Antibodies targeting protein-arginine deiminase 4 (PAD4) demonstrate diagnostic value in rheumatoid arthritis

Martinez-Prat, Laura; Lucia, David; Ibarra, Claudia; Mähler, Michael; Dervieux, Thierry

doi:10.1136/annrheumdis-2018-213818

Cited by 22 publications

(26 citation statements)

References 6 publications

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“…Peptidylarginine deiminases (PADs) are enzymes that catalyze the deimino production of arginine residues in protein peptide chains to produce citrulline residues, including 5 subtypes, of which only PAD4 can exist in the nucleus 54 and is closely related to the pathogenesis and susceptibility of RA. The study found that the level of PAD4 protein in serum, articular synovial F I G U R E 3 Abnormal activation of T cells and B cells, bone resorption, cartilage destruction and angiogenesis tissue, and peripheral blood neutrophils of RA patients is high, [55][56][57][58][59] and anti-PAD4 antibody can also be used as a clinical diagnostic indicator of RA, [60][61][62] and the level in patients can be maintained in long-term stability. 63 However, after TNF-α stimulated HL-60 cells to activate NF-κB, the expression of PAD4 decreased.…”

Section: Anti-inflammatory Pathologymentioning

confidence: 99%

Nuclear factor‐κB in rheumatoid arthritis

Tang

Shi

et al. 2020

Int J of Rheum Dis

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NF-κB (nuclear factor kappa light chain enhancer of activated B cells) signaling pathway is involved in the occurrence and development of various kinds of inflammation, including rheumatoid arthritis (RA). In this paper, the relationship between the activation or inhibition of NF-κB and the pathogenesis of RA is discussed. It is found that activated NF-κB operates a dual-aspect effect which can either promote or suppress inflammation. When NF-κB is inhibited, the symptoms of RA are significantly improved. The specific role of NF-κB is closely related to its upstream stimulator and downstream activator. Therefore, we review the research on NF-κB in RA over the past 20 years in order to have a clearer understanding of its mechanism.

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Section: Anti-inflammatory Pathologymentioning

confidence: 99%

Nuclear factor‐κB in rheumatoid arthritis

Tang

Shi

et al. 2020

Int J of Rheum Dis

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“…The significance of anti-PAD4 in RA is still discussed. Laura Martinez-Prat et al have analyzed anti-PAD4 in a large cohort of 1473 RA patients and found its discriminative value between RA and HC especially in early RA [ 36 ]. Guderud et al recently showed different results and conclusions that anti-PAD4 is a bystander autoantibody [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis

Kolarz

Cieśla

Dryglewska

et al. 2020

JCM

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Protein citrullination is carried out by peptidylarginine deiminase type 4 (PAD4) enzyme. As a consequence of this process, post-translationally modified proteins are formed that become antigens for anti-citrullinated protein antibodies (ACPA). The study aimed at identifying whether the PADI4 gene is subject to epigenetic regulation through methylation of its promoter region, whether the degree of methylation differs in healthy individuals vs. rheumatoid arthritis (RA) patients and changes in correlation with ACPA, anti-PAD4 and disease activity. A total of 125 RA patients and 30 healthy controls were enrolled. Quantitative real-time methylation-specific PCR was used to analyze the methylation status. ACPA and anti-PAD4 antibodies were determined in serum by enzyme-linked immunosorbent immunoassay. The differences were observed in the degree of PADI4 gene promoter methylation between RA patients and HC, along with an upward trend for the methylation in RA, which was inversely proportional to the disease activity. A weak or modest negative correlation between the degree of PADI4 gene methylation and anti-PAD4, disease activity score (DAS28) and ACPA level has been found. The elevated methylation is associated with lower disease activity, lower levels of ACPA and aPAD4. The methylation degree in this area is growing up during effective treatment and might play a role in the RA pathophysiology and therefore could be a future therapeutic target.

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“…Следует подчеркнуть, что, как и другие аутоантитела, анти-ПАД4 могут выявляться до клинической манифестации РА. При этом чаще серопозитивны по анти-ПАД4 пациенты с «развернутым» РА (29-35%), чем с «ранним» (16-18%) [50,51,52]; анти-ПАД4 чаще обнаруживаются у АЦЦП-позитивных, чем у АЦЦП-негативных пациентов [53,54]. Однако, по данным L. Martinez-Pra и соавт.…”

Section: антитела к пептидил-аргининдезаминазе (анти-пад)unclassified

“…Однако, по данным L. Martinez-Pra и соавт. [51], у АЦЦП-негативных пациентов чувствительность обнаружения анти-ПАД4 составляет 19,2%, специфичность -96,2%. Отмечена связь между выявлением анти-ПАД4 и рентгенологическим прогрессированием РА [55].…”

Section: антитела к пептидил-аргининдезаминазе (анти-пад)unclassified

New laboratory biomarkers of rheumatoid arthritis

Dibrov¹

2021

Naučno-praktičeskaâ revmatologiâ

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The review presents data on new biomarkers for the diagnosis of rheumatoid arthritis, considers the diagnostic parameters of antibodies to carbamylated proteins, antibodies to peptidyl arginine deaminase, antibodies to homocysteinylated α1-antitrypsin, 14-3-3η, macrophage soluble scavenger receptor A. The use of new biomarkers can improve the diagnosis of RA in the early stages, as well as stratify patients based on the prognosis of the disease and provide a rational selection of therapy.

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Antibodies targeting protein-arginine deiminase 4 (PAD4) demonstrate diagnostic value in rheumatoid arthritis

Cited by 22 publications

References 6 publications

Nuclear factor‐κB in rheumatoid arthritis

Nuclear factor‐κB in rheumatoid arthritis

Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis

New laboratory biomarkers of rheumatoid arthritis

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