Long Term Humoral Immune Reconstitution Kinetics After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) In Children

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4627-4627
Author(s):  
Amro Elshoury ◽  
Neena Kapoor ◽  
Ami J Shah ◽  
Bhakti Mehta ◽  
Kris M. Mahadeo ◽  
...  
Keyword(s):  
B Cells ◽  
Serum Level ◽  
B Cell ◽  
Immune Reconstitution ◽  
Serum Levels ◽  
Multivariate Regression Analysis ◽  
Memory B Cells ◽  
Post Transplantation ◽  
Humoral Immune ◽  
Cell Counts

Background HSCT recipients have increased incidence of acquiring infections, particularly by encapsulated bacteria such as Streptococcal pneumoniae and Haemophilus influenzae. Delayed immune reconstitution has a pivotal role in these complications. Although T-cell immune reconstitution has been well studied, long-term B-cell reconstitution remains less characterized. Patients and Methods We studied 73 patients, who received allogeneic HSCT at Childrens Hospital Los Angeles. Patients were in complete remission of their underlying disorder and with median follow up 4.15 years [yrs] (range 6 month -18yrs, mean 5 yrs) post-HSCT. All subjects were< 18 years of age. B (naive [IgD+CD27-CD19+], memory [IgD+CD27+CD19+] and switched memory [IgD-CD27+CD19]); and T (CD3+, CD3+CD4+, CD3+CD8+, CD4+CD25+CD127dim (T Regulatory) [Tregs], RA+CD4+) cell subtypes, quantitative Immunoglobulins levels and antibodies to both polyribosyle polyphospate (PRP) and tetanus toxoid (TT) antigens were assessed longitudinally after HSCT. Results Naive B Cells were the first B cell subtype to return to normal value at 6 month post-HSCT, while memory B cells were persistently low up to two years post-HSCT. PRP levels continued to be low up to 10 years post -HSCT in unrelated donor HSCT recipients. TT antibodies level was normal at 6 month post-HSCT following immunization with TT in patients not receiving IVIG therapy. Switched memory B cell counts correlated positively with RA+CD4+ counts at 6 month post-HSCT (r=0.459, P=0.021) and with CD3+CD+4 counts at 6 months (r=0.530, P=0.006) and 2-years post-HSCT (r=0.398, P=0.016). However, switched memory B cells did not correlate with Tregs at any time post-HSCT. Switched memory B cells correlated positively with serum level of IgG at 1 (r=0.443, P=0.039), and 2 years post transplantation (r=0.617, P=0.001) and with serum level of IgA at 2 years post-HSCT(r=0.567. P=0.004). Memory B-cells counts correlated positively with serum levels of IgM at 1 year post-HSCT (r=0.478, P=0.021) and with serum levels of both IgG and IgA (r=0.431 P=0.035, and r=0.416, P=0.043, respectively) at 2 years post-HSCT. However, memory B-cell counts did not correlate with RA+CD4+, CD3+CD4+, CD3+CD8+ or Tregs cell counts. The use of Total body irradiation (TBI) was associated with lower switched memory B cells at 2 years (P=0.01) post-HSCT. TBI recipients also have lower PRP levels at 6-month post-HSCT compared to patients who did not receive TBI. Age of the recipient at time transplantation is another independent factor affecting all the B cell subsets recovery after transplantation; increase in age at transplantation is associated with lower B cell recovery. Decreased memory B cells post-HSCT was observed in patients with history of acute graft versus host disease (GVHD) (P=0.034) and chronic GVHD (P=0.01), even after resolution of clinical manifestations of active GVHD at 6 month and 2 years follow up, respectively. Compared to cord blood graft recipients, Bone marrow graft recipients have increased switched memory B-cells at 6 month and higher (P=0.0001) PRP antibodies titer at 3 years post-HSCT, respectively. Patients who did not receive ATG or Alemtuzumab have increased recovery of naive B-cells (P=0.024) at 2 years post-transplantation. Patients received ATG have higher both naive B cells in univariate analysis and PRP levels (in multivariate analysis) than those received Alemtuzumab at 6 months post-HSCT. Multivariate regression analysis showed that patients received Alemtuzumab have higher TT antibodies titer at 6 month post -HSCT compared to those received ATG. Conclusion We have found that memory and switched memory B-cells and serum PRP levels are deficient post-HSCT in children. Switched memory B cells correlated positively with serum level of IgG and IgA and memory B-cells correlated positively with serum levels of IgM, IgG and IgA. This confirms that HSCT recipients have impaired humoral immune reconstitution, hindering both B-cells development and generation of immunoglobulins. We also studied the different factors affecting humoral immune reconstitution using backwards multivariate regression analysis model and found that the use of TBI, age of the recipient at transplantation, GVHD status and source of stem cells can affect the kinetics of humoral immune reconstitution after HSCT in children. Disclosures: No relevant conflicts of interest to declare.

