Alemtuzumab-Induced Secondary Autoimmune Skin Disorders as Side Effects of Multiple Sclerosis Therapy: Problem That Can Be Influenced or Fate? A Narrative Overview of The Literature A Neuroprotective Role of Vitamin D?
Main Article Content
Abstract
At present, no cure for multiple sclerosis can be made possible with the pharmaceuticals available, nor can a gradual progression of multiple sclerosis be prevented. In the management of multiple sclerosis, it is therefore necessary to determine existing autoimmune diseases through anamnesis before starting alemtuzumab therapy with disease modifying therapy. With previously existing autoimmune diseases or as prophylaxis, comorbidities can be influenced by vitamin D supplementation. Secured pathophysiological and immunological mechanisms of vitamin D on autoimmunological processes support the daily, individually high-dose oral vitamin D intake. This add-on therapy should positively influence the quality of life of persons with multiple sclerosis in the long term. So that the patients do not reject the highly efficient multiple sclerosis therapy for fear of side effects, this therapy offer is a way of avoiding side effects of alemtuzumab administration, such as alopecia, vitiligo, and thyroid diseases, and of decisively influencing the course of MS. This increases the compliance of the persons with multiple sclerosis in therapy. The pathophysiological mechanisms of alopecia and vitiligo are shown. The immunological mechanisms of vitamin D and its influence on autoimmune diseases are described. The previous use of vitamin D in the therapy of these skin diseases is presented and oral supplementation is put up for discussion. The additional neuroprotective effect is evident. Preventing infection with oral vitamin D supplements, particularly in coronavirus disease 2019, may prevent or mitigate multiple sclerosis exacerbations.
Keywords:
Multiple sclerosis, alemtuzumab, autoimmune adverse effects, alopecia, vitiligo, vitamin D supplementation, SARS-CoV-2 infection, neuroprotection
Article Details
How to Cite
GOISCHKE, Hans-Klaus.
Alemtuzumab-Induced Secondary Autoimmune Skin Disorders as Side Effects of Multiple Sclerosis Therapy: Problem That Can Be Influenced or Fate? A Narrative Overview of The Literature A Neuroprotective Role of Vitamin D?.
Medical Research Archives, [S.l.], v. 10, n. 12, dec. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3503>. Date accessed: 16 apr. 2024.
doi: https://doi.org/10.18103/mra.v10i12.3503.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Wiendl H, Gold R, Berger T, et al. Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper). Ther Adv Neurol Disord. 2021;14:1-39
2. Ruck T, Barman S, Schulte-Mecklenbeck A, et al. Aemtuzumab-induced immune phenotype and repertoire changes: implications for secondary autoimmunity. Brain. 2022;145(5):1711-1725
3. Alcalá C, Pzére-Miralles F, Gascón F, et al. Recurrent and universal alopecia areata following alemtuzumab treatment in multiple sclerosis: A secondary autoimmune disease. Mult Scler. 2019;27;406-408
4. Dikeoulia E, Neufeld M, Pawlitzki M, Böhm M. Alemtuzumab-induced Alopecia areata-a case report and systematic literature review of adverse events associated with alemtuzumab. JDDG. 2021;19(8):1159-1164
5. Porwal MH, Salter A, Patel D, Obeidat AZ. Alopecia in Multiple Sclerosis patients treated with Disease Modifying Therapies. J Cent Nerv Syst Diseas. 2022;14:1-10
6. Chan JK, Traboulsee AL, Sayao A-L. Case of alemtuzumab-related alopecia areata management in MS. Neurol Neuroimmunol Neuroinflamm. 2019:6(1):e516
7. Rajabi F, Abdullahimajd F, Jabalameli N, Nasiri Kashani M. Firooz A. Immunogenetics of Alopecia Areata. Adv in Exp Med Biol. 2022,1367:19-59,
8. Colucci R, Conti R, Dragoni F et al. Evidence of a possible therapeutic role of vitamin D in a cohort of adult Caucasian vitiligo patients. Int J Vitam Nutr Res. 2020; 90(3-4):200-204
9. Siddappa H, Kumar YHK, Vivekananda N. Evaluation of Association of Vitamin D in Alopecia Areata: A Case-control Study of 100 patients in a Tertiary Rural Hospital of Southern India. Indian Dermatol Online J. 2019:10(1):45-49
10. Oh J, Saidha S, Cortese I, et al. Daclizumab-induced adverse events in multiple organ systems in multiple sclerosis. Neurology. 2014;18;82(11):984-988
11. Chin LD, AbuHilal M, Ocrelizumab-induced alopecia areata-A series of five patients from Ontario, Canada: A case report. SAGE Open Med Case Rep. 2020; 8:2050313X20919614
12. Simakou T, Butcher JP, Reid St, Henriquez FL. Alopecia areata- Multifactor autoimmune disease, J Autoimmun. 2019:98, 74-85
13. Rossi A, Muscianese M, Federico A et al. Associations between alopecia areata and multiple sclerosis: A report of two cases and review of the literature. Int J Dermatol. 2020;59(4):490-493
14. Ruiz RL, Fernàndez, Ruiz de Arcos M, et al. Skin autoimmunity Secondary to Alemtuzumab in a Tertiary Care Spanish Hospital. Neurology Clin Prac. 2022;12(1):29-35
15. Bliddal S, Nielsen CH, Feldt-Rasmussen U. Recent advances in understanding autoimmune thyroid disease: the tallest tree in the forest of polyautoimmunity. F1000Res. 2017:6:1776
16. Gerkowicz A, Chyl-Surdacka K, Krasowska D, Chodorowska G. The Role of Vitamin D in Non-Scarring alopecia. Int J Mol Sci. 2017;18(12):2653
17. Papadimitriou DT, Bothou Ch, Dermitzake E, Alexopoulos A, Masstorakos G. Treatment of alopecia totalis/universalis/focalis with vitamin D and analogs: Three case reports and a literature review. World J Clin Pediatr. 2021;10(6):192-199
18. da Costa DS, Hygino J, Ferreira TB, et al. Vitamin D modulates different IL-17-secreting T cell subsets in multiple sclerosis patients. J Neuroimmunol. 2016; 299:8-18
19. Tsai, TY, Huang Y-C. Vitamin D deficiency in patients with alopecia areata: a systematic review and meta-analysis. J Am Acad Dermatol. 2018;78(1):207-209
20. Lin X, Meng X, Song Z. Vitamin D and alopecia areata: possible roles in pathogenesis and potential implications for therapy. Am J Transl Res. 2019;11(9):5285-5300
21. Lee S, Kim BJ, Lee CH, Lee WS. Increased prevalence of vitamin D deficiency in patients with alopecia areata: a systematic review and meta-analyses. J Eur Acad Dermatol Venerol. 2018;32(7):1214-21
22. Daroach M, Narang T, Saikia UN, Sachdeva N, Kumaran MS. Correlation of vitamin D and vit D receptor expression in patients with alopecia areata: a clinical paradigm. Int J Dermatol. 2018;57(2):217-222
23. Bizzaro G, Antico A, Fortunato A, Bizzaro N. Vitamin D and Autoimmune Diseases: Is Vitamin D Receptor (VDR) Polymorphism the Culprit. Isr Med Assoc. 2017:19(7):438-443
24. Galoppin M, Kari S, Doldati S, et al. Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications. Brain. 2022;4(4), fcac171.
