Anti-vitamin D antibodies
Autoimmunity Reviews Volume 24, Issue 2, 31 January 2025
https://doi.org/10.1016/j.autrev.2024.103718 partial PDF with references
Jozélio Freire de Carvalho a, Thelma L. Skare b., Ana Tereza Amoedo Martinez c, Yehuda Shoenfeld d e
Background
Low vitamin D levels are commonly observed in autoimmune diseases, suggesting a potential role in disease pathogenesis. The presence of anti-vitamin D antibodies may contribute to these deficiencies and influence autoimmune processes.
Objective
To review and analyze studies investigating the occurrence of anti-vitamin D antibodies in autoimmune diseases.
Results
Three studies, comprising a total of 345 patients, were reviewed. The autoimmune conditions included
- systemic lupus erythematosus (SLE),
- scleroderma (SSc),
- primary antiphospholipid antibody syndrome (pAPS), and
- pemphigus vulgaris (PV).
Patient mean ages ranged from 26.8 to 31 years, with the proportion of female participants ranging from 87 % to 96 %. The duration of disease varied between 6.3 and 12.3 years. Serum vitamin D levels ranged from 11.71 ± 7.21 to 28.4 ± 9.6 ng/mL, with 57.1 % to 82.1 % of patients presenting vitamin D deficiency.
The prevalence of anti-vitamin D antibodies was reported as follows:
- 87 % in SSc,
- 11 % in PV,
- 4 % to 6.1 % in SLE, and
- 3.5 % in pAPS.
Associations with other disease markers were also noted: in SLE, anti-vitamin D antibodies were associated with anti-dsDNA antibodies; while in SSc, their presence was linked to the disease itself.
Conclusion
Anti-vitamin D antibodies were identified in 3.5 % to 87 % of patients with SLE, SSc, pAPS, and PV. These antibodies are associated either with the autoimmune condition itself or with other autoantibodies, suggesting their potential role in disease mechanisms and progression.
VitaminDWiki – Low Vitamin D strongly associated with Systemic Sclerosis - many studies
VitaminDWiki – Lupus
Report on Anti-Vitamin D Antibodies by Perplexity AI Deep Research - March 2025
Anti-Vitamin D Antibodies: Emerging Players in Autoimmune Pathophysiology
In recent years, there has been growing recognition of the complex relationship between vitamin D and autoimmune diseases, with increasing evidence suggesting that vitamin D deficiency may contribute to autoimmune pathogenesis. Intriguingly, a novel aspect of this relationship has emerged with the discovery of anti-vitamin D antibodies—autoantibodies directed against vitamin D itself. These antibodies represent a potentially important mechanism underlying vitamin D insufficiency in autoimmune conditions and may offer new insights into disease mechanisms, diagnosis, and treatment approaches. This report provides a comprehensive examination of current knowledge regarding anti-vitamin D antibodies, their prevalence across autoimmune diseases, associations with other disease markers, and implications for understanding and managing autoimmune disorders.
Discovery and Detection of Anti-Vitamin D Antibodies
Anti-vitamin D antibodies represent a relatively recent discovery in the field of autoimmunity. These antibodies target vitamin D molecules, potentially interfering with vitamin D metabolism and function. The detection of these autoantibodies has been accomplished primarily through enzyme-linked immunosorbent assay (ELISA) techniques specifically designed to identify antibodies against vitamin D 1 2. The development of these detection methods has allowed researchers to investigate the presence of these antibodies across various patient populations, particularly those with autoimmune disorders. Early studies employed ELISA techniques alongside parallel measurements of serum vitamin D concentrations, typically using commercial kits such as the DiaSorin LIAISON 25 OH vitamin D assay, to explore potential relationships between these antibodies and vitamin D status 1 2.
The identification of anti-vitamin D antibodies has opened a new avenue of research into vitamin D deficiency, which is commonly observed in autoimmune diseases. Before this discovery, low vitamin D levels in autoimmune conditions were primarily attributed to factors such as reduced sun exposure, inadequate dietary intake, genetic variations in vitamin D metabolism, or increased vitamin D utilization. The discovery of these antibodies suggests another potential mechanism for vitamin D deficiency in these populations—direct targeting of vitamin D molecules by the immune system itself 3. This represents a significant conceptual shift in understanding the complex relationship between vitamin D status and autoimmune disease pathophysiology.
Prevalence in Autoimmune Diseases
Research has revealed varying prevalence rates of anti-vitamin D antibodies across different autoimmune conditions. A review examining three studies with a total of 345 patients found notable differences in the frequency of these antibodies depending on the specific autoimmune disease 3. The highest prevalence was observed in systemic sclerosis (SSc), where an extraordinary 87% of patients demonstrated anti-vitamin D antibodies 3. This striking prevalence suggests these antibodies may play a particularly important role in SSc pathophysiology.
