Alteration of liver‐infiltrated and peripheral blood double‐negative T‐cells in primary biliary cholangitis

Li, Shuxiang; Lv, Tingting; Zhang, Chunpan; Wang, Tianqi; Tian, Dan; Sun, Guan; Wang, Yan; Zhao, Xinyan; Duan, Weijia; Chen, Sha; Li, Min; Ma, Hong; Kong, Yuanyuan; You, Hong; Ou, Xiaojuan; Chen, Guangyong; Su, Jianrong; Zhang, Dong; Jia, Jidong

doi:10.1111/liv.14136

Cited by 12 publications

(8 citation statements)

References 37 publications

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“…This finding suggests that dysfunction of the Treg cells may reduce immune tolerance and confer effector lymphocytes to damage the BEC. Besides, myeloid-derived suppressor cells [ 35 ], double-negative T cells (DNT) [ 36 ], and mucosal-associated invariant T cell (MAIT) [ 37 ] were also implicated in the development of PBC. However, the exact roles of these cells are still not fully elucidated.…”

Section: Pathogenesismentioning

confidence: 99%

APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis

You

Efe

et al. 2022

Hepatol Int

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Section: Pathogenesismentioning

confidence: 99%

APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis

You

Efe

et al. 2022

Hepatol Int

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“…[ 32 ]. Within 24 h after kidney ischemia-reperfusion injury (IRI), kidney DNT cells expanded significantly and suppressed the proliferation of activated CD4 + T cells [ 32 , 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Expansion of Double-Negative T Cells in Patients before Liver Transplantation Correlates with Post-Transplant Infections

Lei

Tian

Zhang

et al. 2022

JCM

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Liver transplantation (LTx) is currently the only effective therapy for patients with end-stage liver diseases, but post-transplant infection is a key issue for morbidity and mortality. In this study, we found that pre-transplant patients with an expansion of double-negative T (DNT) cells (CD3+CD4−CD8− T cells) had an increased incidence of infections within the first 6 months after LTx. These DNT cells also negatively correlated with their CD4/CD8 ratio. Compared to patients who had no infections after LTx, these DNT cells expressed more CD25, especially in the memory compartment. The receiver operating characteristic (ROC) analysis showed that the threshold area under the ROC curve of DNT cells which could be used to distinguish LTx patients with post-transplant infections from patients without infections after LTx was 0.8353 (95% CI: 0.6591–1.000). The cut-off for the pre-LTx DNT cell level was 11.35%. Although patients with post-transplant infections had decreased levels of CD4/CD8 T cells, CD8+ T cells in these patients were more exhausted, with higher PD-1 expression and lower IFNγ secretion. The increased levels of DNT cells in patients with post-transplant infections were still observed 2 weeks after LTx, with higher proportions of memory DNT cells. In conclusion, increased levels of DNT cells in pre-LTx patients may be valuable for the prognosis of post-transplant infections, especially within the first 6 months after LTx.

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“…According to our knowledge, there is only one report stating that PBMCs with 5-day stimulation with Staphylococcus aureus Cowan I (SAC-I) and the addition of hydrophobic bile acids (chenodeoxycholic acid, CDCA; ursodeoxycholic acid, UDCA) may strongly depress IgM production but not IgA or IgG in vitro culture (45). Metabolites of bile acids regulate the balance of Treg cells and Th17 cells in intestinal inflammation (34) and reduce both humoral and cellular immunity in patients with primary biliary cholangitis (PBC) (46)(47)(48), however, the modulatory roles of bile acids in vaccination responses either in adults or children have not been reported so far. Our ongoing projects is trying to delineate the potential mechanism of bile acids in reducing humoral immunity in children with BA.…”

Section: Discussionmentioning

confidence: 99%

Bile Acids Impair Vaccine Response in Children With Biliary Atresia

Liu

et al. 2021

Front. Immunol.

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BackgroundVaccination is the best way to protect children under 5 years from death or disability. Children with biliary atresia (BA), which is the most common pediatric cholestatic end-stage liver disease (PELD), are more vulnerable to infectious diseases. However, the vaccination coverage and factors modulating vaccine responses in children with BA are largely unknown.MethodsIn this study, 288 children (median age: 7 months) diagnosed with BA before liver transplantation were enrolled for the evaluation of vaccination status and the factors affecting the immune response to the hepatitis B (HBV) vaccine. Moreover, 49 BA children (median age: 4 months) were enrolled for flow cytometric analysis of CD4+ T cells and CD19+ B cell subsets and correlations with serum bile acid levels.ResultsGenerally, these children had very low routine vaccination rates for the meningococcal serogroup AC (Men AC) (41.2%), measles-mumps-rubella (MMR) (31.3%), poliomyelitis (Polio) (25.3%), hepatitis A (HAV) (25.0%), Japanese encephalitis (JE) (15.0%), diphtheria-tetanus-pertussis (DTP) (14.2%), meningococcal serogroup A (Men A) (13.5%) and varicella (VAR) (10.8%) vaccines, but not for the HBV (96.2%) and bacillus Calmette-Guérin (BCG) (84.7%) vaccines. Remarkably, 19.8% (57/288) of the patients had HBV infection. Out of 220 patients vaccinated for HBV, 113 (51.4%), 85 (38.6%) and 22 (10%) had one, two or three doses of the HBV vaccine, respectively. Furthermore, logistic regression analysis revealed that the bile acid level was an independent factor associated with poor HBV vaccine response (p = 0.03; OR = 0.394; 95% CI = 0.170-0.969). Immunophenotyping showed that bile acids were only negatively correlated with the CD19+CD27+IgG+ post-class-switched memory B cell ratio (p = 0.01).ConclusionThis study reveals the overall vaccination rates of routine vaccines in Chinese BA children are very low and the poor HBV vaccine responses are associated with bile acids, possibly via the inhibition of CD19+CD27+IgG+ post-class-switched memory B cell response.Clinical Trial Registrationhttp://www.chictr.org.cn, identifier ChiCTR1800019165.

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Alteration of liver‐infiltrated and peripheral blood double‐negative T‐cells in primary biliary cholangitis

Cited by 12 publications

References 37 publications

APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis

APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis

Expansion of Double-Negative T Cells in Patients before Liver Transplantation Correlates with Post-Transplant Infections

Bile Acids Impair Vaccine Response in Children With Biliary Atresia

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