando, T.; Latif, R.; Davies, T. Thyrotropin receptor antibodies: New insights into their actions and clinical relevance. Best Pr. Res. Clin. Endocrinol. Metab. 2005, 19, 33–52. [Google Scholar] [CrossRef]
- Smith, B.R.; Sanders, J.; Furmaniak, J. TSH Receptor Antibodies. Thyroid 2007, 17, 923–938. [Google Scholar] [CrossRef]
- Howard, F.M.; Lennon, V.A.; Finley, J.; Matsumoto, J.; Elveback, L.R. Clinical Correlations of Antibodies That Bind, Block, or Modulate Human Acetylcholine Receptors in Myasthenia Gravis. Ann. N. Y. Acad. Sci. 1987, 505, 526–538. [Google Scholar] [CrossRef]
- Béland, K.; Marceau, G.; Labardy, A.; Bourbonnais, S.; Alvarez, F. Depletion of B cells induces remission of autoimmune hepatitis in mice through reduced antigen presentation and help to T cells. Hepatology 2015, 62, 1511–1523. [Google Scholar] [CrossRef]
- O’Neill, S.K.; Shlomchik, M.J.; Glant, T.T.; Cao, Y.; Doodes, P.D.; Finnegan, A. Antigen-Specific B Cells Are Required as APCs and Autoantibody-Producing Cells for Induction of Severe Autoimmune Arthritis. J. Immunol. 2005, 174, 3781–3788. [Google Scholar] [CrossRef]
- Wong, F.S.; Wen, L.; Tang, M.; Ramanathan, M.; Visintin, I.; Daugherty, J.; Hannum, L.G.; Janeway, C.A.; Shlomchik, M.J. Investigation of the role of B-cells in type 1 diabetes in the NOD mouse. Diabetes 2004, 53, 2581–2587. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Manca, F.; Fenoglio, D.; Kunkl, A.; Cambiaggi, C.; Sasso, M.; Celada, F. Differential activation of T cell clones stimulated by macrophages exposed to antigen complexed with monoclonal antibodies. A possible influence of paratope specificity on the mode of antigen processing. J. Immunol. 1988, 140, 2893–2898. [Google Scholar]
- Amigorena, S.; Bonnerot, C. Role of B-cell and Fc receptors in the selection of T-cell epitopes. Curr. Opin. Immunol. 1998, 10, 88–92. [Google Scholar] [CrossRef]
- Watts, C.; Lanzavecchia, A. Suppressive effect of antibody on processing of T cell epitopes. J. Exp. Med. 1993, 178, 1459–1463. [Google Scholar] [CrossRef] [Green Version]
- Harris, D.P.; Haynes, L.; Sayles, P.C.; Duso, D.K.; Eaton, S.M.; Lepak, N.M.; Johnson, L.L.; Swain, S.L.; Lund, F.E. Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat. Immunol. 2000, 1, 475–482. [Google Scholar] [CrossRef] [PubMed]
- Lund, F.E.; Garvy, B.A.; Randall, T.D.; Harris, D.P. Regulatory Roles for Cytokine- Producing B Cells in Infection and Autoimmune Disease; KARGER: Basel, Switzerland, 2004; Volume 8, pp. 25–54. [Google Scholar]
- Aloisi, F.; Borrell, R.P. Lymphoid neogenesis in chronic inflammatory diseases. Nat. Rev. Immunol. 2006, 6, 205–217. [Google Scholar] [CrossRef]
- Drayton, D.L.; Liao, S.; Mounzer, R.H.; Ruddle, N.H. Lymphoid organ development: From ontogeny to neogenesis. Nat. Immunol. 2006, 7, 344–353. [Google Scholar] [CrossRef]
- Fillatreau, S.; Sweenie, C.H.; McGeachy, M.J.; Gray, D.; Anderton, S.M. B cells regulate autoimmunity by provision of IL-10. Nat. Immunol. 2002, 3, 944–950. [Google Scholar] [CrossRef]