In contrast, other autoimmune conditions showed lower but still significant prevalence rates. Pemphigus vulgaris (PV) patients exhibited anti-vitamin D antibodies in approximately 11% of cases 1 2 3. In systemic lupus erythematosus (SLE), these antibodies were detected in 4-6.1% of patients across different studies 1 2 3. The lowest prevalence was observed in primary antiphospholipid antibody syndrome (pAPS), where only 3.5% of patients tested positive for these antibodies 1 2 3.
These varying prevalence rates across different autoimmune conditions suggest that anti-vitamin D antibodies may have disease-specific roles or mechanisms. The remarkably high prevalence in systemic sclerosis compared to other autoimmune diseases indicates that these antibodies might be particularly relevant to the pathogenesis or progression of SSc. Furthermore, the consistent detection of these antibodies across multiple autoimmune disorders, albeit at different rates, suggests they may represent a shared but variable autoimmune phenomenon deserving further investigation.
Relationship with Vitamin D Metabolism and Status
The relationship between anti-vitamin D antibodies and actual vitamin D levels in patients presents an intriguing area of study. Serum vitamin D levels in the studied autoimmune populations ranged from severely deficient (11.71 ± 7.21 ng/mL) to insufficient (28.4 ± 9.6 ng/mL), with 57.1% to 82.1% of patients presenting with vitamin D deficiency 3. This high rate of deficiency aligns with the established knowledge that low vitamin D status is commonly observed in autoimmune diseases, potentially contributing to disease pathogenesis through its effects on immune regulation 5 7 13.
Interestingly, one of the early studies examining anti-vitamin D antibodies in SLE found that vitamin D levels were similar in both patient groups with and without these antibodies 1 2. This somewhat counterintuitive finding raises important questions about the functional impact of these antibodies on vitamin D metabolism and bioavailability. It suggests that the presence of anti-vitamin D antibodies may not necessarily correlate with lower circulating vitamin D levels, at least in some patient populations.
Several possible explanations exist for this observation.
- The antibodies might target specific forms or metabolites of vitamin D not measured by standard 25-hydroxyvitamin D assays.
- Alternatively, they might affect vitamin D function rather than total concentration, perhaps by interfering with vitamin D binding to its receptor or transport proteins.
The vitamin D binding protein (DBP) plays a crucial role in vitamin D transport and storage in circulation [|EPR20695-90] - Abcam" 6, and antibodies potentially interfering with this carrier function could affect vitamin D bioavailability without necessarily changing total measured levels.
Associations with Other Autoantibodies and Clinical Features
A particularly notable finding regarding anti-vitamin D antibodies in SLE is their strong association with anti-dsDNA antibodies (p=0.0004) 1 2. Anti-dsDNA antibodies represent a hallmark serological marker in SLE, closely associated with disease activity and nephritis. This correlation suggests that anti-vitamin D antibodies may be linked to specific immunological profiles or disease subsets within SLE. It raises the possibility that these antibodies might emerge as part of broader autoantibody clusters with shared mechanisms or triggers.
Beyond this specific association, studies have examined whether the presence of anti-vitamin D antibodies correlates with various demographic and clinical variables. Demographic features including age and gender distribution did not appear to differ significantly between autoantibody-positive and autoantibody-negative groups 1 2. The mean ages of patients in these studies ranged from 26.8 to 31 years, with female participants comprising between 87% and 96% of the study populations 3. The duration of disease among studied patients varied between 6.3 and 12.3 years 3.
In SLE specifically, organ involvement patterns and SLE Disease Activity Index (SLEDAI) scores did not significantly differ between patients with and without anti-vitamin D antibodies 1 2. This suggests that these antibodies may not be directly associated with overall disease severity or specific organ manifestations in SLE. However, the strong association with anti-dsDNA antibodies indicates a potential relationship with immune dysregulation that warrants further investigation.
Potential Mechanisms and Pathogenic Role
The mechanisms by which anti-vitamin D antibodies might contribute to autoimmune pathogenesis remain incompletely understood. However, several hypotheses have emerged based on our understanding of vitamin D's role in immune regulation. Vitamin D is recognized as an important natural immune modulator with multiple effects on both innate and adaptive immunity 5 13. It influences the behavior of various immune cells including macrophages, dendritic cells, and T cells, generally promoting a more tolerogenic and less inflammatory environment 14.
Anti-vitamin D antibodies could potentially disrupt these immunomodulatory effects by binding to vitamin D molecules and preventing their interaction with vitamin D receptors (VDR) on immune cells. The VDR is expressed in virtually all immune cells, making them susceptible to vitamin D-mediated modulation 14. By interfering with this signaling pathway, anti-vitamin D antibodies might contribute to immune dysregulation and promote autoimmune processes.
Another potential mechanism relates to vitamin D's role in B cell function and autoantibody production. Research indicates that vitamin D decreases antibody production and may induce IL-10 expression in B cells through direct VDR binding to the IL-10 promoter region 14. If anti-vitamin D antibodies disrupt these regulatory effects, they could potentially contribute to B cell hyperactivity and increased autoantibody production, perpetuating the autoimmune process.
