Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment

Ceccarelli, Fulvia; Perricone, Carlo; Cipriano, Enrica; Massaro, Laura; Natalucci, Francesco; Capalbo, Giuseppe; Leccese, I.; Bogdanos, Dimitrios P.; Spinelli, Francesca Romana; Alessandri, Cristiano; Valesini, Guido; Conti, Fabrizio

doi:10.1016/j.semarthrit.2017.03.022

Cited by 63 publications

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“…Despite the relatively high frequency of joint involvement in patients with SLE, the pathogenetic picture remains incomplete and specific biomarkers are lacking [ 1 ]. Several studies suggest that a predisposing genetic background is detrimental in the development of joint involvement [ 29 – 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Joint involvement is one of the most common manifestations in patients with systemic lupus erythematosus (SLE), with a prevalence ranging from 69 to 95%. This feature significantly influences the patients’ quality of life, possibly leading to disability and impaired functional performance in daily activities [ 1 ]. SLE articular involvement could range from arthralgia to severe arthropathy, with inflammation and deformities [ 1 – 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Novel insights suggest that erosive damage, as assessed by musculoskeletal ultrasonography (US), occurs in up to 47% of patients with SLE [ 1 , 4 – 8 ]. It is likely that such an erosive phenotype of SLE arthritis may underlie specific pathogenic mechanisms [ 1 ]. Moreover, identification of prognostic biomarkers, able to identify patients at risk of developing this more aggressive phenotype, is mandatory.…”

Section: Introductionmentioning

confidence: 99%

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Anti-carbamylated protein antibodies as a new biomarker of erosive joint damage in systemic lupus erythematosus

et al. 2018

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BackgroundThe application of more sensitive imaging techniques, such as ultrasonography (US), changed the concept of non-erosive arthritis in systemic lupus erythematosus (SLE), underlining the need for biomarkers to identify patients developing the erosive phenotype. Anti-citrullinated peptide antibodies (ACPA), associated with erosions in inflammatory arthritis, have been identified in about 50% of patients with SLE with erosive arthritis. More recently, anti-carbamylated proteins antibodies (anti-CarP) have been associated with erosive damage in rheumatoid arthritis. We aimed to assess the association between anti-CarP and erosive damage in a large SLE cohort with joint involvement.MethodsWe evaluated 152 patients (male/female patients 11/141; median age 46 years, IQR 16; median disease duration 108 months, IQR 168). All patients underwent blood draw to detect rheumatoid factor (RF) and ACPA (commercial enzyme-linked immunosorbent assay (ELISA) kit), and anti-CarP (“home-made” ELISA, cutoff 340 aU/mL). The bone surfaces of the metacarpophalangeal and proximal interphalangeal joints were assessed by US: the presence of erosions was registered as a dichotomous value (0/1), obtaining a total score (0–20).ResultsThe prevalence of anti-CarP was 28.3%, similar to RF (27.6%) and significantly higher than ACPA (11.2%, p = 0.003). Erosive arthritis was identified in 25.6% of patients: this phenotype was significantly associated with anti-CarP (p = 0.004). Significant correlation between anti-CarP titer and US erosive score was observed (r = 0.2, p = 0.01).ConclusionsSignificant association was identified between anti-CarP and erosive damage in SLE-related arthritis, in terms of frequency and severity, suggesting that these antibodies can represent a biomarker of severity in patients with SLE with joint involvement.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-carbamylated protein antibodies as a new biomarker of erosive joint damage in systemic lupus erythematosus

et al. 2018

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“…The locomotor system symptoms are observed in systemic lupus erythematosus (SLE) and generally associated with transient, nonerosive, or erosive polyarthritis of proximal interphalangeal, metacarpophalangeal joints, and wrists. [ 1 2 ] In 1%–3% cases, the joint involvement pattern may be symmetric erosive polyarthritis as in rheumatoid arthritis (RA). The coexistence of SLE and RA called as rhupus syndrome.…”