- Bouaziz, J.-D.; Yanaba, K.; Tedder, T.F. Regulatory B cells as inhibitors of immune responses and inflammation. Immunol. Rev. 2008, 224, 201–214. [Google Scholar] [CrossRef]
- Zhu, Q.; Rui, K.; Wang, S.; Tian, J. Advances of Regulatory B Cells in Autoimmune Diseases. Front. Immunol. 2021, 12, 592914. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Qin, Y.; Wang, X.; Zhang, L.; Wang, J.; Xu, X.; Chen, H.; Hsu, H.-T.; Zhang, M. Decrease in the proportion of CD24 hi CD38 hi B cells and impairment of their regulatory capacity in type 1 diabetes patients. Clin. Exp. Immunol. 2019, 200, 22–32. [Google Scholar] [CrossRef]
- Hussain, S.; Delovitch, T.L. Intravenous transfusion of BCR-activated B cells protects NOD mice from type 1 diabetes in an IL-10-dependent manner. J. Immunol. 2007, 179, 7225–7232. [Google Scholar] [CrossRef] [Green Version]
- Stożek, K.; Grubczak, K.; Marolda, V.; Eljaszewicz, A.; Moniuszko, M.; Bossowski, A. Lower proportion of CD19+IL-10+ and CD19+CD24+CD27+ but not CD1d+CD5+CD19+CD24+CD27+ IL-10+ B cells in children with autoimmune thyroid diseases. Autoimmunity 2019, 53, 46–55. [Google Scholar] [CrossRef]
- Peng, B.; Ming, Y.; Yang, C. Regulatory B cells: The cutting edge of immune tolerance in kidney transplantation. Cell Death Dis. 2018, 9, 1–13. [Google Scholar] [CrossRef]
- Watanabe, R.; Ishiura, N.; Nakashima, H.; Kuwano, Y.; Okochi, H.; Tamaki, K.; Sato, S.; Tedder, T.F.; Fujimoto, M. Regulatory B Cells (B10 Cells) Have a Suppressive Role in Murine Lupus: CD19 and B10 Cell Deficiency Exacerbates Systemic Autoimmunity. J. Immunol. 2010, 184, 4801–4809. [Google Scholar] [CrossRef] [PubMed]
- Evan, J.R.; Bozkurt, S.B.; Thomas, N.C.; Bagnato, F. Alemtuzumab for the treatment of multiple sclerosis. Expert Opin. Biol. Ther. 2018, 18, 323–334. [Google Scholar] [CrossRef]
- Ruck, T.; Bittner, S.; Wiendl, H.; Meuth, S.G. Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond. Int. J. Mol. Sci. 2015, 16, 16414–16439. [Google Scholar] [CrossRef] [PubMed]
- Agius, M.A.; Klodowska-Duda, G.; Maciejowski, M.; Potemkowski, A.; Eliezer, K.; Patra, K.; Wesley, J.; Madani, S.; Barron, G.; Katz, E.; et al. Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study. Mult. Scler. J. 2019, 25, 235–245. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frampton, J.E. Inebilizumab: First Approval. Drugs 2020, 80, 1259–1264. [Google Scholar] [CrossRef]
- Edwards, J.C.; Szczepanski, L.; Szechinski, J.; Filipowicz-Sosnowska, A. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 2004, 350, 2572–2581. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- He, D.; Guo, R.; Zhang, F.; Zhang, C.; Dong, S.; Zhou, H. Rituximab for relapsing-remitting multiple sclerosis. Cochrane Database Syst. Rev. 2013, 2013, CD009130. [Google Scholar] [CrossRef]
- McGinley, M.P.; Moss, B.; Cohen, J.A. Safety of monoclonal antibodies for the treatment of multiple sclerosis. Expert Opin. Drug Saf. 2017, 16, 89–100. [Google Scholar] [CrossRef] [PubMed]