scholarly journals B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy

Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5571-5579 ◽  
Author(s):  
Susan Moir ◽  
Clarisa M. Buckner ◽  
Jason Ho ◽  
Wei Wang ◽  
Jenny Chen ◽  
...  
Keyword(s):  
B Cells ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
B Cell ◽  
Immune Cell ◽  
Memory B Cells ◽  
Early Initiation ◽  
Cell Counts ◽  
The Impact ◽  
Chronic Hiv Infection

Abstract Characterization of lymphocytes including B cells during early versus chronic HIV infection is important for understanding the impact of chronic viremia on immune cell function. In this setting, we investigated B cells before and after reduction of HIV plasma viremia by antiretroviral therapy (ART). At baseline, peripheral blood B-cell counts were significantly lower in both early and chronic HIV-infected individuals compared with uninfected controls. Similar to CD4+ but not CD8+ T cells, B-cell numbers in both groups increased significantly after ART. At baseline, B cells of early HIV-infected individuals were composed of a higher percentage of plasmablasts and resting memory B cells compared with chronic HIV-infected individuals whose B cells were composed of a higher percentage of immature/transitional and exhausted B cells compared with their early infection counterparts. At 1 year after ART, the percentage of resting memory B cells remained higher in early compared with chronic HIV-infected individuals. This difference translated into a better functional profile in that memory B-cell responses to HIV and non-HIV antigens were superior in early- compared with chronic-treated HIV infected individuals. These findings provide new insights on B cells in HIV infection and how early initiation of ART may prevent irreversible immune system damage.

Rituximab during Pregnancy: Serum Levels, B Cell Counts and Immunoglobulin Levels in Mother and Child.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1508-1508
Author(s):  
Birte Friedrichs ◽  
Markus Tiemann ◽  
Michael K. Wenger ◽  
Karl Verpoort ◽  
Norbert Schmitz
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Serum Levels ◽  
Burkitt’S Lymphoma ◽  
Cell Counts ◽  
Mother And Child ◽  
Newborn Child ◽  
Immunoglobulin Levels

