Seasonal Patterns in Autoimmune Diseases: What the Science Shows

By Hugo Francisco de SouzaReviewed by Benedette Cuffari, M.Sc.

Introduction
The seasonality of autoimmunity
Temperature, climate, and disease prevalence worldwide
Birth month and autoimmunity: A seasonal signature
New insights into seasonal immune regulation
Mechanisms involved in seasonal activity
Disease examples
Clinical implications
Future research directions
References
Further reading

Seasonal changes in temperature, sunlight, and circadian biology are strongly associated with shifts in immune regulation and autoimmune disease activity, influencing prevalence, flare patterns, and early-life risk signatures such as birth month. Integrating ecological, molecular, and clinical evidence reveals that environmental seasonality interacts with genetic and epigenetic mechanisms to shape autoimmune vulnerability across the lifespan.

Image Credit: Corona Borealis Studio / Shutterstock.com

Introduction

This article discusses how sunlight, temperature, and circadian biology shape autoimmune response and how monitoring disease seasonality could inform predictive, chronobiology-based care.

The seasonality of autoimmunity

Autoimmune diseases are characterized by an excessive immune response that causes the host's immune system to attack its own healthy tissues, organs, and cells.¹ Clinical manifestations of autoimmune diseases vary from joint destruction observed in rheumatoid arthritis to pancreatic beta-cell elimination in type 1 diabetes (T1D).

Although individual autoimmune diseases differ biologically, they share environmental influences that vary based on seasonality. Data indicate that seasonal cycles modulate epigenetic effects like DNA methylation and micro-ribonucleic acid (RNA) (miRNA) expression to disrupt immune tolerance without altering the host's underlying genomic sequences.¹

A pivotal 2024 pilot study provided direct evidence of seasonal fluctuations in specific T-cell subsets. Herein, researchers compared T-cell profiles in females between late summer and late winter and found a higher percentage of regulatory T cells (Tregs) in summer (7.3%) than in winter (7%), with naïve Tregs 13% higher in adult women in summer. These differences were observed in a small cohort (n=29) in Hobart, Australia, and therefore require validation in larger populations.²

Although inflammatory Th17 levels did not significantly change overall, a significant negative correlation was observed in adult women. Specifically, those who spent more hours outdoors in summer had lower Th17 levels than those who remained indoors.²

Temperature, climate, and disease prevalence worldwide

Large-scale ecological analyses have established a thermal signature for autoimmunity. For example, a recent 2025 study analyzing data from 201 countries identified a significant inverse correlation between average annual temperature (AAT) and the age-standardized prevalence of five major autoimmune diseases.³

Linear regression analyses revealed that T1D exhibited the strongest association with cold climates, with approximately 48% of cross-country variation in prevalence explained by average annual temperature (AAT) in the regression model (adjusted R²≈0.48), suggesting a substantial ecological association.³ Inflammatory bowel disease (IBD) and psoriasis also exhibited strong associations with colder regions, whereas rheumatoid arthritis possessed a moderate thermal association.³

Together, these findings suggest that environmental exposures associated with lower temperatures, such as reduced sunlight, vitamin D deficiency, and pathogen prevalence, may contribute to a permissive environment for autoimmunity globally, although ecological analyses cannot establish causation and may be confounded by socioeconomic or genetic factors.^1,3

Image Credit: Seventy Four / Shutterstock.com

Birth month and autoimmunity: A seasonal signature

Seasonal factors act as immediate triggers for autoimmune manifestations; however, early-life exposures, such as the season of birth, may similarly predict autoimmune outcomes.^3,4

A 2022 systematic review of 11 studies found that 73% identified a significant seasonal pattern in the birth months of patients who subsequently developed autoimmune endocrine diseases, with 64% of included studies identifying birth peaks in spring and/or summer.⁴ Seasonality appeared more pronounced in Hashimoto’s thyroiditis and in women.⁴

The vitamin D hypothesis posits that winter gestation results in maternal vitamin D deficiency, which ultimately affects fetal thymic development. Comparatively, the viral infection hypothesis posits that perinatal exposure to seasonal viruses induces autoimmunity through molecular mimicry.⁴

New insights into seasonal immune regulation

Approximately 23% of the human genome, including critical immune genes, exhibits significant seasonal variation in expression.⁵ During winter, the immune system often shifts toward a proinflammatory profile characterized by upregulated C-reactive protein (CRP) and interleukin-6 (IL-6) receptor levels. This winter immunocompetence likely evolved to combat infectious pathogens; however, it also reduces the threshold for autoimmune inflammation in genetically susceptible individuals.⁵

Circadian clock genes, such as BMAL1 (ARNTL), have also been implicated in autoimmune regulation; experimental lupus models demonstrate that myeloid-specific Bmal1 deficiency increases autoantibody production and immune complex deposition, whereas human neutrophil BMAL1 expression correlates with disease serology.⁸

Melatonin, a light-regulated neurohormone whose secretion peaks at night, exerts antioxidant and immunomodulatory effects and has been associated with seasonal immune variation; however, its effects in autoimmune diseases such as rheumatoid arthritis appear mixed and context-dependent.⁹

Mechanisms involved in seasonal activity

Sunlight/UV and vitamin D

Autoimmune patients often have vitamin D insufficiency, defined as concentrations below 20 ng/mL, with several studies reporting a correlation between vitamin D levels and disease activity.^4,6 The active metabolite of vitamin D is 1,25(OH)₂D₃, which suppresses Th1 and Th17 cytokines while upregulating Tregs.⁶ Clinical trial data in autoimmune diseases show heterogeneous results, with some studies reporting reduced relapse rates or treatment escalation needs in deficient individuals, whereas others demonstrate no significant benefit; therefore, supplementation should be individualized and primarily aimed at correcting deficiency rather than routine high-dose use in vitamin D–replete individuals.⁶