In systemic sclerosis, where the prevalence of anti-vitamin D antibodies is remarkably high, these antibodies might play a more direct pathogenic role. The association of these antibodies with SSc itself suggests they may be intricately linked to disease-specific mechanisms 3. Given vitamin D's reported effects on fibroblast function and extracellular matrix production, interference with these pathways could potentially contribute to the characteristic fibrosis seen in SSc.
Implications for Diagnosis and Treatment
The discovery of anti-vitamin D antibodies opens new possibilities for diagnosis and treatment of autoimmune diseases. From a diagnostic perspective, testing for these antibodies may provide additional information about a patient's immunological profile and potentially help identify specific disease subsets. The strong association with anti-dsDNA antibodies in SLE suggests that anti-vitamin D antibodies might serve as part of an expanded autoantibody panel for more comprehensive immune assessment 1 2.
Therapeutically, understanding the role of these antibodies could inform more targeted treatment approaches. If anti-vitamin D antibodies significantly contribute to vitamin D deficiency or resistance in certain patients, standard vitamin D supplementation strategies might need reconsideration. Higher doses or alternative delivery methods might be necessary to overcome antibody-mediated interference. Additionally, the development of therapies specifically targeting these antibodies or preventing their production could potentially represent a novel treatment strategy.
Several clinical trials have explored vitamin D supplementation in autoimmune diseases, with some showing promising results. In SLE specifically, studies supplementing either 2,000 IU daily or 50,000 IU weekly have demonstrated decreasing disease activity scores, autoantibody levels, and fatigue 14. However, whether these effects are modified by the presence of anti-vitamin D antibodies remains to be determined. Future supplementation studies should consider screening for these antibodies to evaluate whether they influence treatment response.
Conclusion and Future Research Directions
Anti-vitamin D antibodies represent an intriguing development in our understanding of the complex relationship between vitamin D and autoimmunity. Their detection across multiple autoimmune diseases, particularly at high rates in systemic sclerosis, suggests they may play important roles in disease pathophysiology. The association with anti-dsDNA antibodies in SLE further indicates potential connections to established autoimmune mechanisms.
Future research should focus on several key areas to advance our understanding of these antibodies. Larger epidemiological studies are needed to more precisely determine prevalence rates across different autoimmune conditions and population demographics. Functional studies investigating how these antibodies interact with vitamin D and whether they genuinely impair vitamin D signaling would provide crucial mechanistic insights. Additionally, longitudinal studies tracking antibody levels over time in relation to disease activity and vitamin D status could help clarify their clinical significance.
Perhaps most importantly, the therapeutic implications of these antibodies require further exploration. Clinical trials of vitamin D supplementation should incorporate testing for anti-vitamin D antibodies to determine whether their presence predicts treatment response. Novel therapeutic approaches targeting these antibodies directly might also deserve investigation as potential treatments for autoimmune diseases, particularly those with high antibody prevalence such as systemic sclerosis.
As research in this area continues to evolve, anti-vitamin D antibodies may emerge as important biomarkers and therapeutic targets, potentially reshaping our approach to vitamin D deficiency in autoimmune diseases. Their discovery highlights the complexity of vitamin D metabolism in autoimmunity and underscores the importance of considering autoantibody-mediated processes in our understanding of these challenging conditions.
Perplexity AI Citations:
- https://pubmed.ncbi.nlm.nih.gov/17785344/
- https://nyaspubs.onlinelibrary.wiley.com/doi/10.1196/annals.1398.061
- https://pubmed.ncbi.nlm.nih.gov/39653259/
- https://www.medixbiochemica.com/anti-vitamin-25-700016
- https://pmc.ncbi.nlm.nih.gov/articles/PMC5247472/
- https://www.abcam.com/en-us/products/primary-antibodies/vitamin-d-binding-protein-antibody-epr20695-90-bsa-and-azide-free-capture-ab244658
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3149865/
- https://ashpublications.org/thehematologist/article/doi/10.1182/hem.V20.1.2023110/494123/No-Shoes-No-Shirt-No-Thrombus-Could-Vitamin-D
- https://www.abcam.com/en-us/products/primary-antibodies/vitamin-d-receptor-antibody-ab3508
- https://www.nature.com/articles/s41598-024-67588-4
- https://pubmed.ncbi.nlm.nih.gov/38206745/
- https://www.biocompare.com/pfu/110447/soids/423215/Antibodies/vitamin_D
- https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2015.00513/full
- https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00697/full
- https://www.mdpi.com/1422-0067/23/17/9784
- https://www.genetex.com/Product/Detail/Vitamin-D-Binding-Protein-antibody/GTX64444
- https://www.sigmaaldrich.com/US/en/product/sigma/sab4503071
- https://www.pocn.com/anti-vitamin-d-antibodies-and-systemic-lupus-erythematosus-pathogenesis/
- https://onlinelibrary.wiley.com/doi/abs/10.1196/annals.1398.061
- https://www.openrheumatologyjournal.com/VOLUME/12/PAGE/248/FULLTEXT/
Autoimmune Vitamin D Antibodies MAY only be affecting the Vitamin D genes
Perplexity AI March 2025 Report
VitaminDWiki - chart of Vitamin D Genetics