Genetic risk factors for serious infections in inflammatory bowel diseases

Sasidharan, Saranya; Yajnik, Vijay; Khalili, Hamed; Garber, John J.; Xavier, Ramnik J.; Ananthakrishnan, Ashwin N.

doi:10.1080/00365521.2017.1286381

Cited by 6 publications

(8 citation statements)

References 48 publications

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“…[26] Individuals with IBD are at a higher risk of experiencing infectious complications, leading to increased hospitalizations and mortality rates. [26,27] Several disease-and treatment-related factors, such as aging, severity of illness, compromised barrier function of the in amed intestine, and impairment of immune dysfunction caused by malnutrition, contribute to the heightened susceptibility to infections in IBD patients. [27,28] Furthermore, the administration of steroids, immunomodulators, and biological agents for the treatment of IBD has been found to be associated with an elevated risk of serious infections and opportunistic infections.…”

Section: Discussionmentioning

confidence: 99%

“…[26,27] Several disease-and treatment-related factors, such as aging, severity of illness, compromised barrier function of the in amed intestine, and impairment of immune dysfunction caused by malnutrition, contribute to the heightened susceptibility to infections in IBD patients. [27,28] Furthermore, the administration of steroids, immunomodulators, and biological agents for the treatment of IBD has been found to be associated with an elevated risk of serious infections and opportunistic infections. [12,28,29] The occurrence of sepsis is a signi cant concern in the management of patients with IBD.…”

Section: Discussionmentioning

confidence: 99%

“…Potential clues may be discovered at the genetic level, as numerous crucial genes implicated in the pathogenesis of IBD and played pivotal roles in pathogen sensing and eliciting an appropriate immune response for their eradication. [27] Consequently, it has been hypothesized that polymorphisms within these genes could potentially impact immune responses. Against this backdrop, Sasidharan et al undertook a genetic analysis to unveil IBD-related immune response loci that could be associated with serious infections.…”

Section: Discussionmentioning

confidence: 99%

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Causal associations between autoimmune disease and sepsis: a two-sample Mendelian randomization study

Bai,

Zhuo,

Tong

et al. 2023

Preprint

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Background Recent observational studies have revealed an inconclusive correlation between autoimmune disease (AID) and sepsis, accompanied by an uncertain understanding of the causal relationship between the two. The objective of this study was to investigate the causality between AID and sepsis by employing a two-sample Mendelian randomization (MR) approach. Methods A genome-wide significant threshold (P < 5×10− 8) was achieved in order to identify single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for various common types of AID, such as Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Subsequently, the selected SNPs were assessed in relation to three categories of sepsis, namely sepsis, sepsis (critical care), and sepsis (28-day death in critical care). An inverse-variance weighted (IVW) estimation of MR was conducted, followed by sensitivity analysis on multiple dimensions. Results In the context of the study, a significant causal correlation was observed between genetic susceptibility and sepsis (28-day death in critical care) in patients with CD (OR, 1.246; 95% CI, 1.090–1.423; P = 0.0012). On the other hand, UC patients showed a slightly higher risk for sepsis, although this difference was not statistically significant (OR, 1.031; 95% CI, 0.988–1.064; P = 0.064). Additionally, there was evidence of a suggestive significant association between genetic liability to SLE (OR, 1.025; 95% CI, 1.009–1.043; P = 0.0029) and MS (OR, 1.038; 95% CI, 1.002–1.076; P = 0.041) with sepsis, but not specifically with sepsis (critical care) and sepsis (28-day death in critical care). However, there was no significant association of the genetic vulnerability to RA or AS with any of three types of sepsis. Conclusion Our study offers genetic evidence that supports a substantial causal relationship between CD and sepsis (28-day death in critical care), as well as a suggestive significant association between SLE/MS and sepsis. To enhance the specificity and objectivity of future research findings, it is recommended to specify the types of AID and the severity of sepsis. Furthermore, the identified genetic risk loci may serve as promising targets for drug development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Causal associations between autoimmune disease and sepsis: a two-sample Mendelian randomization study

