scholarly journals Imaging of Joint and Soft Tissue Involvement in Systemic Lupus Erythematosus

2021 ◽  
Vol 23 (9) ◽  
Author(s):  
Andrea Di Matteo ◽  
Gianluca Smerilli ◽  
Edoardo Cipolletta ◽  
Fausto Salaffi ◽  
Rossella De Angelis ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Soft Tissue ◽  
Lupus Erythematosus ◽  
Structural Damage ◽  
Structural Changes ◽  
Soft Tissues ◽  
Imaging Techniques ◽  
Joint Involvement ◽  
Systemic Lupus ◽  
Muscle Involvement

Abstract Purpose of Review To highlight the potential uses and applications of imaging in the assessment of the most common and relevant musculoskeletal (MSK) manifestations in systemic lupus erythematosus (SLE). Recent Findings Ultrasound (US) and magnetic resonance imaging (MRI) are accurate and sensitive in the assessment of inflammation and structural damage at the joint and soft tissue structures in patients with SLE. The US is particularly helpful for the detection of joint and/or tendon inflammation in patients with arthralgia but without clinical synovitis, and for the early identification of bone erosions. MRI plays a key role in the early diagnosis of osteonecrosis and in the assessment of muscle involvement (i.e., myositis and myopathy). Conventional radiography (CR) remains the traditional gold standard for the evaluation of structural damage in patients with joint involvement, and for the study of bone pathology. The diagnostic value of CR is affected by the poor sensitivity in demonstrating early structural changes at joint and soft tissue level. Computed tomography allows a detailed evaluation of bone damage. However, the inability to distinguish different soft tissues and the need for ionizing radiation limit its use to selected clinical circumstances. Nuclear imaging techniques are valuable resources in patients with suspected bone infection (i.e., osteomyelitis), especially when MRI is contraindicated. Finally, dual energy X-ray absorptiometry represents the imaging mainstay for the assessment and monitoring of bone status in patients with or at-risk of osteoporosis. Summary Imaging provides relevant and valuable information in the assessment of MSK involvement in SLE.

scholarly journals AB0087 AUTOANTIBODIES DIRECTED AGAINST HOMOCYSTEINYLATED ALPHA 1 ANTITRYPSIN AS A POTENTIAL NEW BIOMARKER FOR ARTHRITIS IN PATIENTS AFFECTED BY SYSTEMIC LUPUS ERYTHEMATOSUS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1073.1-1073
Author(s):  
F. Natalucci ◽  
F. Ceccarelli ◽  
T. Colasanti ◽  
G. Olivieri ◽  
A. I. Celia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Imaging Techniques ◽  
Laboratory Data ◽  
Joint Involvement ◽  
Sample Collection ◽  
Systemic Lupus ◽  
Alpha 1 Antitrypsin

Background:Joint involvement represents one of the most frequent features in patients affected by Systemic Lupus Erythematosus (SLE). This manifestation is characterized by a great heterogeneity in phenotype and severity: the application of more sensitive imaging techniques identified an erosive damage in about 25% of patients (1). This damage has been associated with autoantibodies, such as anti-citrullinated (ACPA) and anti-carbamylated proteins (antiCarP), previously identified in patients Rheumatoid Arthritis (RA) patients. Recently, homocysteinylated alpha 1 antitrypsin (Hcy-1A1AT) has been identified as a new antigenic target of autoantibodies in seronegative RA patients: in detail, anti-homocysteinylated alpha 1 antitrypsin (anti – HATA) antibodies have been identified in 75.7% of patients (2).Objectives:In the present study, we aimed at determining the prevalence of anti – HATA in a cohort of SLE patients.Methods:We evaluated patients affected by SLE according to the 1997 ACR criteria. Demographic, clinical, and laboratory data were collected in a standardized computerized electronically filled form. Each subject underwent peripheral blood sample collection. Hcy-A1AT was obtained by in vitro modification of native A1AT and used as antigens by ELISA to test the presence of anti–HATA in sera obtained from enrolled subjects. Finally, we investigated the presence of ACPA and Rheumatoid Factor (RF) commercial ELISA kits and of anti-CarP (home-made ELISA) by a home-made ELISA in SLE patients’ sera. As control, we enrolled 40 patients affected by Osteoarthritis (OA) and 41 healthy subjects (HS).Results:The present analysis included 88 SLE patients (M/F 6/82 median age 47 years (IQR 17), median disease duration 156 months (IQR 180). Joint involvement was observed in 75 SLE patients (85.2%): in detail, 65 patients referred arthritis and the remaining 10 inflammatory arthralgias. We identified the presence of anti–HATA IgG in 38 SLE patients (43.2%). This prevalence was significantly higher in comparison with OA and HS subjects [15.0% (p<0.001) and 0% (p<0.0001), respectively; Figure 1A]. Focusing on the SLE cohort, no differences were observed between patients with and without joint involvement in anti–HATA IgG prevalence (41.3% versus 34.7%, respectively; p=0.34). However considering SLE patients according to the presence of arthralgia and arthritis, the prevalence of anti-HATA was significantly higher in patients with arthritis in comparison with those patients with arthralgias (46.1% versus 11.1%, p=0.02; figure 1B). Finally, no significant association between anti-HATA and the other tested autoantibodies (RF, ACPA, anti-CarP) was found.Conclusion:We evaluated the prevalence of anti-HATA in a cohort of SLE patients. The prevalence of these autoantibodies was significantly higher in SLE patients than in OA patients and in HS. The association with arthritis suggests a possible role for anti-HATA as biomarkers of SLE-related joint involvement.References:[1]Ceccarelli F. Perricone C. Cipriano E. et al. Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment. Seminar in Arthritis and Rheumatism, 47(1), 53 – 64.[2]Colasanti T. Sabatinelli D. Mancone et al. Homocysteinylated alpha 1 antitrypsin as an antigenic target of autoantibodies in seronegative rheumatoid arthritis patients. Journal of Autoimmunity 2020 Sep;113:102470.Disclosure of Interests:None declared