Abstract Recently the first cases of lymphoma patients treated with rituximab and combination chemotherapy during pregnancy were reported. We report on a patient with Burkitt’s lymphoma who was treated with rituximab and CHOP therapy early during pregnancy. We were able to monitor rituximab concentrations, B-/T- cell counts and immunoglobulin levels. After delivery these parameters were also measured in the newborn child. A 35-year-old female was diagnosed with CD20+ Burkitt’s lymphoma of the left breast in week 15 of pregnancy. The minimum stage was IIEA; however, the patient also had hepatosplenomegaly. We started treatment with four weekly infusions of rituximab (375mg/m2)(week 16,17,18,19). Treatment was well tolerated with minimal side effects; a minor response was documented by MRI of the breast and ultrasound of previously enlarged axillary lymph nodes. At that time, a decision was made to continue treatment with 6 courses of Cyclophosphamid, Doxorubicin, Vincristin and Prednison (CHOP) at 3 week intervals (week 21, 24, 27, 30, 33, 36). The first 4 courses were preceded by rituximab (375mg/m2). Immunotherapy was tolerated without significant problems. At the end of therapy (week 37) a complete remission was achieved, again documented by MRI and ultrasound. During therapy the child’s growth and intrauterine development were closely monitored by the attending gynecologist. No deviation from normal development were registered. In week 41 of pregnancy the patient delivered a healthy girl (3780g, 55cm, APGAR score 9/10/10) via caesarean section. The girl is now 19 month old, has repeatedly been seen by her pediatrician who reported completely normal growth and developmental status. The mother received high-dose therapy (BEAM) followed by autologous peripheral blood stem cell transplantion 2 months after delivery and has remained in CR with a normal performance status. As the mother has been extremely compliant we were able to repeatedly measure B cell counts, immunoglobulin levels and rituximab concentrations not only in the patient but also in the baby (table 1). Interestingly, at the time of birth very high serum levels of rituximab were measured in the child. Nonetheless a normal B cell recovery was seen during the following weeks, immunological status reached normal values 4 month after delivery and no overt infectious complications have been reported. As to our knowledge, for the first time data of rituximab serum concentrations are available from mother and child. To conclude, in this case combination of immuno- and chemotherapy could be safely administered, achieving a CR in the patient without causing any mental or developmental retardation in the newborn child. In accordance with other reports, this case supports the safety and efficacy of Rituximab administration during pregnancy. Table 1: B/T cell counts and Rituximab concentrations in mother and child during and after treatment with R-CHOP Time Mother Child *values within normal range week of pregnancy/ B-cells T-cells Rituximab B-cells T-cells Rituximab week after delivery CD 19+ CD 3+ CD 19+ CD 3+ cells/μl cells/μl ng/mL cells/μl cells/μl ng/mL 20 0 946 27 0 640 34 4 337 at birth 0 779 9750 0 93 32095 +4 0 759 70 6616* 5399 +18 37 504 &lt;500 1460* 5475* 700

Reduced Circulating Memory B-Cells Account for Humoral Immune Defects in Multiple Myeloma, Associated with Infective Risk and Poor Vaccination Responses

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3393-3393
Author(s):  
Jonathan Carmichael ◽  
Clive R Carter ◽  
Christopher Parrish ◽  
Charlotte Kallmeyer ◽  
Sylvia Feyler ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Bacterial Infections ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Progressive Reduction ◽  
Cell Numbers ◽  
Humoral Immune ◽  
Transitional B Cells ◽  
B Cell Subsets