25. Pierrot-Deseilligny Ch, Souberbielle J-C. Vitamin D and multiple sclerosis: An update. Mult Scler Rel Disord. 2017; 14:35-45
26. Harrison StR, Li D, Jeffery LE, Raza K, Hewison M. Vitamin D, autoimmune Disease and Rheumatoid Arthritis. Calcif Tissue Int. 2020;106(1):58-75
27. Unal M, Gonulalan G. Serum vitamin D level is related to disease severity in pediatric alopecia areata. J Cosmet Dermatol. 2018:17(1):101-104
28. Gao Y, Huo S; Sun M, et al. Evaluation of several immune and inflammatory indicators and their association with alopecia areata. J Cosmet Dermatol. 2022;7,2995-3001
29. Conic RRZ, Piliang M, Bergfeld W, Atanaskova-Mesinkovska N. Vitamin D status in scarring and nonscarring alopecia. Am Acad Dermatol. 2021;85(2): 478-480
30. Lizarondo FPF, Gervasio MKR, Chamberlin ChVS, Gnilo CMS, Silva CY. Determination of serum 25-hydroxyvitamin D levels in patients with alopecia areata and their comparison with levels in healthy controls: a cross-sectional study. JAAD International. 2021;5:78-84
31. Cerman AA, Solak SS, Altunay L, Kücükünal NA. Topical Calcipotriol Therapy for Mild-to-Moderate Alopecia Areata: A Retrospective Study. J Drugs Dermatol. 2015;14(6):616-20
32. Molinelli E, Campanati A, Brisigotti V, Sapigni C, Paolinelli M. Offidani A. Efficacy and Safety of Topical Calcipotriol 0.005% Versus Topical clobetasol 0.05% in the Management of Alopecia Areata: An Intrasubject Pilot Study. Dermatol Ther. (Heidelb.). 2020;10(3): 515-521
33. Narang T, Daroach M, Kumaran MS. Efficacy and safety of topical calcipotriol in management of alopecia areata: A pilot study. Dermatol Ther. 2017;30(3): e122464
34. Afvari S, Kazlouskaya M, Cline A. Reply to “Vitamin D status in scarring and nonscarring alopecia”. JAAD online, 2022;87(2): E89-E90
35. Sattar F, Almas U, Ibrahim NA, Akhtar A, Shazad MK, Akram S et al. Efficacy of oral Vitmain D3 Therapy in Patients suffering from Diffuse Hair Loss (Telogen Effluvium). J Nutr Sci Vitaminol. 2021;67:68-71
36. Harvey C. Combined Diet and Supplementation Therapy Resolves Alopecia Areata in a Paediatric patient: A Case Study. Cureus. 2020;12(11):e11371
37. Boriello G, Ianiello A, Toosy AT. Alopecia Universalis Occuring after Alemtuzumab Treatment for Multiple Sclerosis. A Two-Year Follow-Up of Two Patients. Int J Environ Res Public Health. 2021;18(14):7338
38. Varikasuvu SR, Aloori S, Varshney, S, Bhonir AV. Decreased circulatory levels of vitamin D in vitiligo: a meta-analysis. A Bras Dermatol. 2021;96(3):284-294.
39. Tuchinda P, Kulthanan K, Chularojanamontri L et al. Relationship between vitamin D and chronic spontaneous urticaria. A systematic review. Clin Transl Allergy. 2018;8:51
40. Amer A, Amer M, Khater EMG, Marei A M, Firjani BAA. Correlation between Vitamin D and Interleukin-21 in Patients with Vitiligo. J Clin Dermatol Ther. 2019;5:039 Doi.10.24966/CDT-8771/100039.
41. Aly D, Mohammed F. Sayed K, Gawdat H, Mashaly H, Hay RA et al. Is there a Relation between Vitamin d and Interleukin-17 in Vitiligo? A Cross-Sectional Study. Dermatology. 2017;233(6):413-418
42. Dubuis ML, Pagano MT, Pierdominici M, Ortona E. The role of vitamin D in autoimmune diseases: could sex make the difference? Biol Sex Differ. 2021:12:12
43. Hayes CE, Hubler SL, Moore JR, Barta LE, Praska CE, Nashold FE. Vitamin D Actions on CD4(+) T Cells in autoimmune disease. Front Immunol. 2015;6:100
44. Bhargava P, Sotirchos E, Eckstein Ch, et al. High-dose vitamin D supplementation reduces IL-17 producing CD4+ T –cells and effector-memory CD4+ T-cells in multiple sclerosis patients (S38.001). Neurology. 2015:84 (14 Suppl.)
45. Charoenngam N, Holick MF. Immunologic Effects of Vitamin D on Human health and Disease. Nutrients. 2020;12(7):2097
46. Martens PJ, Gysemans C, Verstuyf A, Methieu AC. Vitamin D’s Effect an immune function. Nutrients. 2020;12(5):1248.
47. Bishop EL, Ismailova A, Dimeloe S, Hewison M, White JH. Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti-Inflammatory. NBMR Plus. 2020;5(1):e10405
48. Hahn, J, Cook NR, Alexander EK, et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized control trial. BMJ. 2022:376e066452
49. Ren HM, Lukacher AE, Rahman ZSM, Olsen NJ. New developments implicating IL-21 in autoimmune disease. J Autoimmun. 2021;122:102689
50. Ruck T, Pfeuffer S, Schulte Mecklenbeck A, et al. Vitiligo after alemtuzumab treatment: Secondary autoimmunity is not all about B cells. Neurology. 2018;91(24):e2233-e2237
51. Jefferey LE, Burke F, Mura M, Zheng Y, et al. 1,25-dihydroxyvitamin D3 and interleukin-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol 2009;183(9):5458-5467
52. Feng Y, Qiu T, Chen H, et al. Association of serum IL-21 and vitamin D concentrations in Chinese children with autoimmune thyroid disease. Clin Chim Acta. 2020;507:194-198.