Erosive arthritis in systemic lupus erythematosus: not only Rhupus

Lupus ◽  
2021 ◽  
pp. 096120332110516
Author(s):  
Fulvia Ceccarelli ◽  
Francesco Natalucci ◽  
Giulio Olivieri ◽  
Carlo Perricone ◽  
Carmelo Pirone ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Imaging Techniques ◽  
Power Doppler ◽  
Inflammatory Factors ◽  
Joint Involvement ◽  
Systemic Lupus ◽  
Biological Drugs ◽  
Erosive Arthritis ◽  
Therapeutic Decisions

Systemic lupus erythematosus (SLE)–related arthritis has been traditionally defined as non-erosive and is therefore considered a minor manifestation requiring a mild treatment. However, the concept of non-erosive arthritis in SLE has been challenged with the advent of sensitive imaging techniques, such as high-resolution ultrasound with power Doppler or magnetic resonance. The application of these new imaging tools has demonstrated that up to 40% of SLE patients with joint involvement can develop erosive damage. Thus, this more aggressive phenotype can be identified not only in patients overlapping with rheumatoid arthritis (RA). This issue has been considered for the first time in the classification criteria proposed by Systemic Lupus International Collaborating Clinics in 2012, in which the old definition of “non-erosive arthritis” was replaced with either synovitis or tenderness in two or more joints with morning stiffness, suggesting the possible presence of an erosive phenotype. Accordingly, the 2019 EULAR/ACR’s SLE recommendations advise treatment with immunosuppressant or biological drugs for patients with RA-like moderate arthritis. As a result, several studies have investigated the presence of biomarkers associated with SLE erosive damage. A relevant role seems to be played by the autoantibodies directed against post-translational modified proteins: above all, a significant association has been observed with antibodies directed against citrullinated and carbamylated proteins. Conversely, the rheumatoid factor was not associated with this more aggressive SLE-related arthritis. Nonetheless, some pro-inflammatory factors have been associated with erosive damage in SLE patients. These results suggest new pathogenic mechanisms underlining erosive arthritis, only partially shared with RA. Hence, in the present narrative review, we summarized available data about erosive arthritis in SLE patients, in the light of its impact on therapeutic decisions.

