The Immunological Disorders Related to Ankylosing Spondylitis

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The immunological disorders related to ankylosing spondylitis

1 Introduction

1.1 Immunological disorders

The immune system generally consists of immune organs, different immune cells,

immune molecules (antibodies, comple ments, cytokines, etc.), and controls immune

responses(Wenker & Quint, 2024). Immunological disorders usually refer to

abnormalities in immune system function. Common immune disorders include the

following. First, low immune function. As the immune function of organism is reduced,

the ability to fight pathogens and tumors is accordingly reduced. Besides, allergic

reactions, where the immune system overreacts to harmless antigens, such as allergic

rhinitis, asthma, etc. (Wang et al., 2023). In addition, autoimmune diseases, due to

incorrect recognition by the immune system, which attacks the normal tissues of the

body, such as systemic lupus erythematosus, ankylosing spondylitis, etc. What’s more,

immunodeficiency diseases, immune insufficiency caused by partial loss of the immune

system, including nude mice, SCID rat, etc. This article will mainly introduce the

mechanism and views of immunological disorders related to ankylosing spondylitis.

1.2 Ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the axial spine.

It is a type of autoimmune diseases (Wenker & Quint, 2024). For patients with AS, the

spine, sacroiliac joints, and peripheral spine joints are usually affected, accompanied

by related symptoms such as abnormal spinal activity and chronic back pain(Fei et al.,

2024). In addition, AS may also cause inflammatory reactions in other organs. Common

complications include the following three. More than 50% of AS patients also suffer from

inflammatory bowel disease, approximately 30% of AS patients acquire acute anterior

uveitis, and almost 10% of AS patients develop psoriasis (Wenker & Quint, 2024). The

incidence of AS accounts for approximately 1% to 3% of the total

population (Qin et al., 2024), and is most common in young adult males.

Epidemiological data research shows that inflammation and immune factors are closely

related to AS, and 90% of AS patients are HLA-B27 positive. Currently, nonsteroidal

anti-inflammatory drugs, methotrexate and some new biosynthetic agents are

commonly used drugs to treat AS, but specific drugs are still lacking. What’s worse,

traditional drugs have shortcomings such as slow onset of action, gastrointestinal

discomfort, and poor adaptability; new biological agents are also very expensive,

bringing economic burdens to families and society. Therefore, it is very important to

explore the immunological disorders mechanism related to ankylosing spondylitis,

which can provide more options for the subsequent development of targeted drugs.

2 T cell-mediated autoimmune process in AS

The known genetic cause of AS is the HLA-B27 genotype (accounting for more than

90%) (Alotaibi et al., 2024). Currently, the pathogenesis of AS is unclear. However,

many studies have shown that T cell-mediated immune response is an important cause

of AS. First, a wide variety of genes exert a great function in the activation and

differentiation of T cells. When Th17 clears extracellular bacteria and fungi, it plays a

key and decisive role in maintaining the stable state of tissues and regulating

inflammatory responses. Th17 can produce IL-17A, which plays an extremely critical

role in the pathogenic sequence that leads to inflammation and destruction of joint tissue

in the process of activating and triggering a series of reactions (Groen et al., 2024).

Many studies have shown that IL-17A inhibitors can effectively suppress AS disease,

but only a portion (65%) of patients have significantly alleviated their symptoms

(Rosenzweig et al., 2024). It is suggested that there are multiple conditions of AS,

including Th17-dependent and -independent. Further research found that only when the

presence of IL-23 is required, can Th17 cells contribute to the pathogenesis of AS.

IL23R is closely related to Th17 immune response. Under normal physiological

conditions, IL-23R can maintain the integrity of mucosal surfaces and help eliminate

pathogens; however, in AS patients, it is overactivated (Rodolfi et al., 2023). TYK2,

IL27, IL6R genes have an important impact on the IL-23 pathway. And they have

also been found to be associated with AS. Among them, the signal transduction process of

