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Diagnostic and prognostic potential of joint imaging in patients with anti-citrullinated protein antibodies
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The introduction of novel therapeutic strategies set new goals for the patients’ outcome, which aims to achieve remission. This goal requires early diagnosis of RA and prompt efficient pharmacotherapy. The introduction of anti-citrullinated protein antibodies (ACPA) two decades ago allowed an earlier RA diagnosis. However, there are indications that ACPA positivity is still associated with higher rates of radiographic damage. As the small joints in hands and feet commonly are the first involved sites of inflammation, the role of different imaging modalities were studied regarding their diagnostic and prognostic impact for assessment of arthritis in RA. Further, ultrasound (US) and radiography were used to study the association between RA-specific antibodies and the occurrence of arthritis and joint damage in systemic lupus erythematosus (SLE).

The use of US allows assessment of soft tissue like joint capsules, tendons and bursae. Used for a live scanning, it is easy to detect effusions and edema. Doppler indicates vasoproliferation were inflammation is present. Also, US seems to be more sensitive than radiography to detect minimal structural changes located at bone surfaces. We wanted to investigate whether US findings in a pre-RA stage can predict development of arthritis.

Digital X-ray radiogrammetry (DXR) is a technique based on computerized analyses of standard hand radiographs to calculate peripheral bone mineral density (BMD) of the three middle metacarpal bones (DXR-BMD). In order for early treatment decisions, we aimed to study whether changes in DXR-BMD loss after 3 months can predict radiographic damage in early RA.

In conclusion, the studies showed that ACPA-positivity is still associated with a higher risk of radiographic damage regardless of early treatment decisions. Therefore, close radiographic monitoring and readiness to intensive treatment is warranted in ACPA-positive patients. This thesis also shows that erosions detected by US in ACPA-positive patients with arthralgia predict development of clinical arthritis. Also, the magnitude of DXR-BMD loss helps identify patients at higher risk for future radiographic damage, and may therefore help to improve early treatment decisions. Finally, US and radiography confirm a higher rate of arthritis and erosions also in SLE patients who are positive for RA-specific antibodies.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. , p. 56
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1658
National Category
Rheumatology and Autoimmunity Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:liu:diva-153624DOI: 10.3384/diss.diva-153624ISBN: 9789176851456 (print)OAI: oai:DiVA.org:liu-153624DiVA, id: diva2:1275057
Public defence
2019-01-18, Belladonna, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2019-01-04 Created: 2019-01-04 Last updated: 2019-05-06Bibliographically approved
List of papers
1. Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus: results from two well-defined European cohorts.
Open this publication in new window or tab >>Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus: results from two well-defined European cohorts.
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2016 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 18, no 1Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data.

METHODS: Cases of SLE (n = 441) from Linköping, Sweden, and Leiden, the Netherlands, were classified according to American College of Rheumatology (ACR) and/or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. IgG anti-CCP, anti-CAP and anti-CarP were analysed by immunoassays. Radiographic data from 102 Swedish patients were available.

RESULTS: There were 16 Linköping (6.8%) and 11 Leiden patients (5.4%) who were anti-CCP-positive, of whom approximately one third were citrulline-dependent: 40/441 (9.1%) were anti-CarP-positive, and 33% of the anti-CarP-positive patients were identified as anti-CCP-positive. No associations were found comparing anti-CCP or anti-CarP with ACR-defined phenotypes, immunologic abnormalities or smoking habits. Radiographically confirmed erosions were found in 10 patients, and were significantly associated with anti-CCP, anti-CarP and RF. Musculoskeletal ultrasonography scores were higher in anti-CCP-positive compared to anti-CCP-negative patients.

CONCLUSIONS: In the hitherto largest anti-CarP study in SLE, we demonstrate that anti-CarP is more prevalent than anti-CCP and that the overlap is limited. We obtained some evidence that both autoantibodies seem to be associated with erosivity. Similar pathogenetic mechanisms to those seen in RA may be relevant in a subgroup of SLE cases with a phenotype dominated by arthritis.

