Long-term survival after lung transplantation (LTx) is hampered by development of chronic lung allograft dysfunction (CLAD).
is an established risk factor for CLAD. Therefore, we investigated the ...effect of
eradication on CLAD-free and graft survival.Patients who underwent first LTx between July, 1991, and February, 2016, and were free from CLAD, were retrospectively classified according to
presence in respiratory samples between September, 2011, and September, 2016.
-positive patients were subsequently stratified according to success of
eradication following targeted antibiotic treatment. CLAD-free and graft survival were compared between
-positive and
-negative patients; and between patients with or without successful
eradication. In addition, pulmonary function was assessed during the first year following
isolation in both groups.CLAD-free survival of
-negative patients (n=443) was longer compared with
-positive patients (n=95) (p=0.045). Graft survival of
-negative patients (n=443, 82%) was better compared with
-positive patients (n=95, 18%) (p<0.0001). Similarly,
-eradicated patients demonstrated longer CLAD-free and graft survival compared with patients with persistent
Pulmonary function was higher in successfully
-eradicated patients compared with unsuccessfully eradicated patients (p=0.035).
eradication after LTx improves CLAD-free and graft survival and maintains pulmonary function. Therefore, early
detection and eradication should be pursued.
OBJECTIVE:We undertook a systems immunology approach of the adaptive immune system in multiple sclerosis (MS), overcoming tradeoffs between scale and level of detail, in order to identify the ...immunologic signature of MS and the changes wrought by current immunomodulatory treatments.
METHODS:We developed a comprehensive flow cytometry platform measuring 38 immunologic cell types in the peripheral blood of 245 individuals in a routine clinical setting. These include patients with MS, untreated or receiving any of 4 current immunomodulatory treatments (interferon-β, glatiramer acetate, natalizumab, or fingolimod), patients with autoimmune thyroid disease, and healthy controls.
RESULTS:An increase in memory CD8 T cells and B cells was observed in untreated patients with MS. Interferon-β and fingolimod induce significant changes upon multiple aspects of the peripheral immune system, with an unexpectedly prominent alteration of B cells. Overall, both treatments push the immune system in different directions, with only 2 significant effects shared across these treatments—an increase in transitional B cells and a decrease in class-switched B cells. We further identified heightened B cell-activating factor (BAFF) levels as regulating this shared B cell pathway.
CONCLUSIONS:A systems immunology approach established different immunologic profiles induced by current immunomodulatory MS treatments, offering perspectives for personalized medicine. Pathways shared between the immunologic architecture of existing efficacious treatments identify targets for future treatment design.
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