Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood

Blanco, E; Pérez-Andrés, Martín; Arriba-Méndez, Sonia; Contreras-Sanfeliciano, Teresa; Criado, Ignacio; Pelák, Ondřej; Serra‐Caetano, Ana; Romero, Alfonso E.; Puig, Noemí; Remesal, Ana; Canizales, Juan Torres; López‐Granados, Eduardo; Kalina, Tomáš; Sousa, Ana E.; Zelm, Menno C. van; Burg, Mirjam van der; Dongen, Jacques J. M. van; Órfão, Alberto

doi:10.1016/j.jaci.2018.02.017

Cited by 215 publications

(249 citation statements)

References 69 publications

(95 reference statements)

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“…Interestingly, a progressive decrease in subsets of recently-produced thymic emigrants and naïve T-cells and total B-lymphocytes, together with progressive increase in (distinct subsets of) T-helper cells was found. These results confirm and extend on recently reported reference ranges and age-associated changes (32)(33)(34) and are critical for adequate interpretation of extended immunophenotypic profiles in children in the diagnostic work-up of primary immunodeficiencies and other immune disorders, as well as for monitoring immune therapies. Therefore, this is a very important paper in the field of clinical cytometry.…”

Section: Normal Lymphocyte Ranges In Children Blood Enumeration Of Blsupporting

confidence: 89%

“…A critical step in defining altered immune cell profiles is the definition of reference values. This is particularly true in children, due to the high dynamics observed after birth, particularly during the first years of life and the relatively limited number of cell populations (particularly within T‐cells) for which reference ranges have been established during childhood in the literature. Garcia‐Prat et al provide reference values for >30 lymphocyte, monocyte and dendritic cell subsets in blood, based on a cohort of 159 children with an age range of between 1 month and 18 years.…”

Section: Normal Lymphocyte Ranges In Children Bloodmentioning

confidence: 99%

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Órfão¹

2019

Cytometry Part B Clinical

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Section: Normal Lymphocyte Ranges In Children Blood Enumeration Of Blsupporting

confidence: 89%

Section: Normal Lymphocyte Ranges In Children Bloodmentioning

confidence: 99%

Issue Highlights – May 2019

Órfão¹

2019

Cytometry Part B Clinical

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“…The difference between younger SLE patients and age‐matched controls was more striking than in the total population. Although this age correlation does not have any immediately obvious explanation, it may be related to the decline in general humoral immunity with age , the group of young SLE patients with very active disease, or the typical presentation of SLE earlier in life and its slow decline in activity over time. As anti‐p40 reactivity was strongly increased in young SLE patients compared to young control subjects, this correlation is compatible with an early role of p40 immunogenicity in the pathogenesis of the disease.…”

Section: Discussionmentioning

confidence: 81%

High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus

Carter

LaCava

Taylor

et al. 2019

Arthritis & Rheumatology

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Objective Long interspersed nuclear element 1 (LINE‐1) encodes 2 proteins, the RNA binding protein p40 and endonuclease and reverse transcriptase (open‐reading frame 2p [ORF2p]), which are both required for LINE‐1 to retrotranspose. In cells expressing LINE‐1, these proteins assemble with LINE‐1 RNA and additional RNA binding proteins, some of which are well‐known autoantigens in patients with systemic lupus erythematosus (SLE). This study was undertaken to investigate whether SLE patients also produce autoantibodies against LINE‐1 p40. Methods Highly purified p40 protein was used to quantitate IgG autoantibodies in serum from 172 SLE patients and from disease controls and age‐matched healthy subjects by immunoblotting and enzyme‐linked immunosorbent assay (ELISA). Preparations of p40 that also contained associated proteins were analyzed by immunoblotting with patient sera. Results Antibodies reactive with p40 were detected in the majority of patients and many healthy controls. Their levels were higher in patients with SLE, but not those with systemic sclerosis, compared to healthy subjects (P = 0.01). Anti‐p40 reactivity was higher in patients during a flare than in patients with disease in remission (P = 0.03); correlated with the SLE Disease Activity Index score (P = 0.0002), type I interferon score (P = 0.006), decrease in complement C3 level (P = 0.0001), the presence of anti‐DNA antibodies (P < 0.0001) and anti‐C1q antibodies (P = 0.004), and current or past history of nephritis (P = 0.02 and P = 0.003, respectively); and correlated inversely with age (r = −0.49, P < 0.0001). SLE patient sera also reacted with p40‐associated proteins. Conclusion Autoantibodies reacting with LINE‐1 p40 characterize a population of SLE patients with severe and active disease. These autoantibodies may represent an early immune response against LINE‐1 p40 that does not yet by itself imply clinically significant autoimmunity, but may represent an early, and still reversible, step toward SLE pathogenesis.

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“…B cells were further phenotyped by 8-color panels to describe PreGC and PostGC development and by 12-color panel revealing the IgH-isotype expressing cells (53,54). A fully standardized system including instrument setup, sample preparation and data analysis was built in a stepwise manner to aid in diagnostics and translational research in PID.…”

Section: Existing Efforts To Achieve Reproducibilitymentioning

confidence: 99%

Reproducibility of Flow Cytometry Through Standardization: Opportunities and Challenges

Kalina

2019

Cytometry Pt A

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There is an agreement in the field that interlaboratory reproducibility of flow cytometry measurements as well as the whole studies might be improved by a consensual use of methodological approach. Typically, a consensus is made on a crucial markers needed in the immunostaining panel, sometimes on the particular fluorochrome conjugates and rarely on a complete set of methods for sample preparation. The term "standardization" is used to describe the complete set of methodical steps, while "harmonization" is used for partial agreement on the method. Standardization can provide a platform for improved reproducibility of cytometry results over prolonged periods of time, across different sites and across different instruments. For the purpose of structured discussion, several desired aims are described: common interpretation of the immunophenotype definition of a target subset, accurate quantification, reproducible pattern of a multicolor immunophenotype, and reproducible intensity of all measured parameters. An overview of how standardization was approached by several large consortia is provided: EuroFlow, The ONE Study, Human Immunology Project Consortium (HIPC), and several other groups. Their particular aims and the tools adopted to reach those aims are noted. How those standardization efforts were adopted in the field and how the resulting outcome was evaluated is reviewed. Multiple challenges in the instrument hardware design, instrument setup tools, reagent design, and quality features need to be addressed to achieve optimal standardization. Furthermore, the aims of different studies vary, and thus, the reasonable requirements for standardization differ. A framework of reference for the reasonable outcomes of different approaches is offered. Finally, it is argued that complete standardization is important not only for the reproducibility of measurements but also for education, for quality assessment and for algorithmic data analysis. The different standardized approaches can and in fact should serve as benchmarking reference tools for the development of future flow cytometry studies.

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Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood

Cited by 215 publications

References 69 publications

Issue Highlights – May 2019

Issue Highlights – May 2019

High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus

Reproducibility of Flow Cytometry Through Standardization: Opportunities and Challenges

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