ACPA-positive versus ACPA-negative rheumatoid arthritis: two distinct erosive disease entities on radiography and ultrasonography

Grosse, J.; Allado, Edem; Roux, C.; Pierreisnard, A.; Couderc, Marion; Clerc‐Urmès, Isabelle; Rémen, Thomas; Albuisson, Éliane; Bittencourt, Marcelo De Carvalho; Chary‐Valckenaere, Isabelle; Lœuille, Damien

doi:10.1007/s00296-019-04492-5

Cited by 26 publications

(20 citation statements)

References 59 publications

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“…Variables associated with joint erosion on the modi ed Sharp-Van der Heijde erosion score in univariate analysis were the presence of ACPA, RF and double positivity. These relations are already known and previously reported in the literature (7) .…”

Section: Discussionsupporting

confidence: 80%

The Role of Autoimmunity on the Relation Between Erosions and Bone Mineral Density in Rheumatoid Arthritis: A Clinical Research

Moret

Morizot

Bittencourt

et al. 2021

Preprint

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IntroductionBoth erosions and osteoporosis are present in rheumatoid arthritis and are related to RANK-L pathway activation. The aim of the study was to evaluate the relationship between erosion and bone mineral density (BMD) in RA and whether it can be driven by autoimmunity.Patients and methodsPatients followed in the Department of Rheumatology between January 2008 and May 2019 satisfied the 1987 ACR or 2010 ACR-EULAR criteria. Erosions were evaluated by the modified Sharp/van der Heidje erosion score (SHSe) on radiographs and bone mineral density (BMD) in g/cm2 and by the T-score at the hip on DXA. The presence and titers of ACPA as well as rheumatoid factor (RF) and anti-nuclear antibodies (ANAs) were recorded at intervals of less than 2 years for both DXA and radiography.ResultsA total of 149 patients met the inclusion criteria. A total of 61.1% were ACPA positive, 79.9% were erosive and 10.7% had a hip T-score ≤-2.5. ACPA status but not titers was associated with a higher erosion score (63.0 (53.2) for ACPA + vs. 45.5 (44.1) for ACPA – (p= 0.04)). ACPA titers were associated with lower BMD at the hip (value -0.216; p=0.01) but not with T-score. A higher erosion score was associated with a lower BMD (R2: 0,049 and value: -0.222; p=0.009) and T-score (R2: 0,158 and value -0.397; p<0.0001) at the hip. In linear regression, erosion and systemic bone loss were still associated with but not driven by ACPA status or titer. RF and ANA did not demonstrate any role in this association.ConclusionWe showed that the relationship between erosion and bone mineral density associated with RA does not seem to be driven by ACPA or other autoimmunity parameters. However, the presence of ACPA or erosion should lead to osteoporosis assessment.

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Section: Discussionsupporting

confidence: 80%

The Role of Autoimmunity on the Relation Between Erosions and Bone Mineral Density in Rheumatoid Arthritis: A Clinical Research

Moret

Morizot

Bittencourt

et al. 2021

Preprint

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“…The process of citrullination and the role of autoantibodies against these modified antigens is of special interest in RA. ACPA production is promoted by environmental factors like smoking and genetic predispositions such as HLA-DRB1 [ 36 ]. Several studies reported that ACPA positive patients are prone to have more joint erosions [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…ACPA production is promoted by environmental factors like smoking and genetic predispositions such as HLA-DRB1 [ 36 ]. Several studies reported that ACPA positive patients are prone to have more joint erosions [ 36 , 37 ]. ACPA form immune complexes with the citrullinated peptides leading to the activation of macrophages and proinflammatory cytokine production, as well as osteoclastogenesis [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies reported that ACPA positive patients are prone to have more joint erosions [ 36 , 37 ]. ACPA form immune complexes with the citrullinated peptides leading to the activation of macrophages and proinflammatory cytokine production, as well as osteoclastogenesis [ 36 , 37 ]. ACPA is highly specific to RA and can be early detected, even before the onset of RA.…”

Section: Discussionmentioning

confidence: 99%

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Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca2+ Influx in Nkx2-3 Knock-out Mice

Khanfar

Olasz

Gábris

et al. 2020

IJMS

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B cells play a crucial role in the pathogenesis of rheumatoid arthritis. In Nkx2-3-deficient mice (Nkx2-3−/−) the spleen’s histological structure is fundamentally changed; therefore, B cell homeostasis is seriously disturbed. Based on this, we were curious, whether autoimmune arthritis could be induced in Nkx2-3−/− mice and how B cell activation and function were affected. We induced arthritis with immunization of recombinant human proteoglycan aggrecan G1 domain in Nkx2-3−/− and control BALB/c mice. We followed the clinical picture, characterized the radiological changes, the immune response, and intracellular Ca2+ signaling of B cells. Incidence of the autoimmune arthritis was lower, and the disease severity was milder in Nkx2-3−/− mice than in control BALB/c mice. The radiological changes were in line with the clinical picture. In Nkx2-3−/− mice, we measured decreased antigen-induced proliferation and cytokine production in spleen cell cultures; in the sera, we found less anti-CCP-IgG2a, IL-17 and IFNγ, but more IL-1β, IL-4 and IL-6. B cells isolated from the lymph nodes of Nkx2-3−/− mice showed decreased intracellular Ca2+ signaling compared to those isolated from BALB/c mice. Our findings show that the transcription factor Nkx2-3 might regulate the development of autoimmune arthritis most likely through modifying B cell activation.

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“…48 High levels of ACPAs are associated with the development of bone erosion in patients with RA. 7,49 ACPAs may contribute to activating osteoclasts through their Fc glycan interactions with Fc receptors on osteoclasts to promote osteoclast activation and subsequent development of bone erosion, which is dependent on antibody-mediated effect. 50 RA-associated ILD frequently appears in patients with positive ACPA and cigarette smoking, but the specific mechanism of the underlying association between lung injury and ACPA generation remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of anti‐citrullinated α‐enolase peptide 1 antibody in patients with rheumatoid arthritis: A systematic review and meta‐analysis

Liu

et al. 2021

Int J of Rheum Dis

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ACPA-positive versus ACPA-negative rheumatoid arthritis: two distinct erosive disease entities on radiography and ultrasonography

Cited by 26 publications

References 59 publications

The Role of Autoimmunity on the Relation Between Erosions and Bone Mineral Density in Rheumatoid Arthritis: A Clinical Research

The Role of Autoimmunity on the Relation Between Erosions and Bone Mineral Density in Rheumatoid Arthritis: A Clinical Research

Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca2+ Influx in Nkx2-3 Knock-out Mice

Diagnostic value of anti‐citrullinated α‐enolase peptide 1 antibody in patients with rheumatoid arthritis: A systematic review and meta‐analysis

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