FRI0159 EROSIVE ARTHRITIS IN SYSTEMIC LUPUS ERYTHEMATOSUS: APPLICATION OF CLUSTER ANALYSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 663-664
Author(s):  
F. Ceccarelli ◽  
F. Natalucci ◽  
C. Perricone ◽  
E. Cipriano ◽  
C. Pirone ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cluster Analysis ◽  
Lupus Erythematosus ◽  
Imaging Techniques ◽  
Univariate Analysis ◽  
Laboratory Data ◽  
Joint Involvement ◽  
Systemic Lupus ◽  
Research Support ◽  
Erosive Arthritis

Background:Systemic Lupus Erythematosus (SLE) related arthritis has been traditionally defined non-erosive and then considered a minor manifestation. Thanks to the application of more sensitive imaging techniques, such as ultrasonography (US), erosive damage has been identified in up to 40% of SLE patients with joint involvement, suggesting the need for more appropriate treatment (1). Antibodies directed against citrullinated and carbamilated proteins (ACPA and anti-CarP, respectively) have been associated with erosive damage and then proposed as biomarkers for this more aggressive phenotype (2).Objectives:Here, we evaluated a large SLE cohort with joint involvement by using cluster analysis, in order to identify the disease phenotype associated with erosive arthritis.Methods:For this analysis, we enrolled consecutive SLE patients (ACR 1997 criteria) with a clinical history of joint involvement (arthritis/arthralgia). Clinical and laboratory data were collected in a standardized computerized electronically filled form, including demographics, past medical history with the date of diagnosis, co-morbidities, previous and concomitant treatments, serological status. The presence of rheumatoid factor (RF), ACPA and anti-CarP was investigated by ELISA test. Erosive damage was assessed by ultrasonography at level of metacarpophalangeal, proximal interphalangeal and metatarsophalangeal joints (MyLab Eight Exp, Esaote, Florence, Italy). Data have been analysed by hierarchic cluster analysis (SPSS program, IBM).Results:We enrolled 203 patients [M/F 12/191, median age 46.0 years (IQR 18); median disease duration 120.0 months (IQR 108)]. Erosive damage was identified in 53 patients (26.1%), all of them referring at least one episode of arthritis during disease course. Moving on autoantibodies status, RF was positive in 29.5%, anti-CarP in 28.5% and ACPA in 11.2%. The univariate analysis demonstrated a significant association between US-detected erosive damage and anti-CarP (p=0.01), ACPA (p=0.03), and renal manifestations (p=0.03). In Figure 1 we reported the dendrogram obtained from cluster analysis, allowing the identification of four cluster. Positivity for ACPA, anti-CarP, erosive damage, Jaccoud’s arthropathy and renal manifestations were allocated in the same cluster. Interestingly, RF resulted allocated in a different cluster, including ENA, anti-SSA and anti-SSB antibodies.Conclusion:The application of cluster analysis allowed the identification of a specific SLE phenotype, characterized by erosive damage, renal manifestations and positivity for anti-CarP and ACPA. We could speculate about the presence of a shared pathogenic mechanism, involving NETosis, contributing to nephritis and erosive arthritis.References:[1]Ceccarelli F et al. Semin Arthritis Rheum 2017[2]Ceccarelli F et al. Arthritis Res Ther 2018Disclosure of Interests:Fulvia Ceccarelli: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, enrica cipriano: None declared, Carmelo Pirone: None declared, Giulio Olivieri: None declared, Tania Colasanti: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

Risk of osteonecrosis in systemic lupus erythematosus: An 11-year Chinese single-center cohort study

Lupus ◽  
2021 ◽  
pp. 096120332110211
Author(s):  
Yin Long ◽  
Shangzhu Zhang ◽  
Jiuliang Zhao ◽  
Hanxiao You ◽  
Li Zhang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Risk Factor ◽  
Femoral Head ◽  
Lupus Erythematosus ◽  
Femoral Head Necrosis ◽  
Joint Involvement ◽  
Multiple Site ◽  
Systemic Lupus ◽  
Cns Involvement

Objective Osteonecrosis (ON), which can lead to physical disability, is a common complication of systemic lupus erythematosus (SLE). The purpose of this study was to determine the prevalence of ON and identify possible risk factors in Chinese SLE patients. Methods SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were recruited from the Peking Union Medical College Hospital. The chi-square test (χ 2 test) and multivariate regression analyses were used to evaluate risk factors. The Cox proportional-hazards model was used to construct the survival curves and estimate the simultaneous effects of prognostic factors on survival. Results We consecutively enrolled 1,158 patients, of which 88 patients (7.6%) developed ON. Among ON patients, 57.1% of patients had isolated femoral head necrosis and 42.9% had multiple joint involvement. The mean age of ON patients (24.62 ± 8.89 years) was significantly younger than SLE patients without ON (27.23 ± 10.16 years, p = 0.09). The ON group presented with a much longer disease course (10.68 ± 5.97 years, p < 0.001) and increased incidence of arthritis, kidney, and central nervous system (CNS) involvement (65.9% [ p < 0.05], 57.6% [ p < 0.05], and 16.5% [ p < 0.05], respectively, in the ON group). ON patients were more likely to be treated with glucocorticoid (GC) and to receive a high dose of prednisolone at the initial stage of SLE ( p < 0.05). The percentage of patients who received hydroxychloroquine was much higher in the control group ( p < 0.001). Cox regression analysis suggested that CNS involvement and GC therapy were two independent risk factors for ON in SLE patients. The presence of anti-phospholipid antibodies (aPLs) was a risk factor for multiple joint necrosis (odds ratio: 6.28, p = 0.009). Conclusions ON remains a serious and irreversible complication in SLE. In addition to glucocorticoid therapy, we found that CNS system involvement was a risk factor for ON, while the administration of hydroxychloroquine was a protective factor. The clinical characteristics of multiple site ON patients were distinct from isolated femoral head necrosis patients. The presence of aPLs was a risk factor for multiple site osteonecrosis.

