Evidence map›Paper›PMID 31262358›Full record

ArticleArthritis research & therapy2019

Anti-D4GDI antibodies activate platelets in vitro: a possible link with thrombocytopenia in primary antiphospholipid syndrome.

C Barbati, L Stefanini, T Colasanti, E Cipriano, A Celia, G Gabriele, M Vomero, F Ceccarelli, F R Spinelli, A Finucci and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 38% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. 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

18 authors at 2 institutions in 1 country.

C BarbatiDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy. cristiana.barbati1@gmail.com.ORCID 0000-0003-4121-5342
L StefaniniDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
T ColasantiDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
E CiprianoDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
A CeliaDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
G GabrieleDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
M VomeroDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
F CeccarelliDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
F R SpinelliDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
A FinucciDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
M SpezialiDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
G OrsoDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
D P E MargiottaDepartment of Immuno-Rheumatology, Campus Bio-Medico, University of Rome, Rome, Italy.
F ContiDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
F VioliDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
A AfeltraDepartment of Immuno-Rheumatology, Campus Bio-Medico, University of Rome, Rome, Italy.
G ValesiniDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
C AlessandriDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico, 155, Rome, Italy.
Policlinico Umberto I · ITUniversità Campus Bio-Medico · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThrombocytopenia is a manifestation associated with primary antiphospholipid syndrome (PAPS), and many studies have stressed the leading role played by platelets in the pathogenesis of antiphospholipid syndrome (APS). Platelets are highly specialized cells, and their activation involves a series of rapid rearrangements of the actin cytoskeleton. Recently, we described the presence of autoantibodies against D4GDI (Rho GDP dissociation inhibitor beta, ARHGDIB) in the serum of a large subset of SLE patients, and we observed that anti-D4GDI antibodies activated the cytoskeleton remodeling of lymphocytes by inhibiting D4GDI and allowing the upregulation of Rho GTPases, such as Rac1. Proteomic and transcriptomic studies indicate that D4GDI is very abundant in platelets, and small GTPases of the RHO family are critical regulators of actin dynamics in platelets.

methodsWe enrolled 38 PAPS patients, 15 patients carrying only antiphospholipid antibodies without clinical criteria of APS (aPL carriers) and 20 normal healthy subjects. Sera were stored at - 20 °C to perform an ELISA test to evaluate the presence of anti-D4GDI antibodies. Then, we purified autoantibodies anti-D4GDI from patient sera. These antibodies were used to conduct in vitro studies on platelet activation.

resultsWe identified anti-D4GDI antibodies in sera from 18/38 (47%) patients with PAPS, in sera from 2/15(13%) aPL carriers, but in no sera from normal healthy subjects. Our in vitro results showed a significant 30% increase in the activation of integrin αIIbβ3 upon stimulation of platelets from healthy donors preincubated with the antibody anti-D4GDI purified from the serum of APS patients.

conclusionsIn conclusion, we show here that antibodies anti-D4GDI are present in the sera of PAPS patients and can prime platelet activation, explaining, at least in part, the pro-thrombotic state and the thrombocytopenia of PAPS patients. These findings may lead to improved diagnosis and treatment of APS.

Indexed as

Antibodies, AntiphospholipidAntiphospholipid SyndromeAutoantibodiesBiomarkersBlood PlateletsEnzyme-Linked Immunosorbent AssayFollow-Up StudiesHumansPlatelet ActivationProteomicsRetrospective StudiesThrombocytopeniaAntibodies, AntiphospholipidAutoantibodiesBiomarkersD4GDIPlateletsPrimary antiphospholipid syndromeRho GTPases

Identifiers

PMID31262358
PMCPMC6604387
OpenAlexW2954360545

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LicenceCC BY
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Registered trials

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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.