Abstract Multiple myeloma (MM) is characterized by an increased risk of infection due to the immunosuppressive effect of the disease and conjointly of therapy. Furthermore, there is impaired responses to vaccination to counter the infection risk. The factors that underpin defective B-cell homeostasis and effective humoral immunity are not clear, nor are the extent of the defects. Also, the level of impaired humoral immunity in MGUS is not fully understood. The aim of this study was to delineate the circulating B-cell populations and recall antibody responses in patients with MGUS & MM, compared to age-matched controls, correlating with the responsiveness to vaccinations, incidence of infective complications and concomitant therapy. We performed comprehensive B-cell immunophenotyping by multi-parameter flow cytometry of peripheral blood samples from patients with MGUS (n=16), asymptomatic MM (n=18) and MM (n=108) with a median age of 63 years (range 38-94) comparing them to age-matched controls (n=9). B-cell subsets included naïve (CD19+CD27-), memory (CD19+CD27+; non-switch CD19+IgD+CD27+, switch CD19+IgD-CD27+), transitional (CD19+CD27-CD24hiCD38hi) & regulatory (CD19+CD27+CD24hi) B-cells. Serum uninvolved total IgG, IgM & IgA levels along with vaccine-specific antibody responses were analysed. There is a progressive decrease in the uninvolved immunoglobulin classes with significant reduction in total IgA (p=0.006) and IgM levels (p=0.007) in aMM/MM compared to MGUS & control (Figure 1). When anti-pneumococcal antibodies were measured, only 30% of aMM/MM patients had adequate protective levels compared to 79% of age-matched controls, with 40% of aMM/MM patients with inadequate levels experiencing recurrent respiratory tract infections compared to 25% of aMM/MM patients with adequate proactive antibodies. Patients with MGUS, aMM and MM have lower total B-cell numbers compared to controls (1-way ANOVA p=0.004; Figure 1). The reduction in B-cell numbers were primarily the consequence of reduced memory B-cells (percentage and absolute 1-way ANOVA p<0.0001), noted in both MGUS and aMM/MM but a progressive reduction with increasing disease activity (MGUS>aMM>MM). Furthermore, a correlation with total IgG levels & memory B-cell numbers is evident (r2=-0.053) & progressive reduction in memory B-cell numbers is seen with advancing cycles of therapy. The ratio of switch:non-switch memory B-cells is unaltered (control 1.05, MGUS 0.53, aMM 1.41 & MM 1.49; 1-way ANOVA p=ns). Conversely, there is a compensatory increase in the percentage of transitional B-cells when increasing disease stage is compared to controls (control 7.38% (95%ci 4.9,9.9) vs MGUS 14.0% (95%ci 7.4, 20.7) vs aMM 14.95% (95%ci 8, 21.9); 1-way ANOVA p<0.001) but a reduction is noted in MM (5.82%, 95%ci 4.5,7.2; p<0.0001), primarily being driven by sequential lines of therapy. As a consequence, the ratio of Memory:transitional B-cells is significantly reduced in aMM/MM compared to MGUS & controls (control 10.35, MGUS 20.46, aMM 7.74 & MM 4.57; 1-way ANOVA p=0.006), associated with increasing incidence of bacterial infections. A non-significant correlation is seen between transitional B-cells and total uninvolved immunoglobulin levels and with recall responses to vaccinations. There is a progressive decrease in the CD19+CD27+CD24hi B-cell subset between control and plasma cell dyscrasias (control 20.4% (95%ci 15.5,25.2), MGUS 14.0% (95%ci 7.4, 20.7), aMM 14.95% (95%ci 8, 21.9) & MM 5.82%, 95%ci 4.5,7.2; p<0.0001), primarily being driven by sequential lines of therapy and associated with increased incidence of infection. This study illustrates that patients with myeloma demonstrate reduced total circulating B-cells primarily as a consequence of reduced memory B-cells, associated with reduced immunoglobulin and recall antibody responses. This is associated with increased incidence of bacterial infections and is worsened by sequential exposure to lymphodepleting therapies. Of particular importance is the identified aberration in B-cell subsets seen in MGUS compared with age-matched control, indicative of humoral immune dysregulation highlighting that MGUS may not be an immunologically inert disorder. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

IgM+ memory B cells induced in response to Plasmodium berghei adopt a germinal centre B cell phenotype during secondary infection

Parasitology ◽  
2020 ◽  
Vol 147 (9) ◽  
pp. 994-998 ◽  
Author(s):  
Halina M. Pietrzak ◽  
Lisa J. Ioannidis ◽  
Diana S. Hansen
Keyword(s):  
B Cells ◽  
B Cell ◽  
Plasma Cells ◽  
Secondary Infection ◽  
Memory B Cells ◽  
Germinal Centre ◽  
Cell Phenotype ◽  
Memory B Cell ◽  
Humoral Immune ◽  
Transfer Strategies

AbstractEmerging evidence started to delineate multiple layers of memory B cells, with distinct effector functions during recall responses. Whereas most studies examining long-lived memory B cell responses have focussed on the IgG+ memory B cell compartment, IgM+ memory B cells have only recently started to receive attention. It has been proposed that unlike IgG+ memory B cells, which differentiate into antibody-secreting plasma cells upon antigen re-encounter, IgM+ memory B cells might have the additional capacity to establish secondary germinal centre (GC) responses. The precise function of IgM+ memory B cells in the humoral immune response to malaria has not been fully defined. Using a murine model of severe malaria infection and adoptive transfer strategies we found that IgM+ memory B cells induced in responses to P. berghei ANKA readily proliferate upon re-infection and adopt a GC B cell-like phenotype. The results suggest that that IgM+ memory B cells might play an important role in populating secondary GCs after re-infection with Plasmodium, thereby initiating the induction of B cell clones with enhanced affinity for antigen, at faster rates than naive B cells.

scholarly journals Increased Production of B-Cell Activating Cytokines and Altered Peripheral B-Cell Subset Distribution during HIV-Related Classical Hodgkin Lymphoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 128
Author(s):  
Raphael Lievin ◽  
Houria Hendel-Chavez ◽  
Aliou Baldé ◽  
Rémi Lancar ◽  
Michèle Algarte-Génin ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Activation ◽  
Cell Subset ◽  
Serum Levels ◽  
Classical Hodgkin Lymphoma ◽  
Cell Counts ◽  
Cytokine Levels ◽  
B Cell Subsets