scholarly journals POS0685 MYCOPHENOLATE MOFETIL IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: FIVE-YEARS DRUG SURVIVAL IN RENAL AND NON-RENAL INVOLVEMENT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 588.2-588
Author(s):  
G. Olivieri ◽  
F. Ceccarelli ◽  
F. Natalucci ◽  
F. R. Spinelli ◽  
C. Alessandri ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mycophenolate Mofetil ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Treatment Duration ◽  
Retention Rate ◽  
Renal Involvement ◽  
Joint Involvement ◽  
Systemic Lupus ◽  
Median Treatment

Background:The updated EULAR recommendations for the management of systemic lupus erythematosus (SLE) underline the use of Mycophenolate Mofetil (MMF) in the treatment of different disease related manifestations (1). Several randomized controlled trials have demonstrated the efficacy of MMF in lupus nephritis (LN) patients but only case series and open-labelled trials have analyzed the use of this drug in other than LN features. Moreover, no data are available about the MMF retention rate in a real-life setting.Objectives:The present study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a large monocentric SLE cohort. Secondly, we investigated the influence of MMF in disease activity changes and chronic damage progression.Methods:We performed a longitudinal study including all the SLE patients (ACR 1997 criteria) starting MMF treatment in our Lupus Clinic. Data about indications, mean dosage, duration of treatment and reasons for drug withdrawal were registered. The DRR was estimated using the Kaplan–Meier method. Disease activity and chronic damage were assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SLICC Damage Index (SDI), respectively.Results:The present analysis included 162 SLE patients (M/F 22/140, median age at the disease diagnosis 25.5 years, IQR 13). At the beginning of MMF treatment, we registered a median age of 34 months (IQR 21) and a median disease duration of 72 months (IQR 123). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%), followed by neuropsychiatric involvement (10, 6.2%), and others disease related manifestations (12, 7.4%; in particular skin involvement, hematological features, myositis, vasculitis). MMF was administered at a mean daily dosage of 2.1±0.6 grams; no differences in dosage were found between the different indications (p=ns).At the longitudinal analysis, we registered a median treatment duration of 30 months (IQR 55). Figure 1 reported data about DRR: in particular, at 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (NLN) (60.5%; p=ns). Interestingly, the DRR at 60 months was higher in the subgroup of patients treated for joint involvement (75.4%), even without reaching a statistically significant difference. During the observation period, 92 patients (59.2%) discontinued MMF (median treatment duration at discontinuation 25 months, IQR 35). Interestingly, the main cause of withdrawal was the achievement of persistent remission, observed in 20 patients (21.7%), followed by loss of efficacy (19 patients, 20.5%), drug intolerance and pregnancy planning (17 patients for both reasons, 18,4%). Furthermore, our analysis confirmed MMF efficacy, as demonstrated by the significant reduction in SLEDAI-2k values after 4, 12 and 24 months of treatment (p< 0.0001 for all the time-points in comparison with baseline). In addition, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in SDI values (baseline: 0.6, IQR 1; last observation: 0.93, IQR 1; p=ns).Conclusion:The evaluation of a large SLE cohort demonstrated a good retention rate for MMF. In particular, our results demonstrated that MMF is also a safe and effective drug for SLE manifestation other than LN, in particular for joint involvement. Moreover, it is able to control disease activity and to prevent the progression of chronic damage.References:[1]Fanouriakis A et al. Ann Rheum Dis. 2019 Jun;78(6):736-745.Disclosure of Interests:None declared

