Evidence map›Paper›PMID 35244943›Full record

ReviewPeriodontology 20002022

Maladaptive trained immunity and clonal hematopoiesis as potential mechanistic links between periodontitis and inflammatory comorbidities.

George Hajishengallis, Xiaofei Li, Kimon Divaris, Triantafyllos Chavakis

Open access · greenAbstract readReview
In one paragraph

Review in Periodontology 2000, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

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  20. [Role of Trained Immunity in the Association Between Periodontitis and Rheumatoid Arthritis].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 2 countries.

George HajishengallisDepartment of Basic and Translational Sciences, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Xiaofei LiDepartment of Basic and Translational Sciences, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kimon DivarisDivision of Pediatrics and Public Health, Adams School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
Triantafyllos ChavakisInstitute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
University of Pennsylvania · USTU Dresden · DEUniversity of North Carolina at Chapel Hill · US

Funding

Genome-Wide Association Study of Early Childhood CariesU01DE025046 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DIVARIS, KIMON · 2015 to 2019
$8.4M
Local endogenous regulators of functional immune plasticity in the periodontiumR37DE026152 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI HAJISHENGALLIS, GEORGIOS · 2016 to 2025
$3.5M
Neutrophil homeostasis and periodontitis: Novel concepts and treatmentsR01DE024153 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI HAJISHENGALLIS, GEORGIOS · 2016 to 2020
$2.0M
IL-22, Immune Plasticity, and Autotherapy in the PeriodontiumR01DE029436 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI HAJISHENGALLIS, GEORGIOS · 2020 to 2024
$1.9M
Trained innate immunity and periodontitis-associated comorbiditiesR01DE031206 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI Georgios Hajishengallis · 2022 to 2026
$1.9M
Aging and dysfunction of progenitor niches: Role of Del-1R01DE028561 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI HAJISHENGALLIS, GEORGIOS · 2020 to 2024
$1.7M
NIDCR NIH HHS R01 DE024153NIDCR NIH HHS R01 DE028561NIDCR NIH HHS R01 DE029436NIDCR NIH HHS R01 DE031206NIDCR NIH HHS R37 DE026152NIDCR NIH HHS U01 DE025046
6 · The paper itself

Abstract

Periodontitis is bidirectionally associated with systemic inflammatory disorders. The prevalence and severity of this oral disease and linked comorbidities increases with aging. Here, we review two newly emerged concepts, trained innate immunity (TII) and clonal hematopoiesis of indeterminate potential (CHIP), which together support a potential hypothesis on how periodontitis affects and is affected by comorbidities and why the susceptibility to periodontitis and comorbidities increases with aging. Given that chronic diseases are largely triggered by the action of inflammatory immune cells, modulation of their bone marrow precursors, the hematopoietic stem and progenitor cells (HSPCs), may affect multiple disorders that emerge as comorbidities. Such alterations in HSPCs can be mediated by TII and/or CHIP, two non-mutually exclusive processes sharing a bias for enhanced myelopoiesis and production of innate immune cells with heightened proinflammatory potential. TII is a state of elevated immune responsiveness based on innate immune (epigenetic) memory. Systemic inflammation can initiate TII in the bone marrow via sustained rewiring of HSPCs, which thereby display a skewing toward the myeloid lineage, resulting in generation of hyper-reactive or "trained" myeloid cells. CHIP arises from aging-related somatic mutations in HSPCs, which confer a survival and proliferation advantage to the mutant HSPCs and give rise to an outsized fraction of hyper-inflammatory mutant myeloid cells in the circulation and tissues. This review discusses emerging evidence that supports the notion that TII and CHIP may underlie a causal and age-related association between periodontitis and comorbidities. A holistic mechanistic understanding of the periodontitis-systemic disease connection may offer novel diagnostic and therapeutic targets for treating inflammatory comorbidities.

Indexed as

Clonal HematopoiesisPeriodontitisHematopoietic Stem CellsHumansImmunity, InnateInflammationagingclonal hematopoiesiscomorbiditieshematopoietic stem cellsperiodontitistrained immunity

Identifiers

PMID35244943
PMCPMC9018499
OpenAlexW4214873340

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.