Alterations of naïve and memory B-cell subsets are associated with risk of rejection and infection in heart recipients

Lanio, N.; Sarmiento, E.; Gallego, A.; Calahorra, Leticia; Jaramillo, María; Navarro, J.; Palomo, Jesús; Fernàndez-Yáñez, J.; Ruíz, Manuel; Fernández‐Cruz, Eduardo; Carbone, Javier

doi:10.1111/tri.12131

Cited by 11 publications

(4 citation statements)

References 34 publications

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“…It is tempting to speculate that a protective effect of rituximab in immunologically high-risk patients could be explained by reducing the relatively high pretransplant levels of memory B cells in our immunologically high-risk patients. Indeed, an increase in circulating memory B cells has been associated with acute rejection in pediatric renal transplant recipients (17), while heart transplant recipients with higher percentages of na€ ıve B cells had a lower risk of acute rejection (18). However, we and others have previously shown that memory B cells are more resistant to depletion by rituximab than na€ ıve B cells (19,20).…”

Section: Discussionmentioning

confidence: 88%

“…Indeed, an increase in circulating memory B cells has been associated with acute rejection in pediatric renal transplant recipients (17), while heart transplant recipients with higher percentages of na€ ıve B cells had a lower risk of acute rejection (18). However, we and others have previously shown that memory B cells are more resistant to depletion by rituximab than na€ ıve B cells (19,20).…”

Section: Rituximab In Renal Transplantationmentioning

confidence: 89%

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Rituximab as Induction Therapy After Renal Transplantation: A Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety

Hoogen

Kamburova

Baas

et al. 2015

American Journal of Transplantation

105

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We evaluated the efficacy and safety of rituximab as induction therapy in renal transplant patients. In a double‐blind, placebo‐controlled study, 280 adult renal transplant patients were randomized between a single dose of rituximab (375 mg/m2) or placebo during transplant surgery. Patients were stratified according to panel‐reactive antibody (PRA) value and rank number of transplantation. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil and steroids. The primary endpoint was the incidence of biopsy proven acute rejection (BPAR) within 6 months after transplantation. The incidence of BPAR was comparable between rituximab‐treated (23/138, 16.7%) and placebo‐treated patients (30/142, 21.2%, p = 0.25). Immunologically high‐risk patients (PRA >6% or re‐transplant) not receiving rituximab had a significantly higher incidence of rejection (13/34, 38.2%) compared to other treatment groups (rituximab‐treated immunologically high‐risk patients, and rituximab‐ or placebo‐treated immunologically low‐risk (PRA ≤ 6% or first transplant) patients (17.9%, 16.4% and 15.7%, p = 0.004). Neutropenia (<1.5 × 109/L) occurred more frequently in rituximab‐treated patients (24.3% vs. 2.2%, p < 0.001). After 24 months, the cumulative incidence of infections and malignancies was comparable. A single dose of rituximab as induction therapy did not reduce the overall incidence of BPAR, but might be beneficial in immunologically high‐risk patients. Treatment with rituximab was safe.

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Section: Discussionmentioning

confidence: 88%

Section: Rituximab In Renal Transplantationmentioning

confidence: 89%

Rituximab as Induction Therapy After Renal Transplantation: A Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety

Hoogen

Kamburova

Baas

et al. 2015

American Journal of Transplantation

105

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“…In animal models, the reduction in naïve B cells promotes Cryptococcus dissemination (35) and the lower biodiversity of BCR sequences with SHM in patients with SLE (34) may diminish the B cell repertoire to combat infections. Also, the lower pool of naïve B cells could lead to less class-switched memory B cells, which are known to be fundamental in the prevention of infections in other clinical conditions (36). The combination of a lower naïve B cell repertoire and diminished SHM may explain the increased risk of infection in SLE patients, although further studies are required to assess if different B cell subsets are involved in infection development in these patients.…”