Section: Introductionmentioning

confidence: 99%

Rhupus syndrome and Chiari's network

Sargın

Şentürk

Çildağ

2018

J Family Med Prim Care

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A 69-year-old female patient was admitted to our clinic with photosensitivity, symmetric erosive polyarthritis, and cutaneous vasculitis of lower extremities. Rhupus syndrome was diagnosed, and Chiari's network in the right atrium and interatrial septum patent foramen ovale was achieved on transthoracic and transesophageal echocardiography. If it is thought that increased prevalence of antiphospholipid antibodies in patients with rhupus, this congenital remnant is important for the thrombosis risk, cardiac event, and stroke. The association of both diseases may lead to more serious events and cause worse prognosis. Here, our aim is to present a 69-year-old female patient with rhupus syndrome presenting with cutaneous vasculitis and Chiari's network in the right atrium.

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“…General vague symptoms, like fatigue, are common. Otherwise, the most frequent manifestations are skin and joint involvement, which are present in a majority (>80%) of SLE patients, at least at some occasion during the disease course [4].…”

Section: Sle Classificationmentioning

confidence: 99%

Biomarkers of disease activity and organ damage in systemic lupus erythematosus

Wirestam¹

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Jag tror att när vi går igenom tiden att allt det bästa inte hänt än Håkan Hellström ABSTRACTSystemic lupus erythematosus (SLE) is a systemic inflammatory disease. Clinically, the distinction between ongoing inflammation attributed to SLE, and organ damage due to medication or co-morbidities remains challenging. In addition, SLE is a heterogeneous disease where the various disease phenotypes complicate the search for biomarkers that adequately reflect disease activity and/or signs of increasing organ damage. The aim of the thesis was to investigate and evaluate potential new biomarkers of disease activity and/or organ damage in SLE patients.High mobility group box protein-1 (HMGB1) is a nuclear non-histone protein that can shuttle to the cytoplasm, become secreted extracellularly, and participate in systemic inflammation.Administration of monoclonal anti-HMGB1 antibodies has been reported both to attenuate and intensify disease in animal models of arthritis and lupus. In Paper I of the thesis, circulating anti-HMGB1 was found in 23% of the SLE patients and correlated with disease activity variables. The biological role of these autoantibodies remains to be elucidated.As a consequence of massive circulating levels of cellular debris and immune complexes, SLE patients have insufficient capacity to remove such material via the reticuloendothelial system. Pentraxin 3 (PTX3) may possibly protect against lupus flares due to classical complement activation, opsonization of apoptotic cells, and cytokine induction. In Paper II, circulating PTX3 was found to be inhibited or exhausted by interferon (IFN)-α, a key cytokine of SLE pathogenesis, and serum levels of PTX3 in SLE patients were inversely related to IFN-α levels.Suppressed PTX3 levels may contribute to a vicious circle resulting in impaired waste clearance, autoantigen exposure and autoantibody production, and sustained disease activity.Osteopontin (OPN), a protein known to influence cell signaling and apoptosis, has been proposed as a marker of organ damage in pediatric lupus. In a Swedish cross-sectional study, circulating OPN levels were found to be raised in SLE (Paper III). In patients with recent-onset disease, OPN reflected disease activity, while in established disease, OPN appeared to mirror damage accrual and cardiovascular damage. In Paper IV, OPN was instead analyzed in an international longitudinal multi-center study based on patients with recent-onset SLE and follow-up data. OPN turned out to be a poor predictor of organ damage, but significant associations were observed between OPN and disease activity both at disease onset, as well as over 5 years of follow-up.In conclusion, increased anti-HMGB1 antibody and decreased PTX3 levels could potentially sustain the impaired waste-disposal. Of the molecules analyzed in this thesis, OPN seems to be the best marker of disease activity. Further studies of these proteins may help to better understand SLE pathogenesis and to optimize treatment of patients.

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Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment

Cited by 63 publications

References 100 publications

Anti-carbamylated protein antibodies as a new biomarker of erosive joint damage in systemic lupus erythematosus

Anti-carbamylated protein antibodies as a new biomarker of erosive joint damage in systemic lupus erythematosus

Rhupus syndrome and Chiari's network

Biomarkers of disease activity and organ damage in systemic lupus erythematosus

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