Bai,

Zhuo,

Tong

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…We compared the internal factors, [ 11 ] including sex, age, course of disease, body mass index (BMI), Crohn disease activity index (CDAI), and family history of bowel diseases, between the complicated and control CD groups. The external factors [ 12 ] (mainly therapeutic factors) assessed included 5-aminosalicylic acid (5-ASA), immunosuppressants, steroids, probiotics, biological agents (BAs), and surgery after definite diagnosis.…”

Section: Methodsmentioning

confidence: 99%

Decreased CD8+CD28+/CD8+CD28– T cell ratio can sensitively predict poor outcome for patients with complicated Crohn disease

Dai

et al. 2017

Medicine

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Crohn disease (CD) with complications such as penetrating, stricturing, and perianal disease is called complicated CD. The aim of this study is to test the efficiency with which the CD8+CD28+/CD8+CD28– cell balance can predict a subsequent active stage in patients with newly diagnosed complicated CD.Seventeen patients with complicated CD and 48 CD patients with no complications were enrolled. Blood CD8+ T cells were tested from all of the 65 newly diagnosed CD patients upon enrollment. The potential risk factors were compared between the 2 groups. A 30-week follow-up was performed, and the efficiency of the CD8+ cell balance at predicting active CD was analyzed using receiver-operating characteristic curves. The cumulative remission lasting rates (CRLRs) were analyzed using the Kaplan–Meier method.Compared with the control CD group, patients with complicated CD were predominantly male and younger in age; they also had lower body mass indices (BMIs), higher Crohn disease activity indices (CDAIs), higher immunosuppressant and steroid prescription rates, and significantly higher surgical rates. The CD8+CD28+/CD8+CD28– balance was associated with BMI, CDAI, steroids, and surgery. The CD8+CD28+/CD8+CD28– ratios were significantly lower at week 0 and on the 6th, 22nd, and 30th week during follow-up with a shorter lasting time of remission for the complicated CD patients. The CD8+CD28+/CD8+CD28– ratio could accurately predict the active stage for the patients with complicated CD, and the highest sensitivity (89.2%) and specificity (85.3%) were found when the ratio was 1.03. Treatment with steroids and surgery, along with a significantly lower CD8+CD28+/CD8+CD28– ratio and lower CRLRs, was closely related to a worse outcome for the patients with complicated CD.Patients requiring steroids and surgery experience more severe disease activity and thus a disequilibrated immunological balance, which could be the main reason for a decreased CD8+CD28+/CD8+CD28– ratio. This ratio can sensitively predict the active stage for patients with complicated CD, and more care should be taken when this ratio is <1.03.

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“…46 Other risk factors specifically linked to increased infections in patients with IBD include diabetes, 47 nutritional status (body mass index < 17.5 kg/m 2 ) prior to surgery, 48 and the expression of specific genes. 49 TNF-α antagonists have also been linked to postoperative infections following bowel surgery in CD 50,51 and an overall increased risk of Clostridium difficile colitis. 52 Although combination therapy has been linked to increased infections in some studies, 45 this has been challenged by recent data.…”

Section: Risk Factors For Infectionmentioning

confidence: 99%

Biologic-Induced Infections in Inflammatory Bowel Disease: The TNF-α Antagonists

et al. 2018

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Genetic risk factors for serious infections in inflammatory bowel diseases

Cited by 6 publications

References 48 publications

Causal associations between autoimmune disease and sepsis: a two-sample Mendelian randomization study

Causal associations between autoimmune disease and sepsis: a two-sample Mendelian randomization study

Decreased CD8+CD28+/CD8+CD28– T cell ratio can sensitively predict poor outcome for patients with complicated Crohn disease

Biologic-Induced Infections in Inflammatory Bowel Disease: The TNF-α Antagonists

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