- Teng, Y.K.O.; Bruce, I.N.; Diamond, B.; Furie, R.A.; Van Vollenhoven, R.F.; Gordon, D.; Groark, J.; Henderson, R.B.; Oldham, M.; Tak, P.P. Phase III, multicentre, randomised, double-blind, placebo-controlled, 104-week study of subcutaneous belimumab administered in combination with rituximab in adults with systemic lupus erythematosus (SLE): BLISS-BELIEVE study protocol. BMJ Open 2019, 9, e025687. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cambridge, G.; Leandro, M.J.; Teodorescu, M.; Manson, J.; Rahman, A.; Isenberg, D.; Edwards, J.C. B cell depletion therapy in systemic lupus erythematosus: Effect on autoantibody and antimicrobial antibody profiles. Arthritis Rheum. 2006, 54, 3612–3622. [Google Scholar] [CrossRef]
- Pescovitz, M.D.; Torgerson, T.R.; Ochs, H.D.; Ocheltree, E.; McGee, P.; Krause-Steinrauf, H.; Lachin, J.; Canniff, J.; Greenbaum, C.; Herold, K.C.; et al. Effect of rituximab on human in vivo antibody immune responses. J. Allergy Clin. Immunol. 2011, 128, 1295–1302.e5. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Roberts, D.M.; Jones, R.; Smith, R.M.; Alberici, F.; Kumaratne, D.S.; Burns, S.; Jayne, D.R. Rituximab-associated hypogammaglobulinemia: Incidence, predictors and outcomes in patients with multi-system autoimmune disease. J. Autoimmun. 2015, 57, 60–65. [Google Scholar] [CrossRef]
- Eming, D.; Nagel, A.; Wolff-Franke, S.; Podstawa, E. Rituximab Exerts a Dual Effect in Pemphigus Vulgaris. J. Investig. Dermatol. 2008, 128, 2850–2858. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stasi, R.; Del Poeta, G.; Stipa, E.; Evangelista, M.L.; Trawinska, M.M.; Cooper, N.; Amadori, S. Response to B-cell–depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura. Blood 2007, 110, 2924–2930. [Google Scholar] [CrossRef] [PubMed]
- Hoch, W.; McConville, J.; Helms, S.; Newsom-Davis, J.; Melms, A.; Vincent, A. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat. Med. 2001, 7, 365–368. [Google Scholar] [CrossRef]
- Sangwook, O.; Kevin, O.C.; Aimee, P. MuSK Chimeric Autoantibody Receptor (CAAR) T Cells for Antigen-specific Cellular Immunotherapy of Myasthenia Gravis (2769). Neurology 2020, 94, 2769. [Google Scholar]
- Ellebrecht, C.T.; Bhoj, V.G.; Nace, A.; Choi, E.J.; Mao, X.; Cho, M.J.; Di Zenzo, G.; Lanzavecchia, A.; Seykora, J.T.; Cotsarelis, G.; et al. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science 2016, 353, 179–184. [Google Scholar] [CrossRef] [Green Version]
- Bollmann, F.M. Rheumatic autoimmune diseases: Proposed elimination of autoreactive B-cells with magnetic nanoparticle-linked antigens. Med. Hypotheses 2012, 78, 479–481. [Google Scholar] [CrossRef]
- Imura, Y.; Ando, M.; Kondo, T.; Ito, M.; Yoshimura, A. CD19-targeted CAR regulatory T cells suppress B cell pathology without GvHD. JCI Insight 2020, 5, e136185. [Google Scholar] [CrossRef]
- Townsend, M.; Monroe, J.G.; Chan, A.C. B-cell targeted therapies in human autoimmune diseases: An updated perspective. Immunol. Rev. 2010, 237, 264–283. [Google Scholar] [CrossRef]
- Vincent, F.B.; Morand, E.F.; Mackay, F. BAFF and innate immunity: New therapeutic targets for systemic lupus erythematosus. Immunol. Cell Biol. 2012, 90, 293–303. [Google Scholar] [CrossRef]