Place, publisher, year, edition, pages
BioMed Central, 2016
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-133852 (URN)10.1186/s13075-016-1192-x (DOI)000390276600002 ()27912793 (PubMedID)
Note

Funding agencies: County Council of Ostergotland; Swedish Society for Medical Research; Swedish Rheumatism Association; Swedish Society of Medicine; Professor Nanna Svartz foundation; King Gustaf V 80-year foundation; Dutch Arthritis Foundation; IMI JU project, BeTheCure [

Available from: 2017-01-12 Created: 2017-01-12 Last updated: 2019-01-04
2. Decrease in bone mineral density during three months after diagnosis of early rheumatoid arthritis measured by digital X-ray radiogrammetry predicts radiographic joint damage after one year
Open this publication in new window or tab >>Decrease in bone mineral density during three months after diagnosis of early rheumatoid arthritis measured by digital X-ray radiogrammetry predicts radiographic joint damage after one year
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2017 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, article id 195Article in journal (Refereed) Published
Abstract [en]

Background: Periarticular osteopenia is an early sign of incipient joint injury in rheumatoid arthritis (RA), but cannot be accurately quantified using conventional radiography. Digital X-ray radiogrammetry (DXR) is a computerized technique to estimate bone mineral density (BMD) from hand radiographs. The aim of this study was to evaluate whether decrease in BMD of the hands (BMD loss), as determined by DXR 3 months after diagnosis, predicts radiographic joint damage after 1 and 2 years in patients with early RA. Methods: Patients (n = 176) with early RA (amp;lt; 12 months after onset of symptoms) from three different Swedish rheumatology centers were consecutively included in the study, and 167 of these patients were included in the analysis. Medication was given in accordance with Swedish guidelines, and the patients were followed for 2 years. Rheumatoid factor and antibodies to cyclic citrullinated peptides (anti-CCP) were measured at baseline, and 28-joint Disease Activity Score (DAS28) was assessed at each visit. Radiographs of the hands and feet were obtained at baseline, 3 months (hands only) and 1 and 2 years. Baseline and 1-year and 2-year radiographs were evaluated by the Larsen score. Radiographic progression was defined as a difference in Larsen score above the smallest detectable change. DXR-BMD was measured at baseline and after 3 months. BMD loss was defined as moderate when the decrease in BMD was between 0.25 and 2.5 mg/cm(2)/month and as severe when the decrease was greater than 2.5 mg/cm(2)/month. Multivariate regression was applied to test the association between DXR-BMD loss and radiographic damage, including adjustments for possible confounders. Results: DXR-BMD loss during the initial 3 months occurred in 59% of the patients (44% moderate, 15% severe): 32 patients (19%) had radiographic progression at 1 year and 45 (35%) at 2 years. In multiple regression analyses, the magnitude of DXR-BMD loss was significantly associated with increase in Larsen score between baseline and 1 year (p = 0.033, adjusted R-squared = 0.069). Conclusion: DXR-BMD loss during the initial 3 months independently predicted radiographic joint damage at 1 year in patients with early RA. Thus, DXR-BMD may be a useful tool to detect ongoing joint damage and thereby to improve individualization of therapy in early RA.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2017
Keywords
Digital X-ray radiogrammetry; Bone mineral density; Disease progression; Early rheumatoid arthritis
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-141121 (URN)10.1186/s13075-017-1403-0 (DOI)000409495000002 ()28865482 (PubMedID)
Note

Funding Agencies|Swedish Rheumatism Association; Norrbacka-Eugenia foundation; King Gustav V 80-year Foundation; Swedish Medical Society; ALF Grants from Region Ostergotland; Linkoping University Hospital Research Fund; Foundation for Assistance to Disabled People in Skane (Stiftelsen for Bistand at Rorelsehindrade i Skane)

Available from: 2017-09-27 Created: 2017-09-27 Last updated: 2019-01-04

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