Lymphozytensubpopulationen als Surrogatmarker bei antiretroviraler Therapie

Bogner, Johannes R.; Goebel, Frank-Detlef

doi:10.1007/bf01644477

Cited by 10 publications

(4 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Though immune “activation” markers have not been clearly defined for the gut, we measured CD38 and HLA-DR because these markers have been used to distinguish activated T cells in the peripheral blood and have been extensively correlated with poor prognosis [20–31]. T-cell activation was higher in all four gut sites compared to blood (Figure 5).…”

Section: Resultsmentioning

confidence: 99%

Differences in HIV Burden and Immune Activation within the Gut of HIV‐Positive Patients Receiving Suppressive Antiretroviral Therapy

et al. 2010

View full text Add to dashboard Cite

Background The gut is a major reservoir for HIV in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV. Methods In 8 HIV-1+ adults on ART with CD4>200 and plasma VL<40, levels of HIV and T-cell activation were measured in blood and endoscopic biopsies from the duodenum, ileum, right colon, and rectum. Results HIV DNA and RNA per CD4+T-cell were higher in all four gut sites compared to blood. HIV DNA increased from the duodenum to the rectum, while the median HIV RNA peaked in the ileum. HIV DNA correlated positively with T-cell activation in the PBMC but negatively with T-cell activation in the gut. Multiply-spliced RNA was infrequently detected in gut, and unspliced RNA/DNA ratios were lower in the colon and rectum relative to PBMC, reflecting paradoxically low HIV transcription given the higher T-cell activation in the gut. Conclusions HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA and T-cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut.

show abstract

Section: Resultsmentioning

confidence: 99%

Differences in HIV Burden and Immune Activation within the Gut of HIV‐Positive Patients Receiving Suppressive Antiretroviral Therapy

et al. 2010

View full text Add to dashboard Cite

show abstract

“…It is well established that elevated CD3 and CD4 counts and higher CD4/CD8 ratio are associated with better prognosis in patients with HIV [13]. For this reason Dzherelo is likely to influence positively the outcome of treatment and disease progression in our study population.…”

Section: Discussionmentioning

confidence: 87%

Effect of Immunomodulating Adjuvant Dzherelo (Immunoxel) in HIV Infected Patients Receiving Standard Antiretroviral Therapy

Nikolaeva¹,

Maystat²,

Volyanskii³

et al. 2009

TOVJ

View full text Add to dashboard Cite

Open-label, matched-case, comparative trial was conducted in 40 HIV-infected patients to evaluate the adjunct effect of Dzherelo (Immunoxel) on immune and viral parameters. Arm A (n=20) received anti-retroviral therapy (ART) consisting of zidovudine, lamivudine, and efavirenz and arm B (n=20) received ART with Dzherelo. After 2 months total T-lymphocytes increased in ART recipients from 664 to 819 cells/μl (P=0.06), whereas in Dzherelo recipients they rose from 595 to 785(P=0.03). The CD4 T-cells expanded by 57.3% (218 to 343; P=0.002) in the ART arm and by 93.5% (184 to 356; P=0.004) in the Dzherelo arm. The accrual in absolute and relative number of CD8+ lymphocytes in ART and in the Dzherelo recipients was 43.2% (2.7%) and 50.4% (-0.5%) respectively. The CD4/CD8 ratio in Dzherelo recipients increased from 1.495 to 1.940 (P=0.03) but insignificant in the control: 1.418 to 1.613 (P=0.14). Activated CD3+ HLADR+ T-cells increased from 209 to 264 (P=0.02) and from 161 to 348 (P=0.0007) in ART and Dzherelo recipients respectively. No changes in CD20+ B-lymphocytes were seen in the control, but in Dzherelo patients they declined from 509 to 333 (P=0.00008). The proportion of CD3- CD16+CD56+ NK cells was not affected by ART but addition of Dzherelo raised NK cells from 11.2% to 17.1% (P=0.0001). About three-quarters (14/19) of patients on ART displayed decrease in viral load (1718 to 1419 copies/ml; P=0.008), while 95% of patients on Dzherelo had a decrease (1793 to 1368; P=0.001). Dzherelo has a favorable effect on the immune status and viral burden when given as an immunomodulating adjunct to ART.

show abstract

“…Changes in the counts of specific lymphocyte subsets have been previously evaluated as surrogate markers of efficacy in antiretroviral therapy [ 39 ], are important as a pharmacodynamic marker for ozanimod, and provide a better understanding of the mechanism of action of ozanimod. Dysregulation of immune response plays a critical role in the pathogenesis of IBD, and B cells are among the immune cell types that are involved in intestinal inflammation [ 3 , 6 ].…”

Section: Discussionmentioning

confidence: 99%

Ozanimod Differentially Impacts Circulating Lymphocyte Subsets in Patients with Moderately to Severely Active Crohn’s Disease

Harris,

Feagan,

Hanauer

et al. 2024

Dig Dis Sci

View full text Add to dashboard Cite

Background Ozanimod showed efficacy and safety in the phase 2 STEPSTONE study conducted in patients with moderately to severely active Crohn’s disease. Aims This analysis assessed the effects of ozanimod on circulating lymphocytes in Crohn’s disease. Methods Patients received ozanimod 0.92 mg for 12 weeks. Lymphocyte subtypes were evaluated using multicolor flow analysis on blood samples collected before treatment and on Week 12. Absolute lymphocyte count changes were analyzed by Wilcoxon signed rank tests. Disease activity changes and efficacy outcomes were evaluated at Week 12, and associations with lymphocyte subtype levels were assessed using Spearman’s correlation and logistic regression. Results Reductions in median total T, Th, and cytotoxic T cells occurred at Week 12 (45.4%–76.8%), with reductions in most subtypes of 47.5% to 91.3% ( P < 0.001). CD8 + terminally differentiated effector memory cells were largely unaffected (median change, − 19%; P = 0.44). Reductions in median total B cells occurred at Week 12 (76.7%), with reductions in subtypes of 71.4% to 81.7% ( P < 0.001). Natural killer and monocyte cell counts were unchanged. Greater baseline levels and changes in nonswitched memory B cells were significantly associated with clinical, endoscopic, and histologic efficacy ( P < 0.05, all comparisons). Conclusions Ozanimod reduced circulating levels of all B-cell and most T-cell subsets but not monocytes or natural killer cells. Key subsets relevant to immune surveillance were not reduced, supporting the low risk of infection and malignancy with ozanimod in chronic inflammatory diseases. Levels of nonswitched memory B cells were associated with efficacy, providing a potential marker for ozanimod response. Trial Registration ClinicalTrials.gov: NCT02531113, EudraCT: 2015–002025–19 Graphical Abstract Supplementary Information The online version contains supplementary material available 10.1007/s10620-024-08391-z.

show abstract

Lymphozytensubpopulationen als Surrogatmarker bei antiretroviraler Therapie

Cited by 10 publications

References 19 publications

Differences in HIV Burden and Immune Activation within the Gut of HIV‐Positive Patients Receiving Suppressive Antiretroviral Therapy

Differences in HIV Burden and Immune Activation within the Gut of HIV‐Positive Patients Receiving Suppressive Antiretroviral Therapy

Effect of Immunomodulating Adjuvant Dzherelo (Immunoxel) in HIV Infected Patients Receiving Standard Antiretroviral Therapy

Ozanimod Differentially Impacts Circulating Lymphocyte Subsets in Patients with Moderately to Severely Active Crohn’s Disease

Contact Info

Product

Resources

About