Evidence map›Paper›PMID 42120292›Full record

ArticleAnnals of the rheumatic diseases2026

Anti-PAD4 antibodies link autoimmunity to PAD4 with CTL-associated rheumatoid arthritis.

Kusuma Ananth, Katharine B Moosic, Eduardo Gomez-Banuelos, Hong Wang, Isabel Trejo-Zambrano, Ramona Johnson, Jessica Marie Kirschmann, Tess Deddens, Omar Elghawy, Bryna Shemo and 8 more

Abstract read
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In one paragraph

Article in Annals of the rheumatic diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

18 authors.

Kusuma AnanthDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Katharine B MoosicDivision of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
Eduardo Gomez-BanuelosDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hong WangDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Isabel Trejo-ZambranoDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ramona JohnsonDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jessica Marie KirschmannDivision of Immunology and Rheumatology, Stanford School of Medicine, Stanford, CA, USA; The Geriatric Research, Education, and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
Tess DeddensDivision of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
Omar ElghawyDivision of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
Bryna ShemoDivision of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
William H RobinsonDivision of Immunology and Rheumatology, Stanford School of Medicine, Stanford, CA, USA; The Geriatric Research, Education, and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
Donald KimpelDivision of Rheumatology & Immunology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
Clifton O BinghamDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
David J FeithDivision of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
Brendan AntiochosDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Felipe AndradeDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Thomas P LoughranDivision of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA. Electronic address: tl7cs@uvahealth.org.
Erika DarrahDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: edarrah1@jhmi.edu.

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
Sample Processing and Immunoassay Research CoreP30AR070254 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CLIFTON O BINGHAM, Antony Rosen · 2016 to 2026
$8.9M
Genomic Architecture of LGL LeukemiaR01CA178393 · NCI · UNIVERSITY OF VIRGINIA · PI Thomas P. Loughran, Aakrosh Ratan · 2016 to 2026
$6.5M
Phenotype-Specific Immune Responses in the Systemic VasculitidesP30AR053503 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI SOLOSKI, MARK J · 2006 to 2015
$6.4M
The role of cytotoxic T cells in rheumatoid arthritis pathogenesisR01AR079404 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI ANDRADE, FELIPE · 2021 to 2025
$2.9M
Insights into the origin of ACPAs in RAR21AI188438 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Felipe Andrade · 2025 to 2026
$421k
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA178393NIAID NIH HHS R21 AI188438NIAMS NIH HHS P30 AR053503NIAMS NIH HHS P30 AR070254NIAMS NIH HHS R01 AR079404
6 · The paper itself

Abstract

objectivesWe aimed to study the serologic, genetic, and immunologic underpinnings associated with cytotoxic T lymphocytes (CTLs) in rheumatoid arthritis (RA), using T-large granular lymphocytic leukaemia with comorbid RA (T-LGLL/RA) as a model of CTL-linked RA.

methodsWe used blood samples and paired clinical data from patients with RA, T-LGLL/RA, T-LGLL and healthy controls. Serological characterisation was performed using anti-cyclic citrullinated peptide 3.1 (anti-CCP3.1) enzyme-linked immunosorbent assay, multiplex RA autoantigen array, and radiolabelled peptidylarginine deiminase type III and IV (PAD4) immunoprecipitations. Genetic characterisation was performed using PADI4 single nucleotide polymorphism TaqMan genotyping assays and droplet digital polymerase chain reaction for signal transducer and activator of transcription 3 (STAT3) mutations. Multiparameter flow cytometry and pentamer binding assays were performed to immunophenotype CTLs and characterise PAD4-specific CTLs, respectively.

resultsPatients with T-LGLL/RA had enhanced anticitrullinated protein antibody responses compared with RA, and a strikingly higher frequency of anti-PAD4 antibodies (60% vs 27%, P < .0001). Among patients with T-LGLL, PADI4 single nucleotide polymorphisms were associated with anti-PAD4-positive RA (20% vs 3%, P = .02), and anti-PAD4 antibody levels were inversely correlated with absolute neutrophil count (Spearman's rho = -0.236; P = .02). Activating STAT3 mutations were associated with anti-PAD4 antibodies in both T-LGLL/RA (90% vs 74%, P = .047) and RA (39% vs 9%, P = .002). Flow cytometric characterisation of CTLs showed that anti-PAD4-positive RA was enriched for CD57+, CD7 low, T effector memory cells re-expressing CD45RA (TEMRA) CTLs. Furthermore, PAD4-specific CTLs were detected in anti-PAD4+ patients with RA and expressed elevated levels of CD69, CD57, and KLRG1, and a TEMRA phenotype.

conclusionsThese data demonstrate a mechanistic link between autoimmunity to PAD4 and CTL-associated disease in RA.

Indexed as

Arthritis, RheumatoidAutoantibodiesAutoimmunityHydrolasesT-Lymphocytes, CytotoxicAdultAgedAnti-Citrullinated Protein AntibodiesCase-Control StudiesFemaleHumansMaleMiddle AgedPolymorphism, Single NucleotideProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4Anti-Citrullinated Protein AntibodiesAutoantibodiesHydrolasesPADI4 protein, humanProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4STAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID42120292
PMCPMC13384482

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