What is known about the effects of vitamin D in neuropsychiatric lupus?

Karnopp, Thaís Evelyn; Freitas, Vinicius da Silva; Domenico, Andressa Leite Di; Chapacais, Gustavo Flores; Santos, Natália Garcia dos; Freitas, Eduarda Correa; Gasparin, Andrese Aline; Monticielo, Odirlei André

doi:10.1186/s42358-023-00344-w

Thaís Evelyn Karnopp ^**Correspondence: Thaís Evelyn Karnopp tekarnopp@gmail.com

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Laboratory of Autoimmune Diseases, Division of Rheumatology, Hospital de Clínicas de Porto Alegre, Centro de Pesquisas Experimentais, Universidade Federal Do Rio Grande Do Sul, Rua Ramiro Barcelos, 2350, Sala 12109, Porto Alegre 90035-003, Brazil.

Postgraduate Program in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.

http://orcid.org/0000-0002-8013-3510

Vinicius da Silva Freitas

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Laboratory of Autoimmune Diseases, Division of Rheumatology, Hospital de Clínicas de Porto Alegre, Centro de Pesquisas Experimentais, Universidade Federal Do Rio Grande Do Sul, Rua Ramiro Barcelos, 2350, Sala 12109, Porto Alegre 90035-003, Brazil.

Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.

Andressa Leite Di Domenico

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Laboratory of Autoimmune Diseases, Division of Rheumatology, Hospital de Clínicas de Porto Alegre, Centro de Pesquisas Experimentais, Universidade Federal Do Rio Grande Do Sul, Rua Ramiro Barcelos, 2350, Sala 12109, Porto Alegre 90035-003, Brazil.

Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.

Gustavo Flores Chapacais

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Laboratory of Autoimmune Diseases, Division of Rheumatology, Hospital de Clínicas de Porto Alegre, Centro de Pesquisas Experimentais, Universidade Federal Do Rio Grande Do Sul, Rua Ramiro Barcelos, 2350, Sala 12109, Porto Alegre 90035-003, Brazil.

Postgraduate Program in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.

Natália Garcia dos Santos

Text review and corrections were performed

commented on the manuscript

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Laboratory of Autoimmune Diseases, Division of Rheumatology, Hospital de Clínicas de Porto Alegre, Centro de Pesquisas Experimentais, Universidade Federal Do Rio Grande Do Sul, Rua Ramiro Barcelos, 2350, Sala 12109, Porto Alegre 90035-003, Brazil.

Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.

Postgraduate Program in Biological Sciences: Pharmacology and Therapeutics, Porto Alegre, RS, Brazil.

Eduarda Correa Freitas

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Laboratory of Autoimmune Diseases, Division of Rheumatology, Hospital de Clínicas de Porto Alegre, Centro de Pesquisas Experimentais, Universidade Federal Do Rio Grande Do Sul, Rua Ramiro Barcelos, 2350, Sala 12109, Porto Alegre 90035-003, Brazil.

Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.

Andrese Aline Gasparin

Text review and corrections were performed

commented on the manuscript

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Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.

Odirlei André Monticielo

Text review and corrections were performed

commented on the manuscript

read and approved the final manuscript

Laboratory of Autoimmune Diseases, Division of Rheumatology, Hospital de Clínicas de Porto Alegre, Centro de Pesquisas Experimentais, Universidade Federal Do Rio Grande Do Sul, Rua Ramiro Barcelos, 2350, Sala 12109, Porto Alegre 90035-003, Brazil.

Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.

*Correspondence: Thaís Evelyn Karnopp tekarnopp@gmail.com

Competing interests

None.

Central nervous system	Peripheral nervous system
Aseptic meningitis	Acute inflammatory demyelinating polyradiculoneuropathy
Cerebrovascular disease	(Guillain–Barre syndrome)
Demyelinating syndrome	Autonomic disorder
Headache (including migraine and benign intracranial hypertension)	Myasthenia gravis
Movement disorder (chorea)	Cranial neuropathy
Myelopathy	Plexopathy
Seizure disorders	Polyneuropathy
Acute confusional state
Anxiety disorder
Cognitive dysfunction
Mood disorder
Psychosis

