T Lymphocyte Subsets in Ulcerative Colitis

Официальное название

Peripheral Blood T Lymphocyte Subsets in Ulcerative Colitis

Обзор

1. Study the distribution of peripheral blood T lymphocyte subsets among ulcerative colitis patients. 2. Correlation of T-cell subsets to therapeutic response/ disease activity. 3. Assess the value of circulating IgG anti-Integrin αvβ6 in UC.

Подробное описание

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease of the large intestine, frequently involving the rectum, and characterized by chronic and recurrent mucosal inflammation and ulceration. Although its cause is not well understood, current evidence suggests innate and adaptive immunity play critical roles in its pathogenesis.

One of the main classes of immune cells that are affected by and contribute to UC is T cells. T-lymphocytes comprise a complex collection of highly differentiated T-cell subsets playing key roles in the regulation and the effector phase of the immune response. CD4+ T cells were found over-activated and proliferated in UC patients, which can induce disorders of the cytokine network and increase the occurrence of colitis.

Once intestinal pathogens or inflammatory mediators are not cleared in time, pro-inflammatory mononuclear phagocytes (MNPs) or polymorphonuclear leukocytes (PMNs) are often recruited to promote the polarization of naive CD4+ T cells into Th1, Th2, Th17, Treg and other subsets of cells.

The balances Th17/ Treg cells are important for maintaining intestinal homeostasis. Once the proportion Th17 cells increases, it often induces the production of pro-inflammatory cytokines that promote colonic inflammation, whereas Treg cells are usually secrete interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) for anti-inflammatory regulations.

UC-associated inflammation is also characterized by huge number of activated B cells and plasma cells, the latter being involved in the production of cytotoxic granules, immunoglobulins, and various autoantibodies, Recent studies have highlighted a novel autoantibody against integrin αvβ6 in the serum of patients diagnosed with UC.

Recently, targeting immune cells to inhibit inflammation has become a research hotspot. Biological therapies are highly effective hallmark therapies in UC. Despite their widespread use, the impact of these agents on the composition of the adaptive immune system is largely unexplored. Knowledge on such effects in UC could clarify the mechanism of action of these therapies, provide information about the status of the adaptive immune system, and could help finding cell-based markers.

Вмешательства

• Диагностический тест Flow cytometry
  flow cytometry to study distribution of T lymphocyte subsets in ulcerative colitis patients

Первичные конечные точки

• Study the distribution of T-cell subsets among ulcerative colitis patients. [Срок оценки: 3 years]
• Correlation of T-cell subtypes to therapeutic response [Срок оценки: 3 years]

Критерии участия

Критерии включения

• patients with clinical diagnosis of ulcerative colitis among both sexes.
• Age >18 years Old.

Критерии исключения

• Age <18 years old.
• Patients who refuse to participate in the study.
• Patients who have other autoimmune disease.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Adolph TE, Meyer M, Schwarzler J, Mayr L, Grabherr F, Tilg H. The metabolic nature of inflammatory bowel diseases. Nat Rev Gastroenterol Hepatol. 2022 Dec;19(12):753-767. doi: 10.1038/s41575-022-00658-y. Epub 2022 Jul 29. PMID 35906289
• Huang J, Wang F, Tang X. Uncovering the shared molecule and mechanism between ulcerative colitis and atherosclerosis: an integrative genomic analysis. Front Immunol. 2023 Aug 10;14:1219457. doi: 10.3389/fimmu.2023.1219457. eCollection 2023. PMID 37638002
• Fan Q, Dai W, Li M, Wang T, Li X, Deng Z, Li W, Li M. Inhibition of alpha2,6-sialyltransferase relieves symptoms of ulcerative colitis by regulating Th17 cells polarization. Int Immunopharmacol. 2023 Dec;125(Pt A):111130. doi: 10.1016/j.intimp.2023.111130. Epub 2023 Oct 26. PMID 37897948
• Hua Y, Liu R, Lu M, Guan X, Zhuang S, Tian Y, Zhang Z, Cui L. Juglone regulates gut microbiota and Th17/Treg balance in DSS-induced ulcerative colitis. Int Immunopharmacol. 2021 Aug;97:107683. doi: 10.1016/j.intimp.2021.107683. Epub 2021 Apr 26. PMID 33915494
• Yang W, Liu H, Xu L, Yu T, Zhao X, Yao S, Zhao Q, Barnes S, Cohn SM, Dann SM, Zhang H, Zuo X, Li Y, Cong Y. GPR120 Inhibits Colitis Through Regulation of CD4+ T Cell Interleukin 10 Production. Gastroenterology. 2022 Jan;162(1):150-165. doi: 10.1053/j.gastro.2021.09.018. Epub 2021 Sep 16. PMID 34536451
• Saez A, Gomez-Bris R, Herrero-Fernandez B, Mingorance C, Rius C, Gonzalez-Granado JM. Innate Lymphoid Cells in Intestinal Homeostasis and Inflammatory Bowel Disease. Int J Mol Sci. 2021 Jul 16;22(14):7618. doi: 10.3390/ijms22147618. PMID 34299236
• Marafini I, Laudisi F, Salvatori S, Lavigna D, Venuto C, Giannarelli D, Monteleone G. Diagnostic value of anti-integrin alphavbeta6 antibodies in ulcerative colitis. Dig Liver Dis. 2024 Jan;56(1):55-60. doi: 10.1016/j.dld.2023.06.024. Epub 2023 Jul 6. PMID 37407314
• Dulic S, Toldi G, Sava F, Kovacs L, Molnar T, Milassin A, Farkas K, Rutka M, Balog A. Specific T-Cell Subsets Can Predict the Efficacy of Anti-TNF Treatment in Inflammatory Bowel Diseases. Arch Immunol Ther Exp (Warsz). 2020 Apr 4;68(2):12. doi: 10.1007/s00005-020-00575-5. PMID 32248339

Идентификаторы

NCT: NCT06352515 · T cells in Ulcerative colitis

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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