Section: Discussionmentioning

confidence: 99%

The Systemic Lupus Erythematosus Infection Predictive Index (LIPI): A Clinical-Immunological Tool to Predict Infections in Lupus Patients

et al. 2019

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Among autoimmune diseases, systemic lupus erythematosus (SLE) patients have a unique predisposition to develop infections, which represents one of their main causes of morbidity and mortality. Many infections occur at disease diagnosis in the absence of immunosuppressive therapy, suggesting that the immunological abnormalities in SLE patients might be fundamental for the development of this complication. The aim of this study was to address the main clinical and immunological features associated with the development of infection and to create and validate a compound clinical-immunological infection predictive index in a cohort of SLE patients. We included 55 SLE patients with < 5 years since diagnosis. The clinical and immunological features were evaluated periodically and patients were followed-up during 1 year, searching for the development of infection. Immunophenotyping was performed by multiparametric flow cytometry and neutrophil extracellular traps (NETs) were assessed by confocal microscopy. Eighteen patients (32.7%) presented 19 infectious events, 5 (26.3%) were severe. For the construction of the index, we performed a logistic regression analysis and the cutoff points were determined with ROC curves. Increased numbers of peripheral Th17 cells, B cell lymphopenia, and lower TLR2 expression in monocytes, as well as the use of cyclophosphamide were the major risk factors for the development of infection and thus were included in the index. Besides, patients that developed infection were characterized by increased numbers of low-density granulocytes (LDGs) and higher expression of LL-37 in NETs upon infection. Finally, we validated the index retrospectively in a nested case-control study. A score >1.5 points was able to predict infection in the following year (AUC = 0.97; LR– = 0.001, specificity 100%, P = 0.0003). Our index encompasses novel immunological features able to prospectively predict the risk of infection in SLE patients.

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“…Moreover, increased expression of CD31 on plasma cells correlates with the mRNA expression profile in plasmablasts and plasma cells [ 35 ]. The investigation of CD31 and CD39 expression can be a useful tool for plasma cell characterization and may allow uncovering subsets with specific roles during an immune response as recently reported [ 60 , 61 ]. Furthermore, the coexpression of CD31 and its ligand CD38, on plasma cells [ 62 ] suggests a role for this interaction in the plasma cell survival niche as already proposed for leukemia cells [ 52 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Human CD38^hiCD138⁺Plasma Cells Can Be Generated In Vitro from CD40-Activated Switched-Memory B Lymphocytes

Maïga

Bonnaure

Rochette

et al. 2014

Journal of Immunology Research

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B lymphocyte differentiation into long-lived plasma cells is the keystone event for the production of long-term protective antibodies. CD40-CD154 and CD27-CD70 interactions are involved in human B lymphocyte differentiation into CD38hiCD138+ cells in vivo as well as in vitro. In this study, we have compared these interactions in their capacity to drive switched-memory B lymphocytes differentiation into CD38hiCD138+ plasma cells. The targeted B lymphocytes were isolated from human peripheral blood, expanded for 19 days, and then submitted to CD70 or CD154 interactions for 14 days. The expanded B lymphocytes were constitutively expressing CD39, whereas CD31's expression was noticed only following the in vitro differentiation step (day 5) and was exclusively present on the CD38hi cell population. Furthermore, the generated CD38hiCD138+ cells showed a higher proportion of CD31+ cells than the CD38hiCD138− cells. Besides, analyses done with human blood and bone marrow plasma cells showed that in vivo and de novo generated CD38hiCD138+ cells have a similar CD31 expression profile but are distinct according to their reduced CD39 expression level. Overall, we have evidences that in vitro generated plasma cells are heterogeneous and appear as CD39+ precursors to the ones present in bone marrow niches.

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Alterations of naïve and memory B-cell subsets are associated with risk of rejection and infection in heart recipients

Cited by 11 publications

References 34 publications

Rituximab as Induction Therapy After Renal Transplantation: A Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety

Rituximab as Induction Therapy After Renal Transplantation: A Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety

The Systemic Lupus Erythematosus Infection Predictive Index (LIPI): A Clinical-Immunological Tool to Predict Infections in Lupus Patients

Human CD38^hiCD138⁺Plasma Cells Can Be Generated In Vitro from CD40-Activated Switched-Memory B Lymphocytes

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Alterations of naïve and memory B-cell subsets are associated with risk of rejection and infection in heart recipients

Cited by 11 publications

References 34 publications

Rituximab as Induction Therapy After Renal Transplantation: A Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety

Rituximab as Induction Therapy After Renal Transplantation: A Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety

The Systemic Lupus Erythematosus Infection Predictive Index (LIPI): A Clinical-Immunological Tool to Predict Infections in Lupus Patients

Human CD38hiCD138+Plasma Cells Can Be Generated In Vitro from CD40-Activated Switched-Memory B Lymphocytes

Contact Info

Product

Resources

About

Human CD38^hiCD138⁺Plasma Cells Can Be Generated In Vitro from CD40-Activated Switched-Memory B Lymphocytes