53. O’Conell K, SulaimaniJ, Basdea SA, et al. Effects of vitamin D3 in clinically isolated syndrome and healthy control participants: a double-blind randomized controlled trial. Mult Scler J Exp Trans Clin. 2017;3(3):2055217317727296.
54. Bhargava P, Steele SU, Waubant E, et al. Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls. Mult Scler. 2016;22(6):753-760
55. Agnello L, Scazzone C, Sasso BL, et al. Role of Multiple Vitamin D-Related Polymorphisms in Multiple Sclerosis Severity: Preliminary Findings. Genes. 2022;13,1307
56. Malhotra S, Midaglia L, Chuquisana O, et al. The CYP24A1 Gene Variant rs2762943 is Associated with low Serum 1,25-DihydroxyvitaminD levels in Multiple Sclerosis Patients. J Neuroinflamm. 2021, Posted Date Dec 17th 2021.
57. Mimpen M, Rolf L, Poelmans G, et al. Vitamin D related genetic polymorphisms affect serological response to high-dose vitamin D supplementation in multiple sclerosis. PLoS One. 2021;2;16(12): e0261097
58. Goischke H-K. AlemtuzumabTreatment-Induced Thyroid Dysfunction in RRMS: a Varied Clinical Picture in an Interdisciplinary Terrain. Akt Neurol. 2017;44:1-8
59. Goischke H.K. Vitamin D supplementation for the prevention or depletion of side effects of therapy with alemtuzumab in multiple sclerosis. Therapeutic Clin Risk Man. 2019;15:891-904
60. Rauma I, Mustonen T, Sepp Ä JM, et al. Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients. J Neurol. 2022;269(2):824-853
61. Rotondi M, Molteni M, Leporati P, Capelli V, Marino M, Chiovato L. Autoimmune Thyroid diseases in Patients Treated with Alemtuzumab for Multiple Sclerosis: An Example of Selective Anti-TSH receptor Immune Response. Front Endocrinol (Lausanne) 2017;8:254
62. Vandebergh M, Dubois B, Goris A. Effects of Vitamin D and body Mass Index on Disease Risk and Relapse Hazard in Multiple Sclerosis: A Mendelian Randomization Study. Neurol Neuroimmunol Neuroinflamm. 2022;9(3)e1165
63. Miclea A, Bagnoud M, Chan A, Hoepner. A Brief Review of the Effects of Vitamin D on Multiple Sclerosis. Front Immuno. 2020;11:781.
64. Sintzel M. Rametta M, Redler AT. Vitamin D and Multiple Sclerosis: A Comprehensive Review. Neurol Ther 2018;7(1):59-85
65. Lemke D, Klement RJ, Schweiger F, Schweiger B, Spitz J. Vitamin D resistance as a possible Causa of Autoimmune disease: A Hypothesis confirmed by a therapeutic high-dose vitamin D protocol. Front Immunol. 2021;7,12, 655739
66. Finamor DC, Sinigaglia-Coimbra R, Neves LC, et al. A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriases. Dermatoendocrinol. 2013;5:222-34
67. Giovannoni G, Popescu V, Wuerfel J, et al. Smouldering multiple sclerosis: the ‘real MS’. Ther Adv Neurol Disord. 2022;15,1-8
68. Alvarez JI, Cayrol R, Prat A. Disruption of central nervous system barriers in multiple sclerosis. Biochim Biophys Acta. 2011;1812:252–264
69. Mapunda JA, Tibar H, Regragiu W, Engelhardt B. How Does the Immune System Enter the Brain? Front Immunol. 2022;13:805657
70. Takahashi S, Maeda T, Sano Y, Nishihara H, Takeshita Y, Shimizu F et al. Active form of vitamin D directly protects the blood-brain barrier in multiple sclerosis. Clin Exp Neuroimmunol. 2017;8(3):244-254. Doi.org/101111/cen3.12398
71. Nishihara H, Engelhardt B. Brain Barriers, and Multiple Sclerosis: Novel Treatment Approaches from a Brain Barriers Perspective. Handb Exp Pharmacol. 2022:273:295-329
72. De Oliveira et al. Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation. Front Pharmacol 2020;11:161. Doi. 10.3389/fphar.2020.00161
73. Grishkan IV, Fairchild AN, Calabresi PA and Gocke AR. 1,25-Dihydroxyvitamin D3 selectively and reversibly impairs T helper-cell CNS localization. PNAS. 2013;110(52):21 101-21 106. Doi.org/10.1073/pnas.1306072110
74. Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA 1996;93(15):7861-4 doi: 10.1073/pnas.93.15.7861.
75. Hollis BW, Wagner CL. The Role of the Parent Compound Vitamin D with Respect to Metabolism and Function: Why Clinical Dose Intervals Can Affect Clinical Outcomes. J Clin Endocrinol Metab. 2013;98(12):4619-28 Doi.org/10.1210/jc.2013-2653
76. Gombash SE, Lee PW, Sawdai E, Lovett-Racke EE. Vitamin D as a Risk Factor for Multiple Sclerosis: Immunoregulatory or Neuroprotective? Front Neurol. 2022;13:796933
77. Mayne PE, Burne THJ. Vitamin D in Synaptic Plasticity, Cognitive Function, and Neuropsychiatric Illness. Trends Neurosci. 2019;42(4).293-306
78. Holick MF. Vitamin D and brain health: the need for vitamin D supplementation and sensible sun exposure. J Intern Med. 2015;277(1)90-3
79. Eyles DW. Vitamin D: Brain and Behavior. JBMR Plus. 2020;5(1)/e10419
80. AlJohri R, AIOkai M, Haq SH. Neuroprotective role of vitamin D in primary neuronal cortical culture. Neurological Sci. 2019;14:43-48, doi. 10.1016/j.ensci.2018.12.004
81. Zorzella-Pezavento SFG, Mimura LAN, Denadai MB et al. Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis? Neurol. Regeneration Research. 2022;17(9):1945-1954, DOI: 10.4103/1673-5374.335139
82. Boltjes R, Knippenberg S, Gerlach O, Hupperts R, Damoiseaux J. Vitamin D supplementation in multiple sclerosis: An expert opinion based on the review of current evidence. Expert Rev Neurother. 2021;21(6):715-725
83. Smolders J, Torkildsen O, Camu W, Holmoy T. An Update on vitamin D and disease Activity in Multiple Sclerosis. CNS Drugs. 2019;33(12):1187-1199
84. García Menéndez S, Giménez VMM, Holick MF, Barrantes FJ, and Manucha W. COVID-19 and neurological sequelae: Vitamin D as a possible neuroprotective and/or neuroreparative agent. Life Sci. 2022 May 15; 297: 120464.Published online 2022 Mar 7. doi: 10.1016/j.lfs.2022.120464
85. Xu Y, Baylink DJ, Chen CH-S, et al. The importance of vitamin D metabolism as a potential prophylactic, immunregulatory and neutroprotective treatment for COVID-19. J Transl Med 2020;18:322
86. Abbatemarco JR, Fox RJ, Li H, and Ontaneda D. Vitamin D and MRI Measures in Progressive Multiple Sclerosis. Mult Scler Relat Disord. 2019; 35: 276–282. Doi.10.1016/j.msard.2019.08.014
