scholarly journals Altered B cell compartment associated with Tfh cells in children with Henoch-Schonlein Purpura

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ning Zhang ◽  
Ge Tian ◽  
Yuanyuan Sun ◽  
Jing Pan ◽  
Wei Xu ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Mononuclear Cells ◽  
Absolute Number ◽  
Henoch Schonlein Purpura ◽  
Cell Compartment ◽  
Tfh Cells ◽  
B Cell Subsets ◽  
Schonlein Purpura ◽  
Henoch Schönlein Purpura

Abstract Aim IgA-producing B cells have been found to be associated with children diagnosed with Henoch-Schonlein purpura (HSP). The aim of the present study was to determine whether children with HSP possess altered B-cell subsets. Methods A total of 14 children diagnosed with HSP and age- and sex-matched healthy controls (HCs) were enrolled in our study. Peripheral blood mononuclear cells were isolated, and the percentage and absolute number of B-cell subsets and Follicular helper T (Tfh) cells were determined by flow cytometry. Finally, Spearman’s correlation coefficient was used to analyse the correlation between the percentage of Tfh cells and B-cell subsets. Results We found that compared to HCs, the frequency and absolute number of total B cells were significantly higher in children with HSP, but the percentages of plasma cells and naïve B cells were significantly lower. A significantly increased percentage and absolute number of memory nonswitched B cells were found in children with HSP compared with HCs. We observed that the expression of C-X-C chemokine receptor type 5 (CXCR5) on total CD4+ T cells and the percentage of CD4+CXCR5+ cells were significantly increased in patients with HSP. Moreover, significantly correlations between Tfh cells and various B-cell subsets were observed. Conclusions Our study showed a Tfh-cell-associated altered B cell compartment in children with HSP.

scholarly journals Abnormal B Cell Compartment Associated With Tfh Cells in Children With Henoch-schonlein Purpura

2020 ◽  
Author(s):  
Ning Zhang ◽  
Ge Tian ◽  
Yuanyuan Sun ◽  
Jing Pan ◽  
Wei Xu ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Henoch Schonlein Purpura ◽  
Cell Compartment ◽  
Tfh Cells ◽  
B Cell Subsets ◽  
Schonlein Purpura ◽  
Henoch Schönlein Purpura

Abstract Aim IgA-producing B cells were found to be associated with children diagnosed with Henoch-Schonlein purpura (HSP). The present study aimed to determine whether children with HSP possess abnormal B cell subsets. Methods A total of 14 children diagnosed with HSP, and age- and gender-matched healthy controls were enrolled in our study. Peripheral blood mononuclear cells were isolated, and the percentage of B cells subsets and Tfh cells were determined by flow cytometry. Finally, Spearman’s correlation coefficient was used to analyze the correlation between the percentage of Tfh cells and B cell subsets. Results We found that the frequency of total B cells was significantly increased in children with HSP; however, the percentage of plasma cells was significantly lower in HSP children. A significant reduction in the count of naïve B cells and an increase in class-switched B cells were found in children with HSP compared with healthy controls. We observed that the expression of C-X-C chemokine receptor type 5 (CXCR5) on total CD4+ T cells and the percentage of CD4+CXCR5+ cells were significantly increased within HSP patients. Moreover, significant correlations between Tfh cells and various B cells subsets were observed. Conclusion Our study showed a Tfh cell-associated abnormal B cell compartment in HSP children.

scholarly journals OP0024 DECREASED LEVELS OF T FOLLICULAR HELPER (CD4+CXCR5+) CELLS AND CD27+CD38+ AND CD27+CD38- B CELLS IN ANKYLOSING SPONDYLITIS PATIENTS CORRELATE WITH MARKER OF INFLAMMATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 13.2-14
Author(s):  
H. Forsblad-D’elia ◽  
U. Hellman ◽  
A. Kumar ◽  
K. Lejon
Keyword(s):  
Ankylosing Spondylitis ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Female Patients ◽  
Tfh Cells ◽  
Follicular Helper ◽  
B Cell Subsets