IL-6 works through IL-6R and TGF-β (Zhao et al., 2024). Together, they exert effects

on specialized T lymphocytes, particularly Th17 cells, as well as on a specific subset of

regulatory T cells (Tregs). IL-6 signaling promotes Th17 cell differentiation from naive T cells. In the same time, it also inhibits the differentiation to Treg cells which is induced by transforming growth factor-β (Lin et al., 2024). Regulatory T cells, which is one special type of T lymphocytes, play a crucial role in maintaining the body's immune self-tolerance and homeostasis. The immune disorder mediated by T cells caused by various factors is an important reason for the occurrence and development of AS. In addition, other studies have further found that H3K27me3, a repressive histone modification, have ability to cause the transcription of gene silent and also peform a significant influence in the differentiation of Th17. Compared with healthy people, the H3K27me3 expression in PBMC of the AS patients is significantly reduced during disease activity. Moreover, H3K27me3 expression was significantly negatively correlated with the Th17 differentiation characteristic transcription factor RORγt. This indicates that H3K27me3 may become a viral epigenetic modification of the AS, the changes in H3K27me3 methylation levels may also contribute to the occurrence, development, and the inflammation of AS (Chen et al., 2024).

3 AS involving B cells

Due to the lack or yet to be discovered of clear autoantibodies related to AS, there are currently few studies on how the B cells involve in the mechanism of AS. But there are already many clues indicating that B cells take part in the appearance and development of AS. One important clue is that many genes expressed by B cells have been found to be affected in AS patients. For example, MHC class II genes that have limited expression on nucleated cells and are also expressed by B cells are associated with AS patients, are associated with several other HLA-genes and are not affected by HLA-B27. Variations in the BACH2 gene, which encodes a very effective transcriptional regulator of B cells, have also been found in AS patients. The presence of TBX21 gene was significantly associated with AS. Variants of IL-10 coding genes, a cytokine that regulates immune responses and is developed via regulatory T cells and B cells, are also associated with AS (Soltani et al., 2024).

compartment is disrupted. B cells have a significant function in the causes of many chronic immune-mediated diseases and exhibit dysregulated scattering involved in the subsets of peripheral B cell compartment. The first is that total B cells showed a higher frequency when considering how active the AS was at a given time. In addition, the abilities of AS patients’ regulatory B cells to produce IL-10 may also reduce to some degree. B cell activation usually have something to do with higher expression of CD86, CD38, and CD95. Studies have found that in AS patients (Wilbrink et al., 2021), B cells express high levels of CD86 and CD95; the frequency of CD38-expressing plasma cells is higher, proving that the activation of B cells and plasma cells is increased in AS patients (Soltani et al., 2024).

In addition, although B cell antibodies involved in AS are not clearly defined, an increasing number of studies indicate the existence of specific or autoantibodies in AS patients. One type is autoantibodies that react against intracellular antigens. Typical examples include Nuclear antibodies (ANAs), Antineutrophil cytoplasmic antibodies (ANCA), Prefoldin subunit 5 and Beta-2 microglobulin produced against Nuclear antigens, Cytoplasmic molecules, Chaperone proteins respectively. The other is a corresponding antibody produced against the metabolic process of bone repair (Soltani et al., 2024). Some part of AS patients show the situations of autoantibodies to OPG.

studies have also found B lymphatic infiltration in the spinal cord, fibrous tissue, hip synovium, peripheral joints and other parts.

To sum up, in AS patients, there are variations in B cell expression genes and imbalances in different cytokines, which affect the effects and growth of the cells. B cells express more CD86 and CD95, and peripheral blood B cells are disordered and imbalanced. Some autoantibodies are also found in AS patients, antibodies targeting bone repair and microbial antigens. B cells exist in typical AS inflammatory sites such as the spine and peripheral joints. These all indicate that immune disorders involving B cells are likely to lead to the occurrence of AS.

4 Changes in immunoglobulins

Normally, patients with AS have weak immune responses and weak delayed-type hypersensitivity reactions. Studies have found that the average patient lacks anti-IgG antibodies in the serum, but when the disease is active, serum IgG, IgA, and IgM levels show an increase.

5 Conclusion

In conclusion, although the pathogenesis of AS is still unclear, a review of the latest literature and experimental studies found that immune disorders are an important factor causing AS. The mainstream hypothesis is that inflammation and T cell-mediated immune responses greatly affect AS, but immune disorders caused by B cells are also likely to contribute to the onset of AS. With the mediation of T cells and B cells, immunoglobulins also change, further causing inflammatory reactions and so on. I firmly believe that in the future, as research continues to deepen, we will be able to clarify the pathogenesis of AS. For AS caused by different causes of immune disorders, targeted therapeutic drugs can be developed to improve the inflammatory response, relieve AS symptoms, and enhance patients' quality of life.

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