87. Longinetti E, Bower H, McKay KA, Englund S, Burman J, Fink K et al. COVID-19 clinical outcomes and DMT of MS patients and population-based controls. ACTN 2022, First publ. 22 August
88. Cauchi M, Willis M, Adrews A, et al. Multiple sclerosis, and the risk of infection: association of British Neurologists consensus guideline. Pract Neurol. 2022
89. Ballering AV, van Zon SKR, Hartman TC, Rosmalen J GM et al. Persistence of somatic symptoms after COVID-19 in the Netherland. an observational cohort studies. Lancet. 2022;400:452-61
90. Gerhard A, Prüß H, Franke C. Manifestations of the central nervous system after COVID-19. Nervenarzt. 2022;93:769-778
91. Orry B, Szekeres-Bartho J, Bizzarri M, Spiga AM, Unfer V. Inhibitory effects of Vitamin D on inflammation and IL-6 release. A further support for COVID-19. Eur Rev Med Pharmacol Sci. 2020;24:8187-8193
92. Silberstein M. COVID-19 and IL-6: Why vitamin D (probably) helps but tocilizumab might not. Eur J Pharmacol. 2021;899:174031
93. Campi I, Gennari L, Merlotti D, et al. Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy. BMC Infectious Diseases. 2021;21:566
94. Malaguanera L. Vitamin D3 as potential treatment adjuncts for CORONA-19. Nutrients. 2020; 12(11) 3512
95. Gönen MS, Alaylioglu M, Durcan E, et al. Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-COV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1. Nutrients. 2021;13(11):4044
96. Garjani A, Middleton RM, Nicholas R, Evangelou N. Recovery From COVID-19 in Multiple Sclerosis. Neurology: Neuroimmunology and Neuroinflammation 2022;9,e1118
97. Glinsky, G. Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells. Biomedicines. 2020; 8(5):129
98. Chiodini I, Gatti D, Soranna D, Merlotti D, Mingiano Ch, Fassio A et al. Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes. Front Public Health. 2021;9:736665
99. Petrelli F, Luciani A, Perego G, et al. Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analyses of 43 observational studies. J Steroid Biochem Mol Biol. 2021;211:105883
100. Fiorino S, Zippi M, Gallo C, et al. The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities. Br J Nutr. 2020; online 24 July 2020
101. Peng M-Y, Liu W-Ch, Zheng J-Q, et al. Immunological Aspects of SASRS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D. Int J Mol Sci. 2021;22(10):5251
102. Chiu SK. Putative Role of Vitamin D for COVID-19 Vaccination. Int Sci. J Mol. 2021:22(16):8988
103. Goncalves-Mendes N, Talvas J, Dualè C, et al. Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons. Front Immunol. 08 Febr 2019
104. Chillon TS, Demircan K, Heller RA, et al. Relationship between Vitamin D Status and Antibody Response to COVID-19 mRNA Vaccination in Healthy Adults. Biomedicines,18 Nov. 2021
105. Grant WB, Lahore H, McDonell SL, et al. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Death. Nutrients. 2020;12(4):988
106. Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment, and prevention. Rev Endocr Metab Disord. 2017;18:153-65
107. Dobson R, Cock HR, Brex P, Giovannoni G. Vitamin D supplementation. Pract. Neurol. 2018;18:35-42
108. Wimalawansa S. Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections-Sepsis and COVID-19. Nutrients. 2022;14(14):2997
109. Bae JH, Choe HJ, Holick MF. Lim S. Association of vitamin D status with COVID-19 and its severity: Vitamin D and COVID-19: a narrative review. Rev Endocrine Disord 2022;23(3):579-599
110. Martineau AR, Jolliffe DA, Greenberg L, et al. Vitamin D supplementation to prevent acute respiratory tract infections: individual participant data meta-analysis. Health Technol Assess. 2019;23(2):1-44
111. Helde-Frankling M, Björkhem-Bergman L. Vitamin D in Pain Management. Int J Mol Sci. 2017;18:2170.
112. Hollis BW, Wagner CL, The Role of the Parent Compound Vitamin D with Respect to Metabolism and Function. Why Clinical Dose Intervals Can Affect Clinical Outcomes. J Clin Endocrinol Metab. 2013;98:4619-4628
113. Feige J, Moser T, Bieler L. Schwenker K, Hauer L Sellner J. Vitamin d Suoolementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats. Nutrients. 2020;12(3):783
114. Calton EK, Keane KN, Newsholme P, Soares MJ. The impact of Vitamin D levels on Inflammatory Status: A systematic Review of Immune Cell Studies. PLoS One 2015;10(11):e0141770
115. Shoemaker TJ, Mowry EM. A review of vitamin D supplementation as disease-modifying therapy. Mult Scler. 2018;24(1).6-11
116. Wesnes K, Myhr K-M, Riise T, Kvistad SS, Torkildsen O, Wergeland S et al. Low vitamin D, but not tobacco use or high BMI, is associated with long-term disability progression in multiple sclerosis. Mult Scler Relat Disord. 2021;50:102801
117. Jetty V; Lueck CJ, Wang P, et al. Safety of 50,000-100,000 Units of Vitamin D3/Week in vitamin D-Deficient, Hypercholesterolemic patients with reversible Statin Intolerance. N Am J Med Sci. 2016;8(3):156-162
118. Sotirchhos ES, Bhargave P, Eckstein C, Van Haren K, Baynes M, Nitranos A. Safety, and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. Neurology. 2016;86(4):382-390
119. Häusler D, Torke S, Peelen E, Bertsch T, Djukic M, Nau R et al. High dose vitamin D exacerbation central nervous system autoimmunity by raising T cell excitatory calcium. Brain. 2019;142:2737-55
120. Carlberg C, Haq A. The concept of the personal vitamin D response index. J Steroid Biochem Mol Biol. J 2018;175,12-17
121. Mapunda JA, Tibar H, Regragui W, Engelhardt B. How Does the Immune System Enter the Brain? Front Immunol. 2022;13:805657
122. Engelhardt B, Comabella M, Chan A. Multiple sclerosis: Immunopathological heterogeneity and its implications. Eur J Immunol. 2022;52(6):869-881
123. Kuhlmann J. et al. Multiple sclerosis progression: time for a new mechanism – driven framework. Lancet Neurol 2022, publ. online. 18.Nov.2022
124. Cagol A et al. Association of brain atrophy with disease progression independent of relapse activity in patients with relapsing multiple sclerosis. JAMA Neurology 2022;79(7):682-692
125. Absinta M et al. Association of chronic active multiple sclerosis lesions with disability in vivo. JAMA Neurol 2019;76(12):1474-1483.