Background:The role of different lymphocyte subsets in ankylosing spondylitis (AS) is still to be elucidated. It has previously been reported contradictory data concerning the levels of T Follicular Helper (TFH) cells and differentiated B cells in peripheral blood of AS patients. In addition, the connection to disease related parameters is still to be fully revealed.Objectives:The purpose of this study was to investigate the level of CD4+TFH cells and CD27+CD38+/CD38- B cells in patients with AS from northern Sweden and to compare the levels with age and sex-matched controls. We also studied associations between these cell subsets and disease related factors.Methods:Peripheral blood mononuclear cells (PBMSc) from a cohort of 50 patients with AS from Region Västerbotten (mean age 52±9.1 years, 33 (66 %) men, 50 (100 %) HLAB27 positive) and 50 pair wise matched blood donor controls (mean age 54±8.8 years, 33 (66 %) men) were stained with a combination of antibodies allowing for the detection of CD27, CD38, CD19, CD3, CD4 and CXCR5 markers and analyzed by flow cytometry. In addition, the patient with AS were examined with spinal x-ray for radiographic alterations assessed with mSASSS. CRP and ESR were measured and physical function and disease activity were registered with BASMI and BASFI respectively ASDAS-CRP and BASDAI.Results:When comparing AS patients and controls pair wise, we observed on average a 50% reduction of TFH (CD3+CD4+CXCR5+) cells among CD45+ lymphocytes in PBMCs from patients (p=0,000008). Furthermore, a 20-30% reduction among memory/plasma cells (CD19+CD27+CD38+ and CD19+CD27+CD38-) among CD45+ lymphocytes in PBMCs from patients (p=0,002 and p=0,007 respectively). For female patients a correlation between TFH and ESR (Rs=-0,551 p=0,022) was observed. Moreover, negative correlations between the two B cell subsets (CD19+CD27+CD38+ and CD19+CD27+CD38-) and ESR were observed for female patients (Rs =–0,476 p=0,053 and Rs =–0,522 p=0,032 respectively).Conclusion:TFH cells was reduced in AS patients and this reduction correlated with a reduction in differentiated (CD27+CD38+ and CD27+CD38-) B cells. In addition, the inflammation marker ESR was negatively correlated with TFH as well as with the differentiated B cell subsets in female patients. Our observations indicates a role of the humoral immune response in AS.Disclosure of Interests:None declared

scholarly journals Elevated STAT1 expression but not phosphorylation in lupus B cells correlates with disease activity and increased plasmablast susceptibility

Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3435-3442 ◽  
Author(s):  
Arman Aue ◽  
Franziska Szelinski ◽  
Sarah Y Weißenberg ◽  
Annika Wiedemann ◽  
Thomas Rose ◽  
...  
Keyword(s):  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Mononuclear Cells ◽  
Janus Kinase ◽  
T Cell Subsets ◽  
Type I ◽  
Type I Ifn ◽  
Peripheral Blood Mononuclear ◽  
B Cell Subsets

Abstract Objectives SLE is characterized by two pathogenic key signatures, type I IFN and B-cell abnormalities. How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT). JAK-STAT inhibition is an attractive therapeutic possibility for SLE. We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared with other autoimmune diseases and healthy controls (HD) and related it to disease activity. Methods Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T cells of 21 HD, 10 rheumatoid arthritis (RA), seven primary Sjögren’s (pSS) and 22 SLE patients was analysed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs (peripheral blood mononuclear cells) of SLE patients and HD after IFNα and IFNγ incubation were further investigated. Results SLE patients showed substantially higher STAT1 but not pSTAT1 in B- and T-cell subsets. Increased STAT1 expression in B-cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker. STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ. Conclusion Enhanced expression of STAT1 by B-cell candidates as a key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold a promise to block STAT1 expression and control plasmablast induction in SLE.

scholarly journals Complexity of the human memory B-cell compartment is determined by the versatility of clonal diversification in germinal centers

2015 ◽  
Vol 112 (38) ◽  
pp. E5281-E5289 ◽  
Author(s):  
Bettina Budeus ◽  
Stefanie Schweigle de Reynoso ◽  
Martina Przekopowitz ◽  
Daniel Hoffmann ◽  
Marc Seifert ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Clone ◽  
Human Memory ◽  
Memory B Cells ◽  
Sequencing Analysis ◽  
Cell Compartment ◽  
Memory B Cell ◽  
Cell Clones ◽  
B Cell Subsets

