Association of MICA Alleles and Human Leukocyte Antigen B in Turkish Patients Diagnosed With Behçet's Disease

Eyerci, Nilnur; Balkan, Eda; Akdeniz, Necmettın; Keleş, Sadullah

doi:10.5606/archrheumatol.2018.6704

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…Activating receptors KIR2DS1 and KIR2DS2 are implicated in the pathogenesis of autoimmune diseases such as in the examples of RA and psoriasis (332,333). The expression of the ligands of the activating receptors, such as MICA also contributes to the disease pathogenesis such that alternated receptor affinty may lead to activaiton in predisposed individuals, observed in various autoimmune diseases including RA, BD and type 1 diabetes (334)(335)(336). Finally, certain KIR/HLA combinations reduce the activation threshold of the NK cells and can be protective against some infections, while the same KIR/HLA combination may also predispose autoimmunity.…”

Section: Discussionmentioning

confidence: 99%

The Role of Natural Killer Cells in Autoimmune Diseases

et al. 2021

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Natural killer (NK) cells, the large granular lymphocytes differentiated from the common lymphoid progenitors, were discovered in early 1970’s. They are members of innate immunity and were initially defined by their strong cytotoxicity against virus-infected cells and by their important effector functions in anti-tumoral immune responses. Nowadays, NK cells are classified among the recently discovered innate lymphoid cell subsets and have capacity to influence both innate and adaptive immune responses. Therefore, they can be considered as innate immune cells that stands between the innate and adaptive arms of immunity. NK cells don’t express T or B cell receptors and are recognized by absence of CD3. There are two major subgroups of NK cells according to their differential expression of CD16 and CD56. While CD16+CD56dim subset is best-known by their cytotoxic functions, CD16-CD56bright NK cell subset produces a bunch of cytokines comparable to CD4+ T helper cell subsets. Another subset of NK cells with production of interleukin (IL)-10 was named as NK regulatory cells, which has suppressive properties and could take part in immune-regulatory responses. Activation of NK cells is determined by a delicate balance of cell-surface receptors that have either activating or inhibitory properties. On the other hand, a variety of cytokines including IL-2, IL-12, IL-15, and IL-18 influence NK cell activity. NK-derived cytokines and their cytotoxic functions through induction of apoptosis take part in regulation of the immune responses and could contribute to the pathogenesis of many immune mediated diseases including ankylosing spondylitis, Behçet’s disease, multiple sclerosis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus and type-1 diabetes. Dysregulation of NK cells in autoimmune disorders may occur through multiple mechanisms. Thanks to the rapid developments in biotechnology, progressive research in immunology enables better characterization of cells and their delicate roles in the complex network of immunity. As NK cells stand in between innate and adaptive arms of immunity and “bridge” them, their contribution in inflammation and immune regulation deserves intense investigations. Better understanding of NK-cell biology and their contribution in both exacerbation and regulation of inflammatory disorders is a requisite for possible utilization of these multi-faceted cells in novel therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

The Role of Natural Killer Cells in Autoimmune Diseases

et al. 2021

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“…On the other hand, Eyerci et al reported the MICA*006 (MICA-A6) and MICA*009 alleles were associated with BD susceptibility in the HLA-B*51 positive Turkish population. [30]. MICA-A5.1 was indicated a negative correlation with ocular lesions and iridocyclitis in BD patients [31].…”

Section: Micamentioning

confidence: 87%

Genetics of Behçet’s Disease

Kocaaga¹

2023

Rare Diseases - Recent Advances

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Behçet’s disease (BD; MIM 109650) is an autoinflammatory disease characterized by with recurrent oral aphthae, genital ulcers and vasculitis involving the skin, joints, eyes, veins, arteries, nervous and gastrointestinal systems. Although the pathogenesis remains uncertain, genome-wide and validation studies have demonstrated that genetic predisposition is a major factor in disease susceptibility. Several gene polymorphisms that are involved in the response to pathogens and modulate inflammation have been associated with the pathophysiology of BD. Understanding the genetic association with BD may ensure insight into the pathogenesis and for development of targeted therapies for this autoinflammatory disease. This chapter will deal the role of genetic and epigenetic factors as contributing factors in the pathogenesis of BD.

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“…MICA * 009 allele has also been found in a high frequency in melanoma patients compared with controls (51). Additionally, both MICA * 009 and MICA * 004 (MICA * A6) have been associated with Behcet disease (18,(52)(53)(54)(55)(56) and rheumatoid arthritis (57). However, this variant was less frequent in patients with colorectal cancer (58), indicating that MICA alleles play a different role depending on the type of cancer, possibly due to cellular and molecular mechanisms that are particularly associated with different types of tumors.…”

Section: Discussionmentioning

confidence: 99%

Major Histocompatibility Complex Class I-Related Chain A (MICA) Allelic Variants Associate With Susceptibility and Prognosis of Gastric Cancer

et al. 2021

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Gastric cancer (GC) is the fifth most prevalent type of cancer worldwide. Gastric tumor cells express MICA protein, a ligand to NKG2D receptor that triggers natural killer (NK) cells effector functions for early tumor elimination. MICA gene is highly polymorphic, thus originating alleles that encode protein variants with a controversial role in cancer. The main goal of this work was to study MICA gene polymorphisms and their relationship with the susceptibility and prognosis of GC. Fifty patients with GC and 50 healthy volunteers were included in this study. MICA alleles were identified using Sanger sequencing methods. The analysis of MICA gene sequence revealed 13 MICA sequences and 5 MICA-short tandem repeats (STR) alleles in the studied cohorts We identified MICA*002 (*A9) as the most frequent allele in both, patients and controls, followed by MICA*008 allele (*A5.1). MICA*009/049 allele was significantly associated with increased risk of GC (OR: 5.11 [95% CI: 1.39–18.74], p = 0.014). The analysis of MICA-STR alleles revealed a higher frequency of MICA*A5 in healthy individuals than GC patients (OR = 0.34 [95% CI: 0.12–0.98], p = 0.046). Survival analysis after gastrectomy showed that patients with MICA*002/002 or MICA*002/004 alleles had significantly higher survival rates than those patients bearing MICA*002/008 (p = 0.014) or MICA*002/009 (MICA*002/049) alleles (p = 0.040). The presence of threonine in the position MICA-181 (MICA*009/049 allele) was more frequent in GC patients than controls (p = 0.023). Molecular analysis of MICA-181 showed that the presence of threonine provides greater mobility to the protein than arginine in the same position (MICA*004), which could explain, at least in part, some immune evasion mechanisms developed by the tumor. In conclusion, our findings suggest that the study of MICA alleles is crucial to search for new therapeutic approaches and may be useful for the evaluation of risk and prognosis of GC and personalized therapy.

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Association of MICA Alleles and Human Leukocyte Antigen B in Turkish Patients Diagnosed With Behçet's Disease

Cited by 5 publications

References 21 publications

The Role of Natural Killer Cells in Autoimmune Diseases

The Role of Natural Killer Cells in Autoimmune Diseases

Genetics of Behçet’s Disease

Major Histocompatibility Complex Class I-Related Chain A (MICA) Allelic Variants Associate With Susceptibility and Prognosis of Gastric Cancer

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