126. Spanier JA et al. Vitamin D3-mediated resistance to a multiple sclerosis model disease depends on myeloid cell 1,15-dihydroxyvitamin D3 synthesis and correlates with increased CD4+ T cell CTLA-4 expression. J Neuroimmunology 2019:338:577105
127. Radandish M et al. The role of distinct subsets of macrophages in the pathogenesis of MS and the impact of different therapeutic agents on these population. Front Immunol 2021;12:667705
128. Wang J et al. Targeting microglia and macrophages: A potential treatment strategy for multiple sclerosis. Front Pharmacol 2019;10:286
129. Lee, PW et al. Neuron-specific vitamin d signaling attenuates microglia activation and CNS autoimmunity. Front Neurol 2020;11:19
2. Ruck T, Barman S, Schulte-Mecklenbeck A, et al. Aemtuzumab-induced immune phenotype and repertoire changes: implications for secondary autoimmunity. Brain. 2022;145(5):1711-1725
3. Alcalá C, Pzére-Miralles F, Gascón F, et al. Recurrent and universal alopecia areata following alemtuzumab treatment in multiple sclerosis: A secondary autoimmune disease. Mult Scler. 2019;27;406-408
4. Dikeoulia E, Neufeld M, Pawlitzki M, Böhm M. Alemtuzumab-induced Alopecia areata-a case report and systematic literature review of adverse events associated with alemtuzumab. JDDG. 2021;19(8):1159-1164
5. Porwal MH, Salter A, Patel D, Obeidat AZ. Alopecia in Multiple Sclerosis patients treated with Disease Modifying Therapies. J Cent Nerv Syst Diseas. 2022;14:1-10
6. Chan JK, Traboulsee AL, Sayao A-L. Case of alemtuzumab-related alopecia areata management in MS. Neurol Neuroimmunol Neuroinflamm. 2019:6(1):e516
7. Rajabi F, Abdullahimajd F, Jabalameli N, Nasiri Kashani M. Firooz A. Immunogenetics of Alopecia Areata. Adv in Exp Med Biol. 2022,1367:19-59,
8. Colucci R, Conti R, Dragoni F et al. Evidence of a possible therapeutic role of vitamin D in a cohort of adult Caucasian vitiligo patients. Int J Vitam Nutr Res. 2020; 90(3-4):200-204
9. Siddappa H, Kumar YHK, Vivekananda N. Evaluation of Association of Vitamin D in Alopecia Areata: A Case-control Study of 100 patients in a Tertiary Rural Hospital of Southern India. Indian Dermatol Online J. 2019:10(1):45-49
10. Oh J, Saidha S, Cortese I, et al. Daclizumab-induced adverse events in multiple organ systems in multiple sclerosis. Neurology. 2014;18;82(11):984-988
11. Chin LD, AbuHilal M, Ocrelizumab-induced alopecia areata-A series of five patients from Ontario, Canada: A case report. SAGE Open Med Case Rep. 2020; 8:2050313X20919614
12. Simakou T, Butcher JP, Reid St, Henriquez FL. Alopecia areata- Multifactor autoimmune disease, J Autoimmun. 2019:98, 74-85
13. Rossi A, Muscianese M, Federico A et al. Associations between alopecia areata and multiple sclerosis: A report of two cases and review of the literature. Int J Dermatol. 2020;59(4):490-493
14. Ruiz RL, Fernàndez, Ruiz de Arcos M, et al. Skin autoimmunity Secondary to Alemtuzumab in a Tertiary Care Spanish Hospital. Neurology Clin Prac. 2022;12(1):29-35
15. Bliddal S, Nielsen CH, Feldt-Rasmussen U. Recent advances in understanding autoimmune thyroid disease: the tallest tree in the forest of polyautoimmunity. F1000Res. 2017:6:1776
16. Gerkowicz A, Chyl-Surdacka K, Krasowska D, Chodorowska G. The Role of Vitamin D in Non-Scarring alopecia. Int J Mol Sci. 2017;18(12):2653
17. Papadimitriou DT, Bothou Ch, Dermitzake E, Alexopoulos A, Masstorakos G. Treatment of alopecia totalis/universalis/focalis with vitamin D and analogs: Three case reports and a literature review. World J Clin Pediatr. 2021;10(6):192-199
18. da Costa DS, Hygino J, Ferreira TB, et al. Vitamin D modulates different IL-17-secreting T cell subsets in multiple sclerosis patients. J Neuroimmunol. 2016; 299:8-18
19. Tsai, TY, Huang Y-C. Vitamin D deficiency in patients with alopecia areata: a systematic review and meta-analysis. J Am Acad Dermatol. 2018;78(1):207-209
20. Lin X, Meng X, Song Z. Vitamin D and alopecia areata: possible roles in pathogenesis and potential implications for therapy. Am J Transl Res. 2019;11(9):5285-5300
21. Lee S, Kim BJ, Lee CH, Lee WS. Increased prevalence of vitamin D deficiency in patients with alopecia areata: a systematic review and meta-analyses. J Eur Acad Dermatol Venerol. 2018;32(7):1214-21
22. Daroach M, Narang T, Saikia UN, Sachdeva N, Kumaran MS. Correlation of vitamin D and vit D receptor expression in patients with alopecia areata: a clinical paradigm. Int J Dermatol. 2018;57(2):217-222
23. Bizzaro G, Antico A, Fortunato A, Bizzaro N. Vitamin D and Autoimmune Diseases: Is Vitamin D Receptor (VDR) Polymorphism the Culprit. Isr Med Assoc. 2017:19(7):438-443
24. Galoppin M, Kari S, Doldati S, et al. Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications. Brain. 2022;4(4), fcac171.