Classical Hodgkin Lymphoma incidence increases in HIV-1-infected patients (HIV-cHL). HIV infection is associated with higher B-cell activation. Here, in 38 HIV-cHL patients from the French cohort ANRS-CO16 Lymphovir, we examined longitudinally over 24 months the serum levels of the B-cell activating cytokines IL10, IL6, and BAFF, and blood distribution of B-cell subsets. Fourteen HIV-cHL patients were also compared to matched HIV-infected controls without cHL. IL10, IL6, and BAFF levels were higher in HIV-cHL patients than in controls (p < 0.0001, p = 0.002, and p < 0.0001, respectively). Cytokine levels increased in patients with advanced-stage lymphoma compared to those with limited-stage (p = 0.002, p = 0.03, and p = 0.01, respectively). Cytokine levels significantly decreased following HIV-cHL diagnosis and treatment. Blood counts of whole B-cells were similar in HIV-cHL patients and controls, but the distribution of B-cell subsets was different with higher ratios of naive B-cells over memory B-cells in HIV-cHL patients. Blood accumulation of naive B-cells was more marked in patients with advanced cHL stages (p = 0.06). During the follow-up, total B-cell counts increased (p < 0.0001), and the proportion of naive B-cells increased further (p = 0.04). Together the results suggest that in HIV-infected patients, cHL is associated with a particular B-cell-related environment that includes increased production of B-cell-activating cytokines and altered peripheral distribution of B-cell subsets. This B-cell-related environment may fuel the process of tumorigenesis.

scholarly journals Targeting human langerin promotes HIV-1 specific humoral immune responses

2021 ◽  
Vol 17 (7) ◽  
pp. e1009749
Author(s):  
Jérôme Kervevan ◽  
Aurélie Bouteau ◽  
Juliane S. Lanza ◽  
Adele Hammoudi ◽  
Sandra Zurawski ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Serum Levels ◽  
Target Antigen ◽  
Humoral Immune ◽  
Cell Functions ◽  
Tfh Cells ◽  
Specific Igg ◽  
Hiv 1

The main avenue for the development of an HIV-1 vaccine remains the induction of protective antibodies. A rationale approach is to target antigen to specific receptors on dendritic cells (DC) via fused monoclonal antibodies (mAb). In mouse and non-human primate models, targeting of skin Langerhans cells (LC) with anti-Langerin mAbs fused with HIV-1 Gag antigen drives antigen-specific humoral responses. The development of these immunization strategies in humans requires a better understanding of early immune events driven by human LC. We therefore produced anti-Langerin mAbs fused with the HIV-1 gp140z Envelope (αLC.Env). First, we show that primary skin human LC and in vitro differentiated LC induce differentiation and expansion of naïve CD4+ T cells into T follicular helper (Tfh) cells. Second, when human LC are pre-treated with αLC.Env, differentiated Tfh cells significantly promote the production of specific IgG by B cells. Strikingly, HIV-Env-specific Ig are secreted by HIV-specific memory B cells. Consistently, we found that receptors and cytokines involved in Tfh differentiation and B cell functions are upregulated by LC during their maturation and after targeting Langerin. Finally, we show that subcutaneous immunization of mice by αLC.Env induces germinal center (GC) reaction in draining lymph nodes with higher numbers of Tfh cells, Env-specific B cells, as well as specific IgG serum levels compared to mice immunized with the non-targeting Env antigen. Altogether, we provide evidence that human LC properly targeted may be licensed to efficiently induce Tfh cell and B cell responses in GC.