Our knowledge about the clonal composition and intraclonal diversity of the human memory B-cell compartment and the relationship between memory B-cell subsets is still limited, although these are central issues for our understanding of adaptive immunity. We performed a deep sequencing analysis of rearranged immunoglobulin (Ig) heavy chain genes from biological replicates, covering more than 100,000 memory B lymphocytes from two healthy adults. We reveal a highly similar B-cell receptor repertoire among the four main human IgM+ and IgG+ memory B-cell subsets. Strikingly, in both donors, 45% of sequences could be assigned to expanded clones, demonstrating that the human memory B-cell compartment is characterized by many, often very large, B-cell clones. Twenty percent of the clones consisted of class switched and IgM+(IgD+) members, a feature that correlated significantly with clone size. Hence, we provide strong evidence that the vast majority of Ig mutated B cells—including IgM+IgD+CD27+ B cells—are post-germinal center (GC) memory B cells. Clone members showed high intraclonal sequence diversity and high intraclonal versatility in Ig class and IgG subclass composition, with particular patterns of memory B-cell clone generation in GC reactions. In conclusion, GC produce amazingly large, complex, and diverse memory B-cell clones, equipping the human immune system with a versatile and highly diverse compartment of IgM+(IgD+) and class-switched memory B cells.

scholarly journals Association between Tfh and PGA in children with Henoch–Schönlein purpura

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 986-991
Author(s):  
Miao Meihua ◽  
Li Xiaozhong ◽  
Wang Qin ◽  
Zhu Yunfen ◽  
Cui Yanyan ◽  
...  
Keyword(s):  
Respiratory Infection ◽  
Acute Respiratory Infection ◽  
Elective Surgery ◽  
Significant Elevation ◽  
Henoch Schonlein Purpura ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Schonlein Purpura ◽  
Increased Activity ◽  
Henoch Schönlein Purpura

Abstract Objective The aim of this study was to investigate the roles of follicular helper CD4+ T cells (Tfh) and serum anti-α-1,4-d-polygalacturonic acid (PGA) antibody in the pathogenesis of Henoch–Schönlein purpura (HSP). Methods ELISA was performed to determine serum PGA-IgA and PGA-IgG. Flow cytometry was utilized to determine the peripheral CD4+ CXCR5+ and CD4+ CXCR5+ ICOS+ Tfh cells. Real-time PCR was conducted to determine the expression of Bcl-6 gene. Then the change of Tfh cells was analyzed, together with the association with the anti-PGA antibody as well as the roles in the pathogenesis of HSP. Results Compared with the cases with acute respiratory infection and elective surgery, the proportion of CD4+ CXCR5+ and CD4+ CXCR5+ ICOS+ Tfh cells in the HSP group showed significant elevation (P < 0.001). A significant correlation was noticed between PGA-IgA and CD4+ CXCR5+ Tfh cells (r = 0.380 and P = 0.042) and CD4+ CXCR5+ ICOS+ Tfh cells (r = 0.906 and P < 0.001). The expression of Bcl-6 in the HSP group showed no statistical difference compared with that in the acute respiratory infection and the surgery control (P < 0.05). Conclusion Increased activity of Tfh cells, which is closely related to mucosal immunity, may be a major contributor in the elevation of PGA-IgA, and Tfh cells and PGA-IgA are closely related to the occurrence of HSP.

scholarly journals Intrathecal B-cell activation in LGI1 antibody encephalitis

2020 ◽  
Vol 7 (2) ◽  
pp. e669 ◽  
Author(s):  
Klaus Lehmann-Horn ◽  
Sarosh R. Irani ◽  
Shengzhi Wang ◽  
Arumugam Palanichamy ◽  
Sarah Jahn ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Cell Activity ◽  
Oligoclonal Bands ◽  
B Cell Activation ◽  
Cell Repertoire ◽  
Antibody Titers ◽  
B Cell Subsets

ObjectiveTo study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant LGI1 antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within the CNS contribute to the ongoing pathogenesis of LGI1 antibody encephalitis.MethodsPaired CSF and peripheral blood (PB) mononuclear cells were collected from 6 patients with LGI1 antibody encephalitis and 2 patients with other neurologic diseases. Deep B-cell immune repertoire sequencing was performed on immunoglobulin heavy chain transcripts from CSF B cells and sorted PB B-cell subsets. In addition, LGI1 antibody levels were determined in CSF and PB.ResultsSerum LGI1 antibody titers were on average 127-fold higher than CSF LGI1 antibody titers. Yet, deep B-cell repertoire analysis demonstrated a restricted CSF repertoire with frequent extensive clusters of clonally related B cells connected to mature PB B cells. These clusters showed intensive mutational activity of CSF B cells, providing strong evidence for an independent CNS-based antigen-driven response in patients with LGI1 antibody encephalitis but not in controls.ConclusionsOur results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies.