25. Pierrot-Deseilligny Ch, Souberbielle J-C. Vitamin D and multiple sclerosis: An update. Mult Scler Rel Disord. 2017; 14:35-45
26. Harrison StR, Li D, Jeffery LE, Raza K, Hewison M. Vitamin D, autoimmune Disease and Rheumatoid Arthritis. Calcif Tissue Int. 2020;106(1):58-75
27. Unal M, Gonulalan G. Serum vitamin D level is related to disease severity in pediatric alopecia areata. J Cosmet Dermatol. 2018:17(1):101-104
28. Gao Y, Huo S; Sun M, et al. Evaluation of several immune and inflammatory indicators and their association with alopecia areata. J Cosmet Dermatol. 2022;7,2995-3001
29. Conic RRZ, Piliang M, Bergfeld W, Atanaskova-Mesinkovska N. Vitamin D status in scarring and nonscarring alopecia. Am Acad Dermatol. 2021;85(2): 478-480
30. Lizarondo FPF, Gervasio MKR, Chamberlin ChVS, Gnilo CMS, Silva CY. Determination of serum 25-hydroxyvitamin D levels in patients with alopecia areata and their comparison with levels in healthy controls: a cross-sectional study. JAAD International. 2021;5:78-84
31. Cerman AA, Solak SS, Altunay L, Kücükünal NA. Topical Calcipotriol Therapy for Mild-to-Moderate Alopecia Areata: A Retrospective Study. J Drugs Dermatol. 2015;14(6):616-20
32. Molinelli E, Campanati A, Brisigotti V, Sapigni C, Paolinelli M. Offidani A. Efficacy and Safety of Topical Calcipotriol 0.005% Versus Topical clobetasol 0.05% in the Management of Alopecia Areata: An Intrasubject Pilot Study. Dermatol Ther. (Heidelb.). 2020;10(3): 515-521
33. Narang T, Daroach M, Kumaran MS. Efficacy and safety of topical calcipotriol in management of alopecia areata: A pilot study. Dermatol Ther. 2017;30(3): e122464
34. Afvari S, Kazlouskaya M, Cline A. Reply to “Vitamin D status in scarring and nonscarring alopecia”. JAAD online, 2022;87(2): E89-E90
35. Sattar F, Almas U, Ibrahim NA, Akhtar A, Shazad MK, Akram S et al. Efficacy of oral Vitmain D3 Therapy in Patients suffering from Diffuse Hair Loss (Telogen Effluvium). J Nutr Sci Vitaminol. 2021;67:68-71
36. Harvey C. Combined Diet and Supplementation Therapy Resolves Alopecia Areata in a Paediatric patient: A Case Study. Cureus. 2020;12(11):e11371
37. Boriello G, Ianiello A, Toosy AT. Alopecia Universalis Occuring after Alemtuzumab Treatment for Multiple Sclerosis. A Two-Year Follow-Up of Two Patients. Int J Environ Res Public Health. 2021;18(14):7338
38. Varikasuvu SR, Aloori S, Varshney, S, Bhonir AV. Decreased circulatory levels of vitamin D in vitiligo: a meta-analysis. A Bras Dermatol. 2021;96(3):284-294.
39. Tuchinda P, Kulthanan K, Chularojanamontri L et al. Relationship between vitamin D and chronic spontaneous urticaria. A systematic review. Clin Transl Allergy. 2018;8:51
40. Amer A, Amer M, Khater EMG, Marei A M, Firjani BAA. Correlation between Vitamin D and Interleukin-21 in Patients with Vitiligo. J Clin Dermatol Ther. 2019;5:039 Doi.10.24966/CDT-8771/100039.
41. Aly D, Mohammed F. Sayed K, Gawdat H, Mashaly H, Hay RA et al. Is there a Relation between Vitamin d and Interleukin-17 in Vitiligo? A Cross-Sectional Study. Dermatology. 2017;233(6):413-418
42. Dubuis ML, Pagano MT, Pierdominici M, Ortona E. The role of vitamin D in autoimmune diseases: could sex make the difference? Biol Sex Differ. 2021:12:12
43. Hayes CE, Hubler SL, Moore JR, Barta LE, Praska CE, Nashold FE. Vitamin D Actions on CD4(+) T Cells in autoimmune disease. Front Immunol. 2015;6:100
44. Bhargava P, Sotirchos E, Eckstein Ch, et al. High-dose vitamin D supplementation reduces IL-17 producing CD4+ T –cells and effector-memory CD4+ T-cells in multiple sclerosis patients (S38.001). Neurology. 2015:84 (14 Suppl.)
45. Charoenngam N, Holick MF. Immunologic Effects of Vitamin D on Human health and Disease. Nutrients. 2020;12(7):2097
46. Martens PJ, Gysemans C, Verstuyf A, Methieu AC. Vitamin D’s Effect an immune function. Nutrients. 2020;12(5):1248.
47. Bishop EL, Ismailova A, Dimeloe S, Hewison M, White JH. Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti-Inflammatory. NBMR Plus. 2020;5(1):e10405
48. Hahn, J, Cook NR, Alexander EK, et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized control trial. BMJ. 2022:376e066452
49. Ren HM, Lukacher AE, Rahman ZSM, Olsen NJ. New developments implicating IL-21 in autoimmune disease. J Autoimmun. 2021;122:102689
50. Ruck T, Pfeuffer S, Schulte Mecklenbeck A, et al. Vitiligo after alemtuzumab treatment: Secondary autoimmunity is not all about B cells. Neurology. 2018;91(24):e2233-e2237
51. Jefferey LE, Burke F, Mura M, Zheng Y, et al. 1,25-dihydroxyvitamin D3 and interleukin-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol 2009;183(9):5458-5467
52. Feng Y, Qiu T, Chen H, et al. Association of serum IL-21 and vitamin D concentrations in Chinese children with autoimmune thyroid disease. Clin Chim Acta. 2020;507:194-198.
53. O’Conell K, SulaimaniJ, Basdea SA, et al. Effects of vitamin D3 in clinically isolated syndrome and healthy control participants: a double-blind randomized controlled trial. Mult Scler J Exp Trans Clin. 2017;3(3):2055217317727296.
54. Bhargava P, Steele SU, Waubant E, et al. Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls. Mult Scler. 2016;22(6):753-760
55. Agnello L, Scazzone C, Sasso BL, et al. Role of Multiple Vitamin D-Related Polymorphisms in Multiple Sclerosis Severity: Preliminary Findings. Genes. 2022;13,1307
56. Malhotra S, Midaglia L, Chuquisana O, et al. The CYP24A1 Gene Variant rs2762943 is Associated with low Serum 1,25-DihydroxyvitaminD levels in Multiple Sclerosis Patients. J Neuroinflamm. 2021, Posted Date Dec 17th 2021.