Symptomatic osteonecrosis of the hip and knee in patients with systemic lupus erythematosus: Prevalence, pattern, and comparison of natural course

Lupus ◽  
2021 ◽  
pp. 096120332110310
Author(s):  
Mehmet Ersin ◽  
Mehmet Demirel ◽  
Mehmet Ekinci ◽  
Lezgin Mert ◽  
Çiğdem Çetin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Bone Structure ◽  
Survival Rates ◽  
Knee Joints ◽  
Joint Involvement ◽  
Systemic Lupus ◽  
Kaplan Meier ◽  
The Mean

Objective Osteonecrosis (ON), also known as avascular necrosis, is characterized by the collapse of the architectural bone structure secondary to the death of the bone marrow and trabecular bone. Osteonecrosis may accompany many conditions, especially rheumatic diseases. Among rheumatic diseases, osteonecrosis is most commonly associated with systemic lupus erythematosus (SLE). We assessed prevalence and distribution pattern of symptomatic ON in patients with SLE and compare the natural courses of hip and knee ON. Methods 912 SLE patients admitted between 1981 and 2012 were reviewed. SLE patients with symptomatic ON were retrospectively identified both from the existing SLE/APS database. The prevalence of symptomatic ON was calculated; with ON, the joint involvement pattern was determined by examining the distribution of the joints involved, and then the data about the hip and knee joints were entered in the Kaplan-Meier analysis. Kaplan-Meier methods were used to calculate 5- and 10-year rates of ON-related hip (the hip group) and knee survival (the knee group). Results Symptomatic ON developed in various joints in 97 of 912 patients with SLE, and the overall prevalence of ON was detected as 10.6%. The mean age at the time of SLE and ON diagnoses were 27.9 ± 9.9 (14–53) and 34.2 ± 11.3 (16–62) years, respectively. The mean duration from diagnosis of SLE to the first development of ON was 70.7± 60.2 (range = 0–216) months. The most common site for symptomatic ON was the hips (68%, n=66), followed by the knees (38%, n = 37). According to Kaplan-Meier analysis, hip and knee joint survival rates associated with 5-year ON were 51% and 88%, and 10-year survival rates were 43% and 84%, respectively. Conclusion We observed that the prevalence of symptomatic ON in patients with SLE was 10.6%. With the estimated 10-year survival rates of 40% versus 84% for the hip and knee joints, respectively, hip involvement may demonstrate a more aggressive course to end-stage osteoarthritis than the knee involvement.

European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance

2021 ◽  
pp. annrheumdis-2020-219373
Author(s):  
Martin Aringer ◽  
Ralph Brinks ◽  
Thomas Dörner ◽  
David Daikh ◽  
Marta Mosca ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Metabolic Diseases ◽  
Classification Criteria ◽  
Joint Involvement ◽  
Systemic Lupus ◽  
Entry Criterion ◽  
American College Of Rheumatology ◽  
European League Against Rheumatism ◽  
European League

Background/objectivesThe European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria.MethodsWe combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE.ResultsPositive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement.ConclusionsChanging the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.

MO430MASS-SPECTROMETRIC IDENTIFICATION OF POST-TRANSLATIONAL GUANIDINYLATED PROTEINS IN THE CONTEXT OF SYSTEMIC LUPUS ERYTHEMATOSUS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Juliane Hermann ◽  
Ute Raffetseder ◽  
Michaela Lellig ◽  
Joachim Jankowski ◽  
Vera Jankowski
Keyword(s):  
Mass Spectrometry ◽  
Systemic Lupus Erythematosus ◽  
High Resolution ◽  
Lupus Erythematosus ◽  
Imaging Techniques ◽  
Mass Spectrometric ◽  
Mass Spectrometric Imaging ◽  
Systemic Lupus ◽  
Notch 3 ◽  
Resolution Mass