Abatacept Reduces Levels of Switched Memory B Cells, Autoantibodies, and Immunoglobulins in Patients with Rheumatoid Arthritis

2014 ◽  
Vol 41 (4) ◽  
pp. 666-672 ◽  
Author(s):  
Mirko Scarsi ◽  
Lucia Paolini ◽  
Doris Ricotta ◽  
Antonio Pedrini ◽  
Silvia Piantoni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Serum Levels ◽  
Memory B Cells ◽  
Cell Phenotype ◽  
B Cell Activation ◽  
Switch Memory

Objective.Abatacept (ABA) is a chimeric molecule, able to block the CD28-mediated costimulatory pathway. To evaluate the hypothesis that, through this mechanism of action, ABA may down-modulate the immune responses of B lymphocytes in rheumatoid arthritis (RA), we investigated the serum levels of immunoglobulins (Ig), free light chains (FLC), anticitrullinated protein antibodies (ACPA), and rheumatoid factor (RF), as well as the number of B lymphocytes differentiated into post-switch memory cells in patients treated with ABA.Methods.The serum levels of Ig, FLC, different ACPA, RF isotypes, and the B cell phenotype were longitudinally evaluated in 30 patients with RA treated with ABA.Results.At baseline, the proportion of total and post-switch memory B cells was lower in RA than in healthy individuals. After 6 months of ABA treatment we observed significant reductions of serum levels of IgG, IgA, and IgM, as well as FLC, with a normalization in many patients who had initially abnormal values. A significant reduction of the titers of IgG- and IgA-ACPA, as well as of IgM-, IgA-, and IgG-RF was also observed. A decrease of autoantibodies below the upper limits of normal values was found in 2 of 26 patients (8%) initially seropositive for IgG-ACPA, 1 of 14 (7%) for IgA-ACPA, 5 of 22 (23%) for IgM-RF, 7 of 22 (30%) for IgA-RF, and 5 of 16 (31%) for IgG-RF. After treatment, the proportion of circulating post-switch memory B cells was also further significantly decreased.Conclusion.ABA treatment in patients with RA can reduce signs of polyclonal B cell activation, inducing a trend toward normalization of serum levels of different classes of Ig and of FLC, decreasing titers of ACPA and RF, and percentages of post-switch memory B cells.

Lymphocyte Subsets In Chronic Gvhd – a Key Role for B Cells?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2311-2311
Author(s):  
Inken Hilgendorf ◽  
Brigitte Mueller-Hilke ◽  
Guenther Kundt ◽  
Ernst Holler ◽  
Petra Hoffmann ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Chronic Gvhd ◽  
Memory B Cells ◽  
Blood Samples ◽  
Cell Counts ◽  
Group 3 ◽  
Group 2 ◽  
B Cell Subsets ◽  
Group 1