Author	Animal models			Humans
Author	Yan et al. (⁷⁰70 Yan L, Wu P, Gao DM, Hu J, Wang Q, Chen NF, et al. The impact of Vitamin D on cognitive dysfunction in mice with systemic lupus erythematosus. Med Sci Monit. 2019;25(25):4716–22.)	Karnopp et al. (¹⁸18 Karnopp TE, Freitas EC, Rieger A, Chapacais GF, Monticielo OA. Higher IgG level correlated with vitamin D receptor in the hippocampus of a pristane-induced lupus model. Clin Rheumatol. 2022;14:1859.)	Li et al. [⁷¹71 Li X, Xu S, Liu J, Zhao Y, Han H, Li X, et al. Treatment with 1,25-Dihydroxyvitamin D3 Delays Choroid Plexus Infiltration and BCSFB Injury in MRL/lpr Mice Coinciding with Activation of the PPARγ/NF-κB/TNF-α Pathway and Suppression of TGF-β/Smad Signaling. Inflammation. 2022.]	Tay et al. [⁶⁸68 Tay SH, Ho CS, Ho RCM, Mak A. 25-Hydroxyvitamin D3 deficiency independently predicts cognitive impairment in patients with systemic lupus erythematosus. Crispin J, editor. PLoS ONE. 2015;10(12):e0144149.]	Hussein et al. [⁴⁸48 Hussein HA, Daker LI, Fouad NA, Elamir A, Mohamed SR. Does Vitamin D deficiency contribute to cognitive dysfunction in patients with systemic lupus erythematosus? Innov Clin Neurosci. 2018;15(9–10):25–9.]	Sultana et al. (⁶⁹69 Sultana N, Sarkar AK, Matsuda H, Ihsan MA, Haq SA, Arefin MS, et al. Relationship between Vitamin D status and brain perfusion in neuropsychiatric lupus. Nucl Med Mol Imaging. 2022;56(3):158–68.)
Origin	China	Brazil	China	Singapore	Egypt	Bangladesh
Mouse model	MRL/lpr	Pristane-induced lupus	MRL/lpr	N/A	N/A	N/A
Summary	Twenty male MRIVIpr mice (aged 2 months) were divided into two groups: SLE and SLE+VD;ten male C57BL/6 J mice were used as the control group	Twenty-three female BALB/c mice (aged 2 months) were divided into three groups: control (CO), pristane-induced lupus (PIL) and PIL mice supplemented with VD (VD)	Forty-eight female MRL/Ipr mice (aged 2 months) were divided into two groups: VitD3-treated group and control group. Mice were euthanized at 0 weeks (T1), 2 weeks (T2), 4 weeks (T3) and 6 weeks (T4)	Cross-sectional study in which SLE patients and healthy controls were administered Automated Neuropsychological Assessment Metrics, evaluating total throughput score (TTS) and the Hospital Anxiety and Depression Scale (HADS), Levels of 25(OH) D3 and 25(OH)D were measured	Cross-sectional, case-control study for which thirty patients diagnosed with SLE were recruited along with twenty control individuals with no history of neurologic or psychiatric conditions. All subjects were submitted to a battery of neuropsychological tests. Blood samples were collected to assess serum molecules, including vitamin D	Cross-sectional study in which 19 patients under-going brain perfusion SPECT were retrospectively studied. All individuals had vitamin D serum level determined
Treatment	SLE-VD group was treated with Aerococcus and one daily intraperitoneal injection of Vitamin D (2 ug/kg/day) for 4 weeks	VD mice were supplemented with subcutaneous injections of Calcijex (2 μg/kg) every two days for 6 months	Mice in the VitD3-treated group received a 4 μg/kg 1,25-dihydroxivitamin D3 intraperitoneal injection twice a week for 3 weeks	N/A	N/A	N/A
Main outcomes	SLE+VD group presented: better performance on Morris maze test; less degeneration in the hippocampus; increased expression of VDR and Bcl-2 and decreased expression of Αβ and cleaved caspase-3 in the hippocampus	Positive correlation between VDR and IgG levels in the hippocampus of PIL and VD groups	VitD3-treated group presented: inhibited expression of genes related to cognitive dysfunction; decrease of pathological findings in brain tissues; decreased anti-dsDNA and increased C3 serum levels; increased expression of occludin and claudin-2 in the brain; increased PPAR-γ, BDNF, TGF-β TTβR-l, Smad2/3 and P-Smad2/3 expression; decreased NF-κΒ and TNF-α expression	SLE patients presented more 25(OH)D₃ deficiency than healthy controls; this deficiency predicted worse TTS; age was the only predictor of TTS	SLE patients presented significantly lower levels of seru m Vit-D compared with controls; there was a negative correlation between vitamin D serum levels and performance in executive function tests in the SLE group	Positive correlation between vitamin D serum level and brain perfusion

[1] *Correspondence: Thaís Evelyn Karnopp tekarnopp@gmail.com

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What is known about the effects of vitamin D in neuropsychiatric lupus?

Abstract