57. Mimpen M, Rolf L, Poelmans G, et al. Vitamin D related genetic polymorphisms affect serological response to high-dose vitamin D supplementation in multiple sclerosis. PLoS One. 2021;2;16(12): e0261097
58. Goischke H-K. AlemtuzumabTreatment-Induced Thyroid Dysfunction in RRMS: a Varied Clinical Picture in an Interdisciplinary Terrain. Akt Neurol. 2017;44:1-8
59. Goischke H.K. Vitamin D supplementation for the prevention or depletion of side effects of therapy with alemtuzumab in multiple sclerosis. Therapeutic Clin Risk Man. 2019;15:891-904
60. Rauma I, Mustonen T, Sepp Ä JM, et al. Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients. J Neurol. 2022;269(2):824-853
61. Rotondi M, Molteni M, Leporati P, Capelli V, Marino M, Chiovato L. Autoimmune Thyroid diseases in Patients Treated with Alemtuzumab for Multiple Sclerosis: An Example of Selective Anti-TSH receptor Immune Response. Front Endocrinol (Lausanne) 2017;8:254
62. Vandebergh M, Dubois B, Goris A. Effects of Vitamin D and body Mass Index on Disease Risk and Relapse Hazard in Multiple Sclerosis: A Mendelian Randomization Study. Neurol Neuroimmunol Neuroinflamm. 2022;9(3)e1165
63. Miclea A, Bagnoud M, Chan A, Hoepner. A Brief Review of the Effects of Vitamin D on Multiple Sclerosis. Front Immuno. 2020;11:781.
64. Sintzel M. Rametta M, Redler AT. Vitamin D and Multiple Sclerosis: A Comprehensive Review. Neurol Ther 2018;7(1):59-85
65. Lemke D, Klement RJ, Schweiger F, Schweiger B, Spitz J. Vitamin D resistance as a possible Causa of Autoimmune disease: A Hypothesis confirmed by a therapeutic high-dose vitamin D protocol. Front Immunol. 2021;7,12, 655739
66. Finamor DC, Sinigaglia-Coimbra R, Neves LC, et al. A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriases. Dermatoendocrinol. 2013;5:222-34
67. Giovannoni G, Popescu V, Wuerfel J, et al. Smouldering multiple sclerosis: the ‘real MS’. Ther Adv Neurol Disord. 2022;15,1-8
68. Alvarez JI, Cayrol R, Prat A. Disruption of central nervous system barriers in multiple sclerosis. Biochim Biophys Acta. 2011;1812:252–264
69. Mapunda JA, Tibar H, Regragiu W, Engelhardt B. How Does the Immune System Enter the Brain? Front Immunol. 2022;13:805657
70. Takahashi S, Maeda T, Sano Y, Nishihara H, Takeshita Y, Shimizu F et al. Active form of vitamin D directly protects the blood-brain barrier in multiple sclerosis. Clin Exp Neuroimmunol. 2017;8(3):244-254. Doi.org/101111/cen3.12398
71. Nishihara H, Engelhardt B. Brain Barriers, and Multiple Sclerosis: Novel Treatment Approaches from a Brain Barriers Perspective. Handb Exp Pharmacol. 2022:273:295-329
72. De Oliveira et al. Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation. Front Pharmacol 2020;11:161. Doi. 10.3389/fphar.2020.00161
73. Grishkan IV, Fairchild AN, Calabresi PA and Gocke AR. 1,25-Dihydroxyvitamin D3 selectively and reversibly impairs T helper-cell CNS localization. PNAS. 2013;110(52):21 101-21 106. Doi.org/10.1073/pnas.1306072110
74. Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA 1996;93(15):7861-4 doi: 10.1073/pnas.93.15.7861.
75. Hollis BW, Wagner CL. The Role of the Parent Compound Vitamin D with Respect to Metabolism and Function: Why Clinical Dose Intervals Can Affect Clinical Outcomes. J Clin Endocrinol Metab. 2013;98(12):4619-28 Doi.org/10.1210/jc.2013-2653
76. Gombash SE, Lee PW, Sawdai E, Lovett-Racke EE. Vitamin D as a Risk Factor for Multiple Sclerosis: Immunoregulatory or Neuroprotective? Front Neurol. 2022;13:796933
77. Mayne PE, Burne THJ. Vitamin D in Synaptic Plasticity, Cognitive Function, and Neuropsychiatric Illness. Trends Neurosci. 2019;42(4).293-306
78. Holick MF. Vitamin D and brain health: the need for vitamin D supplementation and sensible sun exposure. J Intern Med. 2015;277(1)90-3
79. Eyles DW. Vitamin D: Brain and Behavior. JBMR Plus. 2020;5(1)/e10419
80. AlJohri R, AIOkai M, Haq SH. Neuroprotective role of vitamin D in primary neuronal cortical culture. Neurological Sci. 2019;14:43-48, doi. 10.1016/j.ensci.2018.12.004
81. Zorzella-Pezavento SFG, Mimura LAN, Denadai MB et al. Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis? Neurol. Regeneration Research. 2022;17(9):1945-1954, DOI: 10.4103/1673-5374.335139
82. Boltjes R, Knippenberg S, Gerlach O, Hupperts R, Damoiseaux J. Vitamin D supplementation in multiple sclerosis: An expert opinion based on the review of current evidence. Expert Rev Neurother. 2021;21(6):715-725
83. Smolders J, Torkildsen O, Camu W, Holmoy T. An Update on vitamin D and disease Activity in Multiple Sclerosis. CNS Drugs. 2019;33(12):1187-1199
84. García Menéndez S, Giménez VMM, Holick MF, Barrantes FJ, and Manucha W. COVID-19 and neurological sequelae: Vitamin D as a possible neuroprotective and/or neuroreparative agent. Life Sci. 2022 May 15; 297: 120464.Published online 2022 Mar 7. doi: 10.1016/j.lfs.2022.120464
85. Xu Y, Baylink DJ, Chen CH-S, et al. The importance of vitamin D metabolism as a potential prophylactic, immunregulatory and neutroprotective treatment for COVID-19. J Transl Med 2020;18:322
86. Abbatemarco JR, Fox RJ, Li H, and Ontaneda D. Vitamin D and MRI Measures in Progressive Multiple Sclerosis. Mult Scler Relat Disord. 2019; 35: 276–282. Doi.10.1016/j.msard.2019.08.014
87. Longinetti E, Bower H, McKay KA, Englund S, Burman J, Fink K et al. COVID-19 clinical outcomes and DMT of MS patients and population-based controls. ACTN 2022, First publ. 22 August
88. Cauchi M, Willis M, Adrews A, et al. Multiple sclerosis, and the risk of infection: association of British Neurologists consensus guideline. Pract Neurol. 2022
89. Ballering AV, van Zon SKR, Hartman TC, Rosmalen J GM et al. Persistence of somatic symptoms after COVID-19 in the Netherland. an observational cohort studies. Lancet. 2022;400:452-61
90. Gerhard A, Prüß H, Franke C. Manifestations of the central nervous system after COVID-19. Nervenarzt. 2022;93:769-778
91. Orry B, Szekeres-Bartho J, Bizzarri M, Spiga AM, Unfer V. Inhibitory effects of Vitamin D on inflammation and IL-6 release. A further support for COVID-19. Eur Rev Med Pharmacol Sci. 2020;24:8187-8193