Abstract Abstract 2311 Background: Chronic graft-versus host disease (cGVHD) features certain similarities with autoimmune diseases. The pathogenesis of cGVHD after allogeneic hematopoietic stem cell transplantation (alloHSCT), however, is poorly understood. Methods: Peripheral blood samples from 52 pts with active (median day 976, range 177–2773) (group 1), 28 pts with resolved (median day 1207, range 147–2849) (group 2) and 18 pts without cGVHD (median day 1015, range 124–2655) (group 3) were analysed for T and B cell subsets by FACS. 47 pts were transplanted from matched related donors, 40 pts from matched and 11 from mismatched unrelated donors. In addition, blood samples from 20 patients with and 10 patients without history of cGVHD were tested for: antinuclear antibody (ANA), anti-neutrophil cytoplasmatic antibody (ANCA), antimitochondrial antibody (AMA), anti-smooth-muscle antibody (ASMA) and double stranded DNA (dsDNA). Chronic GVHD was evaluated using criteria and guidelines of the National Institute of Health (mild n=16, moderate=18, severe n=18). Results: The absolute CD19+ B cell counts (median in 109/l) in pts with active chronic GVHD (0.03; range 0–2.59) were subnormal and lower than in pts of group 2 (0.140; range 0.001–0.856; p 0.019) and group 3 (0.175; range 0.20–0.553; p 0.002). Significant differences in absolute numbers of the CD27− B cell compartment, including immature (CD19+ CD27− CD38++CD20+IgM+) and transitional B cells (CD19+ CD27− CD38++CD10+CD20+IgM+), (median in 109/l: group1: 0.015; range 0–0.499 vs. group 2: 0.090; range 0–0.667 or vs. group 3: 0.158; range 0.02–0.52; both p<0.001) as well as class switched memory B cells (median in 106/l: 0.045; range 0–96.00 vs. 3.40; range 0–69.35; p 0.032 or vs. 7.40; range 0–56.83; p 0.003) were observed between the groups. Of interest, the CD 27+IgD+IgM+ B cell subpopulation (median in 106/l) is lacking in pts with active cGVHD (0; range 0–1.35) in contrast to patients with resolved (0.43, range 0–17.47; p<0.001) or pts who never experienced cGVHD (1.69; range 0–10.00; p<0.001). The counts of CD8+ T cells (median in 109/l) were significantly lower in pts of group 1 (0.257, range 0.01–1.76) compared to pts of group 2 (0.373; range 0 –1.96; p 0.010) or group 3 (0.545; range 0.06–1.61; p 0.027). No significant differences in CD4+ T cell counts (median in 109/l: 0.274 vs. 0.355 vs. 0.293) including naïve and memory CD4+ T cells as well as regulatory CD25+CD4+ FoxP3+ T cell counts (median in 106/l: 8.11 vs. 6.55 vs. 9.72) were observed between the three groups. In patients with cGVHD ANA was positive in 35% (7/20), ASMA in 20% (4/20) and AMA in 5% (1/20). ANA was positive in 36% (4/11) and ASMA in 27% (3/11) of patients without cGVHD. AMA and dsDNA were negative in all patients without cGVHD and ANCA was negative in all tested patients. 10% (3/31) of patients showed more than one autoantibody. Conclusion: Our data confirm a close association of diminished B cell counts with cGVHD while no difference of the tested autoantibodies was observed between pts with and without cGVHD. The lack of CD 27+IgD+IgM+ B cells in pts with cGVHD indicates functional asplenia in these pts, because IgM+ memory B cells are dependent upon a functional spleen for their generation and/or survival. Analysis of B cell subsets can provide a diagnostic tool for monitoring cGVHD activity but requires prospective evaluation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Altered B cells homeostasis in child-onset immunoglobulin A vasculitis

2020 ◽  
Author(s):  
Deying Liu ◽  
Yanfang Jiang ◽  
Jinghua Wang ◽  
Jinxiang Liu ◽  
Meng Xu ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Mononuclear Cells ◽  
Immunoglobulin A ◽  
Cell Subset ◽  
Memory B Cells ◽  
Peripheral Blood Mononuclear ◽  
Cell Numbers ◽  
Cell Counts ◽  
Immunoglobulin A Vasculitis

AbstractBackgroundImmunoglobulin A vasculitis (IgAV), also called Henoch–Schönlein purpura, is a systemic small vessels vasculitis with immunoglobulin A1-dominant immune deposits. B-cells are a heterogeneous population with unique subsets distinguished by their phenotypes and cytokine production. Here, we explored the status of B cell subsets in patients with IgAV.MethodsThirty IgAV patients and fifteen age- and sex-matched healthy individuals were enrolled in this study. Fresh blood samples were collected from both healthy and IgAV patients. Upon the distinct expressions of CD3, CD19, CD20, CD38, CD27 and IgD, peripheral blood mononuclear cells (PBMCs) were initially categorized into plasmablasts and memory B cells. Subsequently, using surface markers including CD138 and IgM, and intracellular markers containing IgM and IgG, plasmablasts and memory B cells were further divided into distinct subgroups. A total of eleven populations were detected using multiple flow cytometry.ResultsCD3-CD19+IgD+CD27-, CD3-CD19+CD20-CD38+, CD3-CD19+CD20-CD38+IgM+, and CD3-CD19+CD20-CD38+CD138+ B cells were larger in patients with IgAV than in the HCs. Only CD3-CD19+IgD-CD27+IgM+ B cell counts were reduced in IgAV. The elevated B cell numbers returned to normal after treatment. Plasma and plasmablast B cell numbers correlated with plasma IgA levels. On the contrary, CD3-CD19+IgD-CD27+IgM+ B cell numbers were negatively proportional to the plasma IgA levels while naïve B cell numbers correlated with plasma and plasmablast B cell counts.ConclusionsWe hypothesized that immunoglobulin production was abnormally elevated in IgAV and could be explained by altered B-cell subset homeostasis.

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