Infections

Winter is associated with increased rates of respiratory viral infections, which are potential triggers of autoimmune disease. Severe influenza infections can induce immune hyperactivation and have been associated with autoimmune manifestations such as Guillain–Barré syndrome and type 1 diabetes. Proposed mechanisms include molecular mimicry, epitope spreading, and dysregulated cytokine responses, although infection alone is typically insufficient to induce autoimmunity in the absence of underlying genetic or immune susceptibility.⁷

Disease examples

Rheumatoid arthritis and psoriasis

Seasonal cycles affect immune gene expression and epigenetic regulation in rheumatoid arthritis, including DNA methylation and miRNA expression changes linked to inflammatory pathways.¹ Rheumatoid arthritis patients frequently report symptom worsening during colder months.¹

Psoriasis patients similarly experience winter severity. Environmental factors such as reduced ultraviolet radiation, lower humidity, and circadian rhythm shifts may influence genetic and epigenetic pathways involved in keratinocyte differentiation and immune signaling.⁵

IBD

A 2022 systematic review and meta-analysis found a statistically significant but weak correlation between seasonal variation and IBD exacerbation (pooled φc = 0.11), with considerable heterogeneity across studies and limited ability to identify a single consistent peak season.¹⁰

Clinical implications

Patients with autoimmune diseases may benefit from seasonal awareness strategies, including monitoring vitamin D status and maintaining appropriate supplementation when deficiency is confirmed.⁶

Influenza vaccination strategies are considered important for preventing severe infection and potentially reducing infection-triggered autoimmune exacerbations.⁷

Future research directions

Future research is needed to establish causality between seasonal differences and autoimmunity by tracking molecular signatures, including circadian gene expression (e.g., BMAL1), and by longitudinal immune profiling in large cohorts.⁸ Public health policymakers must also consider the potential impact of climate change on global autoimmune epidemiology, particularly in diseases with strong temperature associations.³

1. Priya, E. K. K., Shidhi, P. R., Sreedevi, S., & Banerjee, M. (2025). Impact of seasonal cycle on rheumatoid arthritis based on genetic and epigenetic mechanisms. Frontiers in Immunology 16. DOI: 10.3389/fimmu.2025.1601767. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1601767/full.
2. Clark, M. S., Christie, M., Jones, M., et al. (2024). Seasonal variation in sunlight exposure is differently associated with changes in T regulatory and T-helper 17 cell blood counts in adolescent and adults females: a pilot study. Photochemical & Photobiological Sciences 24(1); 23-35. DOI: 10.1007/s43630-024-00668-6. https://link.springer.com/article/10.1007/s43630-024-00668-6
3. Voskarides, K., Philippou, S., Hamam, M., & Parperis, K. (2025). Prevalence of autoimmune diseases is strongly associated with average annual temperatures: systematic review and linear regression analysis. BMC Rheumatology 9(1). DOI: 10.1186/s41927-025-00532-9. https://link.springer.com/article/10.1186/s41927-025-00532-9
4. Ramos-Leví, A. M., Collado, G., & Marazuela, M. (2022). Seasonality of month of birth in patients with autoimmune endocrine diseases: A systematic review. Endocrinología, Diabetes y Nutrición 69(10); 779-790. DOI: 10.1016/j.endinu.2021.10.016. https://www.elsevier.es/en-revista-endocrinologia-diabetes-nutricion-english-ed--413-pdf-S2530018022001810
5. Niedźwiedź, M., Skibinska, M., Ciazynska, M., et al. (2024). Psoriasis and Seasonality: Exploring the Genetic and Epigenetic Interactions. International Journal of Molecular Sciences 25(21); 11670. DOI: 10.3390/ijms252111670. https://www.mdpi.com/1422-0067/25/21/11670
6. Su, S., Shih, P., & Wu, M. (2025). High-dose Vitamin D supplementation for immune recalibration in autoimmune diseases. Frontiers in Immunology 16. DOI: 10.3389/fimmu.2025.1625769. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1625769/full
7. Xie, S., Wei, J., & Wang, X. (2025). The intersection of influenza infection and autoimmunity. Frontiers in Immunology 16. DOI: 10.3389/fimmu.2025.1558386. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1558386/full
8. Nakabo, S., Sandoval-Heglund, D., Hanata, N., et al. (2024). The circadian clock gene BMAL1 modulates autoimmunity features in lupus. Frontiers in Immunology 15. DOI: 10.3389/fimmu.2024.1465185. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1465185/full
9. Ahmad, S. B., Ali, A., Bilal, M., et al. (2023). Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders. Cellular and Molecular Neurobiology 43(6); 2437-2458. DOI: 10.1007/s10571-023-01324-w. https://pmc.ncbi.nlm.nih.gov/articles/PMC9907215/
10. Moon, S. J., Lee, Y. C., Kim, T. J., et al. (2022). Effects of temperature, weather, seasons, atmosphere, and climate on the exacerbation of inflammatory bowel diseases: A systematic review and meta-analysis. PLOS ONE 17(12). DOI: 10.1371/journal.pone.0279277. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0279277

Further Reading

• All Autoimmune Disease Content
• What is Autoimmune Disease?
• Types of Autoimmune Disease
• Autoimmune Disease Development Of Therapies
• The Hygiene Hypothesis and Autoimmune Disorders

Last Updated: Feb 18, 2026