- Musette, P.; Bouaziz, J.D. B Cell Modulation Strategies in Autoimmune Diseases: New Concepts. Front. Immunol. 2018, 9, 622. [Google Scholar] [CrossRef] [PubMed]
- Jagessar, S.A.; Heijmans, N.; Bauer, J.; Blezer, E.; Laman, J.D.; Migone, T.-S.; Devalaraja, M.N.; Hart, B.A. T Antibodies Against Human BLyS and APRIL Attenuate EAE Development in Marmoset Monkeys. J. Neuroimmune Pharmacol. 2012, 7, 557–570. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mackay, F.; Schneider, P. Cracking the BAFF code. Nat. Rev. Immunol. 2009, 9, 491–502. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Furie, R.; Rovin, B.H.; Houssiau, F.; Malvar, A.; Teng, Y.O.; Contreras, G.; Amoura, Z.; Yu, X.; Mok, C.-C.; Santiago, M.B.; et al. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N. Engl. J. Med. 2020, 383, 1117–1128. [Google Scholar] [CrossRef] [PubMed]
- Kaegi, C.; Steiner, U.C.; Wuest, B.; Crowley, C.; Boyman, O. Systematic Review of Safety and Efficacy of Atacicept in Treating Immune-Mediated Disorders. Front. Immunol. 2020, 11, 433. [Google Scholar] [CrossRef]
- Kalled, S.L.; Cutler, A.H.; Ferrant, J.L. Long-term anti-CD154 dosing in nephritic mice is required to maintain survival and inhibit mediators of renal fibrosis. Lupus 2001, 10, 9–22. [Google Scholar] [CrossRef]
- Wang, X.; Huang, W.; Schiffer, L.E.; Mihara, M.; Akkerman, A.; Hiromatsu, K.; Davidson, A. Effects of anti-CD154 treatment on B cells in murine systemic lupus erythematosus. Arthritis Rheum. 2003, 48, 495–506. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Chen, F.; Putt, M.; Koo, Y.K.; Madaio, M.; Cambier, J.C.; Cohen, P.L.; Eisenberg, R.A. B Cell Depletion with Anti-CD79 mAbs Ameliorates Autoimmune Disease in MRL/lpr Mice1. J. Immunol. 2008, 181, 2961–2972. [Google Scholar] [CrossRef] [Green Version]
- Honigberg, L.A.; Smith, A.M.; Sirisawad, M.; Verner, E.; Loury, D.; Chang, B.; Li, S.; Pan, Z.; Thamm, D.; Miller, R.A.; et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc. Natl. Acad. Sci. USA 2010, 107, 13075–13080. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gatumu, M.; Skarstein, K.; Papandile, A.; Browning, J.L.; Fava, R.A.; Bolstad, A.I. Blockade of lymphotoxin-beta receptor signaling reduces aspects of Sjögren syndrome in salivary glands of non-obese diabetic mice. Arthritis Res. Ther. 2009, 11, R24. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Wolff, A.S.B.; Braun, S.; Husebye, E.S.; Oftedal, B.E. B Cells and Autoantibodies in AIRE Deficiency. Biomedicines 2021, 9, 1274. https://doi.org/10.3390/biomedicines9091274
Wolff ASB, Braun S, Husebye ES, Oftedal BE. B Cells and Autoantibodies in AIRE Deficiency. Biomedicines. 2021; 9(9):1274. https://doi.org/10.3390/biomedicines9091274
Chicago/Turabian StyleWolff, Anette S. B., Sarah Braun, Eystein S. Husebye, and Bergithe E. Oftedal. 2021. "B Cells and Autoantibodies in AIRE Deficiency" Biomedicines 9, no. 9: 1274. https://doi.org/10.3390/biomedicines9091274