92. Silberstein M. COVID-19 and IL-6: Why vitamin D (probably) helps but tocilizumab might not. Eur J Pharmacol. 2021;899:174031
93. Campi I, Gennari L, Merlotti D, et al. Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy. BMC Infectious Diseases. 2021;21:566
94. Malaguanera L. Vitamin D3 as potential treatment adjuncts for CORONA-19. Nutrients. 2020; 12(11) 3512
95. Gönen MS, Alaylioglu M, Durcan E, et al. Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-COV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1. Nutrients. 2021;13(11):4044
96. Garjani A, Middleton RM, Nicholas R, Evangelou N. Recovery From COVID-19 in Multiple Sclerosis. Neurology: Neuroimmunology and Neuroinflammation 2022;9,e1118
97. Glinsky, G. Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells. Biomedicines. 2020; 8(5):129
98. Chiodini I, Gatti D, Soranna D, Merlotti D, Mingiano Ch, Fassio A et al. Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes. Front Public Health. 2021;9:736665
99. Petrelli F, Luciani A, Perego G, et al. Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analyses of 43 observational studies. J Steroid Biochem Mol Biol. 2021;211:105883
100. Fiorino S, Zippi M, Gallo C, et al. The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities. Br J Nutr. 2020; online 24 July 2020
101. Peng M-Y, Liu W-Ch, Zheng J-Q, et al. Immunological Aspects of SASRS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D. Int J Mol Sci. 2021;22(10):5251
102. Chiu SK. Putative Role of Vitamin D for COVID-19 Vaccination. Int Sci. J Mol. 2021:22(16):8988
103. Goncalves-Mendes N, Talvas J, Dualè C, et al. Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons. Front Immunol. 08 Febr 2019
104. Chillon TS, Demircan K, Heller RA, et al. Relationship between Vitamin D Status and Antibody Response to COVID-19 mRNA Vaccination in Healthy Adults. Biomedicines,18 Nov. 2021
105. Grant WB, Lahore H, McDonell SL, et al. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Death. Nutrients. 2020;12(4):988
106. Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment, and prevention. Rev Endocr Metab Disord. 2017;18:153-65
107. Dobson R, Cock HR, Brex P, Giovannoni G. Vitamin D supplementation. Pract. Neurol. 2018;18:35-42
108. Wimalawansa S. Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections-Sepsis and COVID-19. Nutrients. 2022;14(14):2997
109. Bae JH, Choe HJ, Holick MF. Lim S. Association of vitamin D status with COVID-19 and its severity: Vitamin D and COVID-19: a narrative review. Rev Endocrine Disord 2022;23(3):579-599
110. Martineau AR, Jolliffe DA, Greenberg L, et al. Vitamin D supplementation to prevent acute respiratory tract infections: individual participant data meta-analysis. Health Technol Assess. 2019;23(2):1-44
111. Helde-Frankling M, Björkhem-Bergman L. Vitamin D in Pain Management. Int J Mol Sci. 2017;18:2170.
112. Hollis BW, Wagner CL, The Role of the Parent Compound Vitamin D with Respect to Metabolism and Function. Why Clinical Dose Intervals Can Affect Clinical Outcomes. J Clin Endocrinol Metab. 2013;98:4619-4628
113. Feige J, Moser T, Bieler L. Schwenker K, Hauer L Sellner J. Vitamin d Suoolementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats. Nutrients. 2020;12(3):783
114. Calton EK, Keane KN, Newsholme P, Soares MJ. The impact of Vitamin D levels on Inflammatory Status: A systematic Review of Immune Cell Studies. PLoS One 2015;10(11):e0141770
115. Shoemaker TJ, Mowry EM. A review of vitamin D supplementation as disease-modifying therapy. Mult Scler. 2018;24(1).6-11
116. Wesnes K, Myhr K-M, Riise T, Kvistad SS, Torkildsen O, Wergeland S et al. Low vitamin D, but not tobacco use or high BMI, is associated with long-term disability progression in multiple sclerosis. Mult Scler Relat Disord. 2021;50:102801
117. Jetty V; Lueck CJ, Wang P, et al. Safety of 50,000-100,000 Units of Vitamin D3/Week in vitamin D-Deficient, Hypercholesterolemic patients with reversible Statin Intolerance. N Am J Med Sci. 2016;8(3):156-162
118. Sotirchhos ES, Bhargave P, Eckstein C, Van Haren K, Baynes M, Nitranos A. Safety, and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. Neurology. 2016;86(4):382-390
119. Häusler D, Torke S, Peelen E, Bertsch T, Djukic M, Nau R et al. High dose vitamin D exacerbation central nervous system autoimmunity by raising T cell excitatory calcium. Brain. 2019;142:2737-55
120. Carlberg C, Haq A. The concept of the personal vitamin D response index. J Steroid Biochem Mol Biol. J 2018;175,12-17
121. Mapunda JA, Tibar H, Regragui W, Engelhardt B. How Does the Immune System Enter the Brain? Front Immunol. 2022;13:805657
122. Engelhardt B, Comabella M, Chan A. Multiple sclerosis: Immunopathological heterogeneity and its implications. Eur J Immunol. 2022;52(6):869-881
123. Kuhlmann J. et al. Multiple sclerosis progression: time for a new mechanism – driven framework. Lancet Neurol 2022, publ. online. 18.Nov.2022
124. Cagol A et al. Association of brain atrophy with disease progression independent of relapse activity in patients with relapsing multiple sclerosis. JAMA Neurology 2022;79(7):682-692
125. Absinta M et al. Association of chronic active multiple sclerosis lesions with disability in vivo. JAMA Neurol 2019;76(12):1474-1483.
126. Spanier JA et al. Vitamin D3-mediated resistance to a multiple sclerosis model disease depends on myeloid cell 1,15-dihydroxyvitamin D3 synthesis and correlates with increased CD4+ T cell CTLA-4 expression. J Neuroimmunology 2019:338:577105
127. Radandish M et al. The role of distinct subsets of macrophages in the pathogenesis of MS and the impact of different therapeutic agents on these population. Front Immunol 2021;12:667705
128. Wang J et al. Targeting microglia and macrophages: A potential treatment strategy for multiple sclerosis. Front Pharmacol 2019;10:286
129. Lee, PW et al. Neuron-specific vitamin d signaling attenuates microglia activation and CNS autoimmunity. Front Neurol 2020;11:19