Effective long-term solution to therapeutic remission in Inflammatory Bowel Disease: Role of Azathioprine

Adam, Lyla; Phulukdaree, Alisa; Soma, Prashilla

doi:10.1016/j.biopha.2018.01.152

Cited by 19 publications

(17 citation statements)

References 86 publications

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“…All 4 of these DMARDs have both immunosuppressive and anti-microbial properties [46]. AZA is an immunosuppressant agent widely used in the management of inflammatory bowel diseases (IBD) and uveitis [47, 48]. AZA is metabolized in the liver to its active form 6-mercaptopurine, which inhibits maturation of B and T lymphocytes through its activity as an antagonist of purine metabolism, resulting in the inhibition of DNA, RNA, and consequently protein synthesis.…”

Section: Correlation Between the Gut Microbiome And Autoimmune Uveitismentioning

confidence: 99%

The Role of Gut Microbiome in Autoimmune Uveitis

Chen

2020

Ophthalmic Res

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The gut microbiome has important physiological functions and plays an indispensable role in the human body. Currently, there are an increasing number of studies revealing the close correlation between dysbiosis of the gut microbiome and a variety of autoimmune diseases, including autoimmune uveitis. This brief review summarizes recent literature regarding the relationship between dysbiosis and the occurrence and development of autoimmune uveitis. Dysbiosis participates in the pathogenesis of autoimmune uveitis largely by 4 mechanisms: antigenic mimicry, disturbance of intestinal immune homeostasis, destruction of the intestinal barrier, and reduction of beneficial anti-inflammatory metabolites. Further elucidation of these mechanisms will facilitate the treatment of the gut-microbiome-relevant autoimmune diseases by potential therapeutic strategies, such as antibiotics, probiotics, diet modifications, and fecal microbial transplantation.

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Section: Correlation Between the Gut Microbiome And Autoimmune Uveitismentioning

confidence: 99%

The Role of Gut Microbiome in Autoimmune Uveitis

Chen

2020

Ophthalmic Res

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“…Given the rate of hospitalization, the cost of medication and treatment caused by AZA cytotoxicity, the high prices of genetic testing are worthwhile. [ 5 ]…”

Section: Discussionmentioning

confidence: 99%

Azathioprine-induced toxoplasma gondii infection in a patient with Crohn's disease with NUDT15 variation

Tan

Da-lian

et al. 2021

Medicine

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Introduction: Azathioprine (AZA) has been widely used for the treatment of various immune-related diseases and has become a mainstay in the treatment of inflammatory bowel disease. However, patients with genetic mutations may experience severe adverse events when treated with azathioprine. Most of the previous literature focused on the TPMP gene-related adverse reactions, herein, we report a case of Crohn's disease patient with nucleoside diphosphate-linked moiety X motif 15 gene (NUDT15) variation and wild-type TPMP gene who developed toxoplasma gondii infection after azathioprine treatment. Patient concerns: A 56-year-old Crohn's disease patient developed toxoplasma gondii infection within 2 months after the administration of azathioprine; however, he had no relevant high-risk factors. Diagnosis: Subsequent genetic testing revealed that the patient was heterozygous for NUDT15. Therefore, it was reasonable to consider that the patient's genetic mutation resulted in reduced tolerance to azathioprine, leading to low immunity and eventually toxoplasma infection. Interventions: AZA was then discontinued; after anti-infection, antipyretic and other supportive treatments were administered, the patient's condition gradually improved. Outcomes: The patient was followed up at 1, 3, and 6 months after discharge; fortunately, he was in good health. Conclusion: We report a case of Crohn's disease in a patient who developed severe pneumonia caused by toxoplasma gondii infection due to the administration of AZA, with normal TPMP gene but NUDT15 gene mutation. This indicates that NUDT15 variation may contribute to severe adverse events in patients treated with azathioprine, and we suggest that NUDT15 genotype be detected before the use of azathioprine in order to provide personalized therapy and reduce side effects.

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“…Although the role of azathioprine monotherapy in IBD for the maintenance of remission is still a point of discussion among clinicians, AZA remains an affordable and viable option for the public sector. However, genetic screening for the presence of SNP on the TPMT gene of patients with IBD is necessary to ensure therapeutic efficacy [ 62 ]. The mutations in the TPMT gene cause a TPMT deficiency, which is a reduction in the activity of the TPMT enzyme.…”

Section: Discussionmentioning

confidence: 99%

Thiopurine Drugs in the Treatment of Ulcerative Colitis: Identification of a Novel Deleterious Mutation in TPMT

Harmand

Solassol

2020

Genes

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Chronic inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis. Both are characterized by inflammation of part of the digestive tract lining. Azathioprine (AZA) is a well-known immunosuppressant that has been known for many years for its ability to provide long-term disease remission in IBDs, but has important side effects, most of which are related to a single nucleotide polymorphism in the gene for thiopurine methyltransferase (TPMT), which ensures the degradation and efficacy of AZA. Since a direct correlation between TPMT gene polymorphisms and the haematological toxicity of the AZA treatment has been widely demonstrated, TPMT genotyping has been made necessary prior to any introduction of AZA. The monitoring of thiopurine metabolites presents one of the factors that limit wide adaptation of these thiopurines in clinical practice. Thus, identifying patients with asymmetric metabolism could help clinicians provide an ideal treatment recommendation to improve response and reduce adverse effects. Here, we review the role of AZA in the treatment of IBD and discuss the usefulness of TPMT genotyping to guide clinical decision-making. In addition, we report the identification of a new molecular alteration, never described, TPMT mutation affecting the TPMT activity and responsible for deleterious side effects in a clinical case of a 20-year-old woman patient.

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Effective long-term solution to therapeutic remission in Inflammatory Bowel Disease: Role of Azathioprine

Cited by 19 publications

References 86 publications

The Role of Gut Microbiome in Autoimmune Uveitis

The Role of Gut Microbiome in Autoimmune Uveitis

Azathioprine-induced toxoplasma gondii infection in a patient with Crohn's disease with NUDT15 variation

Thiopurine Drugs in the Treatment of Ulcerative Colitis: Identification of a Novel Deleterious Mutation in TPMT

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