scholarly journals Jo-1 autoantigen-specific B cells are skewed towards distinct functional B cell subsets in anti-synthetase syndrome patients

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jennifer Young-Glazer ◽  
Alberto Cisneros ◽  
Erin M. Wilfong ◽  
Scott A. Smith ◽  
Leslie J. Crofford ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Biology ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Cell Subset ◽  
Trna Synthetase ◽  
B Cell Subsets ◽  
Antibody Secreting Cells

Abstract Background Anti-Jo-1 autoantibodies which recognize histidyl-tRNA synthetase identify patients with the rare rheumatologic disease, anti-histidyl-tRNA synthetase syndrome (Jo-1 ARS), a phenotypically distinct subset of idiopathic inflammatory myopathies (IIM). Jo-1-binding B cells (JBCs) are implicated in disease pathogenesis, yet they have not been studied directly. We therefore aimed to characterize JBCs to better understand how they expand and function in Jo-1 ARS. Methods We enrolled 10 IIM patients diagnosed with Jo-1 ARS, 4 patients with non-Jo-1 IIM, and 8 age- and sex-matched healthy controls. We phenotypically characterized peripheral blood mononuclear cells (PBMCs) ex vivo using flow cytometry to define the B cell subsets in which JBCs reside. We further tested their ability to differentiate into antibody-secreting cells following stimulation in vitro. Results The majority of JBCs were IgM+ (not class-switched). Compared to non-JBCs in the same donors, JBCs contained a higher percentage of autoimmune-prone CD21lo cells and were increased in the CD21lo IgM+ IgD− CD27+ memory subset relative to healthy donor B cells. Whereas non-JBCs were present in the anergic BND B cell subset, JBCs were nearly absent from this compartment. JBCs were detected among plasmablasts in some donors, but a reduced frequency of JBCs differentiated into CD38hi24− plasmablasts compared to non-JBCs present in the same wells following in vitro stimulation. Conclusions JBCs are enriched for autoimmune-prone CD21lo B cells, some of which exhibit a memory phenotype in the peripheral repertoire of Jo-1 ARS patients. JBCs undergo limited class switch and show reduced capacity to differentiate into antibody-secreting cells. This suggests complex B cell biology exists beyond class-switched cells that differentiate to secrete anti-Jo-1 autoantibody (i.e., what is captured through serum autoantibody studies). New Jo-1 ARS therapies should thus ideally target non-class-switched JBCs in addition to those that have undergone IgG class-switching to most effectively block cross-talk with autoreactive T cells.

scholarly journals Remission Induced by TNF Inhibitors Plus Methotrexate is Associated With Changes in Peripheral Naïve B Cells in Patients With Rheumatoid Arthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Borja Hernández-Breijo ◽  
Chamaida Plasencia-Rodríguez ◽  
Victoria Navarro-Compán ◽  
Carlota García-Hoz ◽  
Israel Nieto-Gañán ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
Mononuclear Cells ◽  
Tnf Inhibitors ◽  
Concomitant Therapy ◽  
Peripheral Blood Mononuclear ◽  
Logistic Regression Models ◽  
Cell Percentage ◽  
B Cell Subsets

Biological therapies, such as TNF inhibitors (TNFi), are increasing remission (REM) rates in rheumatoid arthritis (RA) patients, although these are still limited. The aim of our study was to analyze changes in the profile of peripheral blood mononuclear cells (PBMC) in patients with RA treated with TNFi in relation to the clinical response. This is a prospective and observational study including 78 RA patients starting the first TNFi. PBMC were analyzed by flow cytometry both at baseline and at 6 months. Disease activity at the same time points was assessed by DAS28, establishing DAS28 ≤ 2.6 as the criteria for REM. Logistic regression models were employed to analyze the association between the changes in PBMC and REM. After 6 months of TNFi treatment, 37% patients achieved REM by DAS28. Patients who achieved REM showed a reduction in the percentage of naive B cells, but only when patients had received concomitant methotrexate (MTX) (OR: 0.59; 95% CI: 0.39–0.91). However, no association was found for patients who did not receive concomitant MTX (OR: 0.85; 95% CI: 0.63–1.16). In conclusion, PBMC, mainly the B-cell subsets, are modified in RA patients with TNFi who achieve clinical REM. A significant decrease in naive B-cell percentage is associated with achieving REM after 6 months of TNFi treatment in patients who received concomitant therapy with MTX.

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