Most Read Articles
Elvira Manzano, 6 days ago
Bisphosphonates have proven antifracture efficacy and remain to be the cornerstone of osteoporosis treatment. However, a drug holiday is of particular importance with bisphosphonates due to some signals with long-term use of the drug, including rare incidence of atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ), says a leading endocrinologist at AFOS 2017.
Yesterday
Drinking coffee, whether caffeinated or decaffeinated, is associated with a reduced risk of cardiovascular disease (CVD) and ischaemic heart disease (IHD) mortality in patients with a prior myocardial infarction (MI), according to a recent study.
3 days ago
Breast cancer patients have notably different microbiomes in the local breast tissue and urinary tract, a recent study reveals. Particularly, species in the Methylobacterium genus are reduced in the local breast tissue while the urinary tract is enriched in gram-positive bacteria.
Pearl Toh, 13 Oct 2017
Women with higher plasma tryptophan concentrations were less likely to have poor sleep quality during pregnancy, especially among those with anxiety symptoms, according to the GUSTO* study.

Regulatory T cells, IL-2 greatly reduced during pAIH treatment

Tristan Manalac
14 Jul 2017

Intrahepatic regulatory T cells (Tregs), enriched in untreated paediatric autoimmune hepatitis (pAIH) patients, are disproportionately reduced during treatment, a new study reveals. Similarly, serum concentrations of interleukin (IL)-2 also decrease during treatment.

“Until the start of this study there was no systematic analysis of intrahepatic Treg numbers available, neither before nor under ongoing therapy in pAIH,” said researchers. “Thus, we retrospectively immunophenotyped the intrahepatic T and B cell compartment, including Treg in pAIH in the initial diagnosis and in the follow-up during therapy.”

The infiltration density of CD4+ + CD8+ cells were significantly greater in untreated pAIH (3,373 cells/mm2) than in treated pAIH patients (2,065 cells/mm2; p=0.003). CD79+ cells were also significantly greater in untreated (1,135 cells/mm2) than in treated (710 cells/mm2; p=0.03) pAIH patients. [PLoS One 2017;doi:10.1371/journal.pone.0181107]

CD4+ FOXP3+ density (p<0.001), CD4+ FOXP3+ / CD79+ ratio (p=0.004) and CD4+ FOXP3+ / CD4+ + CD8+ ratio (p<0.001) were significantly reduced in treated than in untreated pAIH patients. Of these, portal levels of CD4+ FOXP3+ T-cells showed the largest decline (146 to 63 cells/mm2), resulting in a subsequent significant decline in CD4+ FOXP3+ to CD4+ and CD8+ ratio (0.044 to 0.021).

Declines in Treg levels during treatment may be explained in part by the steroid and azathioprine nature of immunosuppressive therapy, according to researchers. Another explanation may be the insufficient regulation of Tregs in the liver in response to the shortage of IL-2 during therapy.

“Additionally, chemokines like CXCL10 (IP-10) that are involved in Treg homing into the liver are significantly downregulated under ongoing therapy in pAIH. Thus, a reduced hepatic recruitment of Treg could contribute to the Treg decline under therapy as well,” researchers said.

A comparison of the concentrations of 28 serum cytokines between treated and untreated pAIH patients showed that 11 were significantly reduced during treatment. These were IL-2, IL-6, IL-8, IL-9, IL-15, IL-17, FGFβ, IP-10, MIP-1a, MIP-1b and HGF.

While most of these cytokines showed two- to fivefold reductions in serum levels, IL-2, which had the greatest decline during treatment, showed a reduction of around tenfold. Moreover, IL-2 levels were significantly higher in untreated pAIH patients than in untreated adult AIH (aAIH) patients (p<0.05).

“[T]he strong reduction of the serum IL-2 and 10 other cytokines observed here go simultaneously to a contraction of the intrahepatic T cell pool, the main intrahepatic IL-2 source, as expressed by declining T cell densities within the shrinking infiltrates under therapy in pAIH and aAIH. This may contribute to the disproportionate decline of intrahepatic Treg,” researchers explained.

The study included 53 paediatric patients (40 untreated, 13 under therapy) with confirmed AIH; 12 paediatric nonalcoholic fatty liver disease patients were included as liver histology controls, while 34 age- and gender-matched healthy paediatric controls were included for blood cytokine assessment.

“The disproportional decline of intrahepatic Treg during ongoing therapy is consistent in pAIH and aAIH and may result from a decrease of the Treg survival factor IL-2. Such associations are relevant for the design and evaluation of novel approaches for second line therapies or the withdrawal of the immunosuppressive therapies,” researchers concluded.

Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Hepatology - Malaysia digital copy today!
DOWNLOAD
Editor's Recommendations
Most Read Articles
Elvira Manzano, 6 days ago
Bisphosphonates have proven antifracture efficacy and remain to be the cornerstone of osteoporosis treatment. However, a drug holiday is of particular importance with bisphosphonates due to some signals with long-term use of the drug, including rare incidence of atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ), says a leading endocrinologist at AFOS 2017.
Yesterday
Drinking coffee, whether caffeinated or decaffeinated, is associated with a reduced risk of cardiovascular disease (CVD) and ischaemic heart disease (IHD) mortality in patients with a prior myocardial infarction (MI), according to a recent study.
3 days ago
Breast cancer patients have notably different microbiomes in the local breast tissue and urinary tract, a recent study reveals. Particularly, species in the Methylobacterium genus are reduced in the local breast tissue while the urinary tract is enriched in gram-positive bacteria.
Pearl Toh, 13 Oct 2017
Women with higher plasma tryptophan concentrations were less likely to have poor sleep quality during pregnancy, especially among those with anxiety symptoms, according to the GUSTO* study.