The Specificity of Monoclonal Anti–Citrullinated Protein Antibodies: Comment on the Article by Steen et al

Holmdahl, Rikard

doi:10.1002/art.40758

Cited by 3 publications

(3 citation statements)

References 8 publications

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“…Given these considerations as well as notices of correction and retraction, current data indicate that the biological effects observed with the monoclonal antibodies appear unrelated to the recognition of citrulline as a critical determinant of specificity 5 6 25. Hence, other mechanisms, unrelated to the recognition of citrullinated antigens, must have contributed to the results obtained (figure 1).…”

Section: Issues In Experimental Design and Performancementioning

confidence: 64%

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Pathogenic effector functions of ACPA: Where do we stand?

Toes

Pisetsky

2019

Ann Rheum Dis

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Section: Issues In Experimental Design and Performancementioning

confidence: 64%

“…The debate on the role of ACPA has been extensive and has now entered a new phase with the publication of correction notes appearing in this issue1 2 of Annals of the Rheumatic (ARD ). These notes concern papers that appeared in the journal in 20163 4 and follow a retraction note and correspondence in other journals 5–7…”

Section: Introductionmentioning

confidence: 99%

Pathogenic effector functions of ACPA: Where do we stand?

Toes

Pisetsky

2019

Ann Rheum Dis

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“…Antigen-specific binding to citrullinated vimentin on osteoclasts (18,19), but also Fc receptor-mediated effects (30), were shown to trigger enhanced osteoclast differentiation in the context of autoantibodies, both explaining the link between broad-spectrum autoimmunity and bone loss. On the other hand, effects of preparations of monoclonal antibodies against citrullinated proteins have to be interpreted with some caution, since such preparations did not reveal activity against anti-citrullinated proteins (31)(32)(33). Notably, Fc-mediated effects on osteoclasts are sufficient to explain autoantibody-triggered bone loss in the predisease phase.…”

Section: Discussionmentioning

confidence: 99%

Microstructural Bone Changes Are Associated With Broad‐Spectrum Autoimmunity and Predict the Onset of Rheumatoid Arthritis

Simón

Kleyer

Bui

et al. 2022

Arthritis & Rheumatology

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Objective. To assess if microstructural bone lesions in individuals at risk of developing rheumatoid arthritis (RA) are related to the spectrum of anti-modified protein antibodies (AMPAs) and affect the risk of developing RA.Methods. Cortical microchannels as well as cortical and trabecular bone mineral density (BMD) volumes (expressed as mg hydroxyapatite/cm 3 ) were analyzed by high-resolution peripheral quantitative computed tomography of the hand joints of individuals at risk of RA. AMPA response was profiled, including reactivities against citrullinated proteins (vimentin, enolase, and fibrinogen) as well as carbamylated and acetylated vimentin. All subjects were followed up for the development of RA.Results. Subjects at risk of developing RA (n = 75) who had broad-spectrum AMPAs (6-8 reactivities) had significantly more severe microstructural changes, including a higher mean AE SD number of cortical microchannels per joint (95 AE 3) and lower total volumetric BMD (vBMD; 265 AE 45), trabecular vBMD (176 AE 42), and cortical vBMD (585 AE 138), than those with moderate AMPA reactivity (3-5 reactivities) (number of cortical microchannels, 79 AE 30; total vBMD, 293 AE 33; trabecular vBMD, 195 AE 32; and cortical vBMD, 627 AE 91) and those with narrow AMPA reactivity (1-2 reactivities) (number of cortical microchannels, 47 AE 20; total vBMD, 311 AE 34; trabecular vBMD, 211 AE 30; and cortical vBMD, 674 AE 56). Progressors to RA had significantly higher numbers of cortical microchannels (103 AE 30 versus 71 AE 35) and lower bone volume (258 AE 37 versus 295 AE 34) compared to nonprogressors. Furthermore, rate of progression to RA was high in subjects with broad AMPA reactivity (48%) versus those with medium AMPA reactivity (26%) or narrow AMPA reactivity (0%), as well as in those with a high number of cortical microchannels (44%) versus those with a low number of cortical microchannels (10%).Conclusion. Microstructural changes in individuals at risk of RA are associated with broad-spectrum autoimmunity and predict the onset of RA. These data support the concept of structural priming of joints by autoimmunity before the onset of the inflammatory phase of the disease.

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Autoimmunity in 2019

Selmi

2020

Clinic Rev Allerg Immunol

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The Specificity of Monoclonal Anti–Citrullinated Protein Antibodies: Comment on the Article by Steen et al

Cited by 3 publications

References 8 publications

Pathogenic effector functions of ACPA: Where do we stand?

Pathogenic effector functions of ACPA: Where do we stand?

Microstructural Bone Changes Are Associated With Broad‐Spectrum Autoimmunity and Predict the Onset of Rheumatoid Arthritis

Autoimmunity in 2019

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