Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
The management of immunosuppressive therapies is challenging, as physicians are confronted with difficulties to keep the balance between immunosuppression on one hand and raised risk of infection on the other hand. Currently, there is no standardized immune monitoring established helping to guide immunosuppression. Therefore, CMV-specific T cell responses were analyzed before and after initiation of immunosuppression in patients with newly diagnosed rheumatic diseases to assess the immune network in a functional fashion.
Methods:
PBMC were isolated from treatment naive patients and at different time points following initiation of immunosuppression using a ficoll-separation protocol, and stimulated utilizing a novel urea-activated-CMV-tegument phosphoprotein 65 (pp65, T-Track® CMV, Lophius Biosciences, Germany). Protein specific T cell responses were analyzed and quantitated by ELISPOT detecting IFN-γ secreting cells. In addition, FACS-analyses have been performed simultaneously to observe phenotypic changes in PBMC subpopulations utilizing characteristic surface markers.
Results:
23 treatment naive patients suffering from newly diagnosed rheumatic diseases were included in this study (RA: 11, PMR: 7, SpA: 3, connective tissue diseases: 3). In total, 14 of the 23 patients (60,8%) had a positive IgG-CMV-serology and were further analyzed. A CMVpp65-specific T cell response could be observed in 5 of these 14 CMV-positive patients (35,7%) allowing for monitoring of the T cell function. There was a decrease of more than 80% of IFN-γ secreting cells 8-19 days (mean 10,6; SD ± 4,7) following initiation of immunosuppression (cumulative glucocorticoid dosage median: 405 mg) in 4 (80%) of these patients demonstrating substantial impairment of the specific immune response leading to a diminished T cell function. In contrast, no or only a minimal decrease in IFN-γ secreting cells could be observed in 1 (20%) patient despite immunosuppressive therapy. Phenotypic analyses revealed an increase (mean +26%) of the effector-memory CD4+-T-cell population in all patients, as well as a rise (mean +22%) of the central memory CD4+-T-cells. Moreover, there was a decrease of CD8+-T cells (mean -23,7%) as well as NK cells (mean –46%), whereas a substantial increase (mean +70%) could be observed in the memory B-cell subpopulation. From the CMV-positive patients, 8 could be followed-up. Clinically relevant infections occurred in 3 patients. 2 of these patients presented with an impaired pp65 specific T cell response already before initiation of immunosuppression, whereas a dramatic decrease of -86% in IFN-γ secreting cells could be observed in one patient 12 weeks following initiation of immunosuppression, who developed a respiratory infection.
Conclusion:
The present results demonstrate a substantially impaired function of the specific immune system in a subgroup of patients following initiation of immunosuppression. We propose that these patients have a higher risk for infection and that utilization of the novel Elispot-assay based on urea-activated CMV-pp65 has the potential to guide immunosuppression as a valuable tool for functional immunmonitoring.
Disclosure:
E. Le Bras,
None;
S. Weigand,
None;
L. Deml,
Lophuis GmbH,
1;
D. Halbritter,
None;
B. P. Ehrenstein,
None;
W. Hartung,
None;
M. Fleck,
Lophius GmbH,
1.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/assessment-of-cytomegalovirus-specific-t-cell-responses-upon-initiation-of-immunosuppression-in-patients-suffering-from-rheumatic-diseases-as-novel-approach-for-functional-immune-monitoring/