Immunological Disorders and Immunotherapy
Open Access

Exploring the Frontiers of Autoimmunity: From Pathogenesis to Treatment

Shang Li^{* *}Correspondence: Shang Li, Department of Immunology, Kyung Hee University, Seoul, South Korea, Email:

Author info »

Description

Autoimmunity is a growing concern in modern medicine, affecting millions of individuals globally. It occurs when the immune system mistakenly targets and attacks the body’s own tissues, leading to a wide range of disorders such as rheumatoid arthritis, lupus, multiple sclerosis, and type 1 diabetes. As the global prevalence of autoimmune diseases increases, understanding the mechanisms behind autoimmunity and developing novel treatment strategies becomes paramount.

The immune system is designed to defend the body against foreign invaders such as pathogens. However, in autoimmune diseases, this system becomes dysregulated and fails to distinguish between self and non-self. This results in an aberrant immune response directed at normal, healthy cells.

Genetic and environmental triggers in autoimmune disease

A critical factor in autoimmunity is genetic predisposition. Certain gene variants, especially those involved in immune regulation, can increase the risk of autoimmune conditions. Environmental factors like infections, diet, and toxins also contribute by triggering or exacerbating autoimmune responses in genetically predisposed individuals. Additionally, molecular mimicry where foreign pathogens share similar structures with self-antigens has been proposed as a mechanism through which infections may lead to the onset of autoimmune diseases.

T-cells, B-cells, and innate immune cells play central roles in the pathogenesis of autoimmunity. A malfunction in the regulation of T-cells, particularly helper T-cells (Th1 and Th17), leads to excessive inflammation and tissue damage in various autoimmune diseases. Similarly, autoreactive B-cells that produce autoantibodies are a hallmark of many autoimmune disorders such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA).

Loss of immune tolerance: A key driver of autoimmune disease

Another important component of autoimmune disease is the loss of immune tolerance. The immune system has mechanisms to prevent the activation of autoreactive lymphocytes, but when these processes fail, autoreactive cells can proliferate and initiate pathological responses. The breakdown of tolerance may involve altered antigen presentation, changes in cytokine networks, or defects in regulatory T-cells, which normally suppress autoreactive responses.

Despite significant progress, the treatment of autoimmune diseases remains a challenging task. The heterogeneity of these diseases, with their varying symptoms and progression, makes personalized treatment approaches crucial. Furthermore, the side effects of immunosuppressive therapies often limit their long-term use, underscoring the need for safer and more effective alternatives.

Conclusion

Future research should focus on further understanding the genetic and environmental triggers of autoimmunity. The development of precision medicine, which tailor’s treatment based on an individual’s genetic profile and immune response, holds promise for better management of these complex diseases. Additionally, strategies to restore immune tolerance and prevent disease flare-ups are emerging as key goals in autoimmune therapy.

References

1. Lind A, Naredi Scherman M, Hamdan S, Agardh D. Risk of celiac disease, type 1 diabetes, and thyroid disease autoimmunity during the SARS-CoV-2 pandemic in South of Sweden: Insights from the TRIAD study. Autoimmun. 2025;58(1):2490491.

   [Crossref] [Google Scholar] [PubMed]

2. Cucinella L, Barbagallo F, Erroi M, Procaccianti C, Martini E, Tiranini L et al. Signs and symptoms of vulvovaginal atrophy (VVA) in clinical practice the possible involvement of thyroid autoimmunity in Genitourinary Syndrome of Menopause (GSM). Gynecol Endocrinol. 2025;41(1):2458705.

   [Crossref] [Google Scholar] [PubMed]

3. Morel L. Animal models of autoimmunity: a relentless pursuit of accurate pre-clinical models. Editorial Autoimmun Rev. 2025;58(1):2461072.

   [Crossref] [Google Scholar] [PubMed]

4. Read C, Bhatia S, Totonchy M. Programmed cell death 1 blockade in the setting of severe ocular sarcoidosis: Cancer immunotherapy in a patient with autoimmunity. JAAD Case Rep. 2025;62:43-45.

   [Crossref] [Google Scholar] [PubMed]

5. Osinga JAJ, Derakhshan A, Karachaliou M, Poppe KG, Vaidya B, Mannisto T, et al. Association of gestational thyroid function and thyroid autoimmunity with gestational diabetes: A systematic review and individual participant meta-analysis. Lancet Diabetes Endocrinol. 2025;13(8):651-661.

   [Crossref] [Google Scholar] [PubMed]

6. Li SS, Li K, Li JY, Wang Y. CD137 might be a pivotal regulator of Th1/Th17-driven autoimmunity and B-cell hyperactivity in hyperthyroidism. Mol Immunol. 2025;184:89-99.

   [Crossref] [Google Scholar] [PubMed]

7. Li S, Liu H, Zeng S, Xie J. Corrigendum to safety of biologics in patients with autoimmune rheumatic diseases during pregnancy: Systematic review and meta-analysis. Autoimmun Rev. 2025;24(8):103840.

   [Crossref] [Google Scholar] [PubMed]

8. Heeringa P, Rutgers A. Triggering trouble: Post-translational modifications may drive myeloperoxidase autoimmunity. Kidney Int. 2025;S0085-2538(25)00480-00486.

   [Crossref] [Google Scholar] [PubMed]

9. Platt IS, Joseph A, Tsirka V, Raja N, Garcia M, Palace J, et al. Multiple autoimmunity: Neuromyelitis optica spectrum disorder with Lambert-Eaton myasthenic syndrome. Pract Neurol. 2025;25(4):345-348.

   [Crossref] [Google Scholar] [PubMed]

10. Gonzalez-Gronow M, Pizzo SV. Physiological roles of the autoantibodies to the 78-kilodalton glucose-regulated protein (GRP78) in cancer and autoimmune diseases. Biomedicines. 2022;10(6):1222.

    [Crossref] [Google Scholar] [PubMed]