Changes in T and B cell subsets in end stage renal disease patients before and after kidney transplantation

Abstract Background The incidence of kidney transplantation performed in elderly patients has increased steadily recently. Higher risk of infection and mortality, but lower rate of rejection, are reported in older kidney transplant patients. This study aims to analyze the effect of transplantation on aging of T and B cells in kidney transplant patients, with the emphasis on age and Cytomegalovirus (CMV) latency. Results We included 36 patients before and after (median 2.7 years) kidney transplantation and 27 age- and sex-matched healthy controls (HC). T and B cell subsets were measured by flow cytometry, with a focus on aged T cells (CD28-), and age associated B cells (ABCs, CD19 + CD21-CD11c+). Three years after transplantation a significant increase of total T cells among the lymphocytes was found compared to pre-transplantation and HC. Among the T cells CD4+ cells were decreased, especially naïve CD4+ cells and regulatory T cells. Total CD8+ cell proportions were increased, and proportions of naïve CD8+ cells were significantly decreased after transplantation, while CD8+ effector memory T cells re-expressing CD45RA were increased. CD28− T cells were significantly higher compared to HC after transplantation, especially in CMV seropositive patients. B cells were significantly decreased, while among B cells memory B cells and especially ABCs were increased after transplantation. Conclusions After transplantation T and B cell subsets change towards more terminally differentiated memory cells compared to age-matched HC. Proportions of aged T cells and ABCs were associated with CMV serostatus.

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POS0003 RITUXIMAB THERAPY IN SYSTEMIC LUPUS ERYTHEMATOSUS – TRANSIENT EFFECTS ON AGE ASSOCIATED B-CELLS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2366 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 203.1-204

Author(s):

F. Faustini ◽

N. Sippl ◽

R. Stålesen ◽

K. Chemin ◽

I. Gunnarsson ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

B Cell ◽

T Cell Subsets ◽

Cd4 Cells ◽

Helper Cells ◽

B Cell Subsets ◽

Anti Cd20

Background:Immune system’s abnormalities in SLE involve several subsets of the B-cell compartment, including double negative B-cells (DN) and CD11c+CD21- B cells (also referred to as ABC-age associated B cells), which are expanded in the disease. ABC cells are also known to interact with T helper cells, T follicular and peripheral helper cells (1). Rituximab, a chimeric anti- CD20 antibody, depleting B cells, is commonly used off-label as treatment for SLE patients, especially in lupus nephritis. Little is known on the impact of B-cell depletion on such B-cell subsets and on B-T-cell interactions.Objectives:to investigate the effects of rituximab (RTX) on the frequencies of double negative B-cell subsets and CD11c+CD21- ABC cells and as well as T follicular helper (TFH, CXCR5+ PD-1+) and T peripheral helper (TPH, PD-1high) CD4+ T-cell subsets.Methods:15 SLE patients, starting RTX and followed longitudinally up to two years, were analyzed for lymphocyte subsets using multicolor flow cytometry. Cryopreserved PBMC were thawed and stained at the same time together with one buffy coat. Around 1 x 106 PBMC for each panel were labeled and further stained with fluorescent antibodies for B and T-cell markers. For the B-cell panel, PBMC were stained with anti-CD3, CD14, CD16, CD19, IgD, CD27, CD38, CD11c, CD21 and in some samples with anti-CXCR5 antibodies. For the T-cell panel, PBMC were labeled with anti-CD16, CD14, CD19 and CD3, CD4, CD8, PD-1, CCR7, CXCR5, CD45RA antibodies. All patients fulfilled the ACR 1982 classification criteria for SLE. Cellular changes were analyzed in the context of clinical information.Results:in the present cohort, the SLE patients were mainly female (86.6%) and of median age of 36.7 (29.8-49.4) with a disease duration of 6.1(1.6-11.8) years, and active disease with SLEDAI-2K at baseline 12.0 (8.0-16.0). The frequency of age-associated B cells (ABCs; CD27-IgD-CD11c+ CD21-) decreased by 13% (p=0.03) in the first two to four months after rituximab start, while globally the DN (IgD-CD27-) B cells transiently increased by around 3% (p=0.15) at the first follow-up. This increase could not be attributed to the DN1 (CXCR5+CD11c-) or DN2 (CXCR5-CD11c+) subsets but to the CD11c-CXCR5- DN (DN3) B cells (increase= 6.7%, p=0.03). In parallel, T effector cells (CCR7- CD45RA+) and TEMRA (CD45RA+ CCR7-) frequencies increased after first follow up in both CD4+ and CD8+ T cells. The frequency of TFH (CXCR5+ PD-1+) cells did not change after rituximab, however a decrease of PD-1high CD4+ cells was observed in most patients, although not significant, after 2-4 month of treatment. In most patients the frequency of PD-1high CD4+ cells either reduce or stay the same after RTX treatment (reduction= 0.53, p=0.28). After 11-15 months of RTX treatment the frequency of PD-1high CD4+ T cell reduces by a -0.5% in comparison to 2-4 months (p=0.039). The SLEDAI at baseline did not correlate with the frequency of PD-1high CD4+ T cells (r=0.03, p=0.9).Conclusion:the importance of T cell - B cell interactions in SLE pathogenesis was recently strengthened by the identification of the lymphocyte subsets TFH/TPH and ABCs respectively. Here, in the context of rituximab treated SLE, we could detect a reduction in the frequencies of both ABCs and PD-1high T cells after treatment with rituximab, while the DN3 and effector memory T cells frequencies increased. Our data suggests that anti-CD20 mediated B-cell depletion affects both B-cell and T-cell subsets frequencies, and that monitoring these specific cell subsets may be clinically relevant.References:[1]Bocharnikov AV, Keegan J, Wacleche VS, Cao Y, Fonseka CY, Wang G, et al. PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. JCI insight. 2019;4(20)Disclosure of Interests:Francesca Faustini Speakers bureau: More than two years ago and not in relation to any aspect of the present research, Natalie Sippl: None declared, Ragnhild Stålesen: None declared, Karine Chemin: None declared, Iva Gunnarsson: None declared, Vivianne Malmström: None declared.