Abstract Background and Aims With continuous identification of post-translational modified isoforms of proteins, it is becoming increasingly clear that post-translational modifications limit or modify the biological functions of native proteins are majorly involved in development of various chronic disease. This is mostly due to technically advanced molecular identification and quantification methods, mainly based on mass spectrometry. Mass spectrometry has become one of the most powerful tools for the identification of lipids. Method In this study, we used sophisticated high-resolution mass-spectrometric methods to analyze the soluble ligand of receptor Notch-3, namely the Y-box protein (YB)-1, in serum from systemic lupus erythematosus (SLE) patients. In addition, kidneys of lupus-prone (MRL.lpr) mice were analyzed by mass-spectrometric imaging techniques to identify the underlying pathomechanisms. Serum YB-1 was isolated by chromatographic methods, afterwards digested by trypsin and analyzed by matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). The kidneys were fixed in paraffin, then kidney sections were deparaffinized, tryptic digested and analyzed by mass-spectrometric imaging techniques. Mass-spectrometry of extracellular YB-1 in SLE patient serum revealed post-translational guanidinylation of two lysine’s within the highly conserved cold shock domain (CSD) of the YB-1 protein (YB-1-2G). Patients with increased disease activity and those with active renal involvement (lupus nephritis, LN) had a higher degree of dual-guanidinylation within the CSD. Of note, at least one of these modifications was present in all analyzed LN patients, whereas single-guanidinylated YB-1 was present in only one and double modification in none of the control individuals. Mass-spectrometric imaging analyses specifically localized YB-1-2G and increases Notch-3 expression in kidney sections from MRL.lpr mice. Results The data from this study clearly demonstrate the high potential of high-resolution mass spectrometric methods as well as mass spectrometric imaging techniques to identify pathomechanisms of diseases like SLE/LN.

AB0567 Joint Involvement in Patients Affected by Systemic Lupus Erythematosus: Application of The Swollen to Tender Joint Count Ratio

2015 ◽  
Vol 74 (Suppl 2) ◽  
pp. 1089.3-1089
Author(s):  
E. Cipriano ◽  
F. Ceccarelli ◽  
L. Massaro ◽  
F.R. Spinelli ◽  
F. Miranda ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Joint Involvement ◽  
Tender Joint Count ◽  
Systemic Lupus ◽  
Tender Joint ◽  
Count Ratio

scholarly journals Conformational changes in myeloperoxidase induced by ubiquitin and NETs containing free ISG15 from systemic lupus erythematosus patients promote a pro-inflammatory cytokine response in CD4+ T cells

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniel Alberto Carrillo-Vázquez ◽  
Eduardo Jardón-Valadez ◽  
Jiram Torres-Ruiz ◽  
Guillermo Juárez-Vega ◽  
José Luis Maravillas-Montero ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Molecular Dynamics ◽  
Conformational Changes ◽  
Lupus Erythematosus ◽  
Structural Changes ◽  
Hydration Status ◽  
Healthy Controls ◽  
Heme Group ◽  
Systemic Lupus ◽  
The Impact

Abstract Background Neutrophil extracellular traps (NETs) from patients with systemic lupus erythematosus (SLE) are characterized by lower ubiquitylation and myeloperoxidase (MPO) as a substrate. The structural and functional effect of such modification and if there are additional post-translational modifications (PTMs) are unknown. Methods To assess the expression and functional role of PTMs in NETs of patients with SLE; reactivation, proliferation and cytokine production was evaluated by flow cytometry using co-cultures with dendritic cells (DC) and CD4+ from SLE patients and healthy controls. The impact of ubiquitylation on MPO was assessed by molecular dynamics. The expression of ISG15 in NETs was evaluated by immunofluorescence and Western Blot. Results Fifteen patients with SLE and ten healthy controls were included. In the co-cultures of CD4+ lymphocytes with DC stimulated with ubiquitylated MPO or recombinant MPO, a higher expression of IFNγ and IL-17A was found in CD4+ from SLE patients (p < 0.05). Furthermore, with DC stimulated with ubiquitylated MPO a trend towards increased expression of CD25 and Ki67 was found in lupus CD4+ lymphocytes, while the opposite was documented in controls (p < 0.05). Through molecular dynamics we found the K129-K488-K505 residues of MPO as susceptible to ubiquitylation. Ubiquitylation affects the hydration status of the HEME group depending on the residue to which it is conjugated. R239 was found near by the HEME group when the ubiquitin was in K488-K505. In addition, we found greater expression of ISG15 in the SLE NETs vs controls (p < 0.05), colocalization with H2B (r = 0.81) only in SLE samples and increased production of IFNγ in PBMCs stimulated with lupus NETs compared to healthy controls NETs. Conclusion The ubiquitylated MPO has a differential effect on the induction of reactivation of CD4+ lymphocytes in patients with SLE, which may be related to structural changes by ubiquitylation at the catalytic site of MPO. Besides a lower ubiquitylation pattern, NETs of patients with SLE are characterized by the expression of ISG15, and the induction of IFNγ by Th1 cells.

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