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FTY720 treatment of kidney transplant patients: A differential effect on B cells, naïve T cells, memory T cells and NK cells

Transplant Immunology ◽

10.1016/j.trim.2006.02.002 ◽

2006 ◽

Vol 15 (4) ◽

pp. 281-288 ◽

Cited By ~ 35

Author(s):

Leonard M.B. Vaessen ◽

Nicole M. van Besouw ◽

Wendy M. Mol ◽

Jan N.M. IJzermans ◽

Willem Weimar

Keyword(s):

T Cells ◽

B Cells ◽

Nk Cells ◽

Kidney Transplant ◽

Differential Effect ◽

Memory T Cells ◽

Naive T Cells ◽

Naïve T Cells ◽

Transplant Patients ◽

Kidney Transplant Patients

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ANALYSIS OF ALLOSPECIFIC T CELLS IN KIDNEY TRANSPLANT PATIENTS ON VARIOUS IMMUNOSUPPRESSIVE PROTOCOLS.

Transplantation Journal ◽

10.1097/00007890-200607152-01876 ◽

2006 ◽

Vol 82 (Suppl 2) ◽

pp. 692

Author(s):

&NA;

Keyword(s):

T Cells ◽

Kidney Transplant ◽

Transplant Patients ◽

Kidney Transplant Patients

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SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00749-3 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Yukai Jing ◽

Li Luo ◽

Ying Chen ◽

Lisa S. Westerberg ◽

Peng Zhou ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Immune Regulation ◽

Cell Metabolism ◽

Healthy Controls ◽

Bcr Signaling ◽

Before And After ◽

B Cell Subsets ◽

Almost All ◽

Cd19 Expression

AbstractThe SARS-CoV-2 infection causes severe immune disruption. However, it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients. In our study, we have characterized the immune phenotype of B cells from 15 recovered COVID-19 patients, and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation, but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation. However, the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation. Interestingly, we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients. Moreover, the BCR signaling and early B-cell response were disrupted upon BCR stimulation. Mechanistically, we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism. In conclusion, we found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism, which may provide a new intervention target to cure COVID-19.

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Evaluation of Quality of Life among Kidney Transplant Patients- A Cross Sectional Study

10.53350/pjmhs2115113087 ◽

2021 ◽

Vol 15 (11) ◽

pp. 3087-3089

Author(s):

Rashida Jabeen ◽

Kousar Perveen ◽

Muhammad Afzal ◽

Sadia Khan

Keyword(s):

Quality Of Life ◽

Kidney Transplantation ◽

Kidney Transplant ◽

Cross Sectional Study ◽

P Value ◽

Sectional Study ◽

Cross Sectional ◽

Transplant Patients ◽

Kidney Transplant Patients

Kidney transplantation is the famous and most important choice of treatment of renal replacement therapies (RRTs) because of its positive impact on morbidity, survival and cost. The health related quality of life is becoming important outcome. Quality of life is usually impaired in patients who have renal transplant because of renal transplant patients have anxiety, lack of social, physical and emotional support and diminished ability to take care of themselves. The basic purpose of renal transplantation is to achieve maximum quality of life with minimum side effects. Methods: A cross sectional study was conducted at Rukhsana Akhtar Bahria International Orchard Hospital Lahore after approval from institution board of university of Lahore. 36 patients were enrolled in study by using purposive sampling technique. After taking informed consent all Kidney transplant patients aged between 18 years to 60 years, visited the post-transplantation OPD and continuously in follow-up sessions were included in study. A validated and standard WHO questionnaire of “Kidney Disease and Quality of Life (KDQOL-36™)” was used for data collection. Data was entered and analyzed in SPSS version.21.Chi-square test was applied to find out significant association between qualitative variables. P -Value < 0.05will be considered as statistically significant. Results: Majority of patients were from 40-49 years 10(27.0%). Females were more as compared to men (20(55.6) vs 16(44.4%)). 10(27.8) patients can read and write and 8(22.2%) have done matriculation. More patients live in Urban area as compared to rural area(19(52.8%) vs 17(47.2%)).8(22.2%) patients have less than 1 year of post kidney transplantation time and 19(52.8%) have 1 to 3 years. All the seven domains of KDQOL show poor QOL. General Health, Physical function and physical and emotional function shows average QOL and Emotional, social, daily activities and overall KDQOL shows poor QOL. There was insignificant association with age, gender, education; residential area and Post kidney transplantation length of time (years)(p-value > 0.05). Conclusions: After renal transplantation HRQOL becomes very important factor. After kidney transplantation HRQOL depends on many factors. It was concluded from current study that the HRQOL was not as good as it should be. Over the period of transplantation time patient’s quality of life remain same. The society, government, family, and medical staff need to support patients so they can also improve their QOL. Key word: Renal Diseases, Kidney transplant, Quality of life, KDQOL-36

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In VitroMeasles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells

Journal of Virology ◽

10.1128/jvi.00131-18 ◽

2018 ◽

Vol 92 (8) ◽

pp. e00131-18 ◽

Cited By ~ 19

Author(s):

Brigitta M. Laksono ◽

Christina Grosserichter-Wagener ◽

Rory D. de Vries ◽

Simone A. G. Langeveld ◽

Maarten D. Brem ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

B Cell ◽

Immune Suppression ◽

Peripheral Blood ◽

Measles Virus ◽

Memory B Cells ◽

T And B Cells ◽

B Cell Subsets

ABSTRACTMeasles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils toin vitroMV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (TH) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that TH1TH17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression.IMPORTANCEMeasles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the importance of MV infection of B cellsin vivo. However, information on the relative susceptibility of B-cell subsets is scarce. Here, we compared the susceptibility and permissiveness toin vitroMV infection of human naive and memory T- and B-cell subsets isolated from peripheral blood or tonsils. Our results demonstrate that both naive and memory B cells are more permissive to MV infection than T cells. The highest infection levels were detected in plasma cells and germinal center B cells, suggesting that infection and depletion of these populations contribute to reduced host resistance.

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CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients

Journal of Clinical Medicine ◽

10.3390/jcm8081147 ◽

2019 ◽

Vol 8 (8) ◽

pp. 1147 ◽

Cited By ~ 3

Author(s):

Lemerle ◽

Garnier ◽

Planchais ◽

Brilland ◽

Subra ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Kidney Transplant ◽

Cd8 T Cells ◽

De Novo ◽

Predictive Biomarkers ◽

Transplant Patients ◽

History Of ◽

Kidney Transplant Patients ◽

A Prospective Study

Predictive biomarkers of acute rejection (AR) are lacking. Pre-transplant expression of CD45RC on blood CD8+ T cells has been shown to predict AR in kidney transplant (KT) patients. The objective of the present study was to study CD45RC expression in a large cohort of KT recipients exposed to modern immunosuppressive regimens. CD45RC expression on T cells was analyzed in 128 KT patients, where 31 patients developed AR, of which 24 were found to be T-cell mediated (TCMR). Pre-transplant CD4+ and CD8+ CR45RChigh T cell proportions were significantly higher in patients with AR. The frequency of CD45RChigh T cells was significantly associated with age at transplantation but was not significantly different according to gender, history of transplantation, pre-transplant immunization, and de novo donor specific anti-Human Leucocyte Antigen (HLA) antibody. Survival-free AR was significantly better in patients with CD8+ CD45RChigh T cells below 58.4% (p = 0.0005), but not different according to CD4+ T cells (p = 0.073). According to multivariate analysis, CD8+ CD45RChigh T cells above 58.4% increased the risk of AR 4-fold (HR 3.96, p = 0.003). Thus, pre-transplant CD45RC expression on CD8+ T cells predicted AR, mainly TCMR, in KT patients under modern immunosuppressive therapies. We suggest that CD45RC expression should be evaluated in a prospective study to validate its usefulness to quantify the pre-transplant risk of AR.

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