ORCID Profile
0000-0001-9264-6463
Current Organisations
University of Birmingham
,
Queensland Health
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 02-2020
DOI: 10.1002/PSB.1825
Publisher: Springer Science and Business Media LLC
Date: 29-07-2023
DOI: 10.1186/S12014-023-09420-1
Abstract: Systemic lupus erythematosus (SLE) is a clinically and biologically heterogenous autoimmune disease. We aimed to investigate the plasma proteome of patients with active SLE to identify novel subgroups, or endotypes, of patients. Plasma was collected from patients with active SLE who were enrolled in the British Isles Lupus Assessment Group Biologics Registry (BILAG-BR). The plasma proteome was analysed using a data-independent acquisition method, Sequential Window Acquisition of All theoretical mass spectra mass spectrometry (SWATH-MS). Unsupervised, data-driven clustering algorithms were used to delineate groups of patients with a shared proteomic profile. In 223 patients, six clusters were identified based on quantification of 581 proteins. Between the clusters, there were significant differences in age (p = 0.012) and ethnicity (p = 0.003). There was increased musculoskeletal disease activity in cluster 1 (C1), 19/27 (70.4%) (p = 0.002) and renal activity in cluster 6 (C6) 15/24 (62.5%) (p = 0.051). Anti-SSa/Ro was the only autoantibody that significantly differed between clusters (p = 0.017). C1 was associated with p21-activated kinases (PAK) and Phospholipase C (PLC) signalling. Within C1 there were two sub-clusters (C1A and C1B) defined by 49 proteins related to cytoskeletal protein binding. C2 and C6 demonstrated opposite Rho family GTPase and Rho GDI signalling. Three proteins (MZB1, SND1 and AGL) identified in C6 increased the classification of active renal disease although this did not reach statistical significance (p = 0.0617). Unsupervised proteomic analysis identifies clusters of patients with active SLE, that are associated with clinical and serological features, which may facilitate biomarker discovery. The observed proteomic heterogeneity further supports the need for a personalised approach to treatment in SLE.
Publisher: BMJ
Date: 19-05-2021
DOI: 10.1136/ANNRHEUMDIS-2021-EULAR.2415
Abstract: We present the case of a 28 year old Black-British female with severe SLE requiring treatment with rituximab in 2012 due to persistent low-grade activity and severe episodes of pleuro-pericardial effusions, pancytopaenia, fever and weight loss Her other background includes beta-thalassaemia trait and excision of calcific fibrotic tissue on bilateral anterolateral orbits in 2015. In 2018 she reported an 18-month history of non-tender, non-fluctuant, slow growing left thigh mass with USS revealing a well demarcated subcutaneous complex cystic lesion of ~2x4x7cm. There was no preceding trauma or skin infection. Histology from a needle biopsy revealed diffuse histiocytosis with positive immunohistochemistry (ICH) for S100, CD68 and CD31, it was negative for CD1a, consistent with Extra-nodal Rosai-Dorfman disease (RDD ). She developed constitutional symptoms after reporting months of gradual weight loss with gradual ESR, CRP rise and leucocytosis. Her SLE symptoms were stable and given lack of SLE-specific symptoms PET-CT was used to identify systemic RDD the thigh mass showed strong FDG avidity along with a small focus of uptake in the small bowel, thought to be RDD related with no other areas of uptake. She had ongoing ooze from the enlarging thigh lesion (5 x 26 x 15 cm), this was sent for MCS and AAFB which isolated Mycobacterium avium . She was treated with rif icin, ethambutol and clarithromycin resulting in improved thigh lesion, constitutional symptoms and inflammatory markers. [1]To describe a rare associated complication of severe SLE and to educate and inform clinicians regarding possible masquerades of disease [2]To education and inform about the approach to diagnosis of mycobacterium infection. Case report and literature review. Mycobacterium infections rarely complicate RDD to date, only one case report is published involving an HIV infected patient with RDD confirmed on LN biopsy presenting with splenomegaly and treated with oral corticosteroids (OCS) complicated by Mycobacterium avium complex and Salmonella enterica confirmed on bone marrow biopsy/culture, similar to our patient, he presented with constitutional symptoms and weight loss (2) . Mycobacterium can also mimic RDD, a case report has described a 74 year old with tender lymphadenopathy diagnosed with RDD on LN biopsy. She was treated with IV and OCS, but was unresponsive. A repeat LN biopsy and CT imaging revealed the presence of mycobacterium kansasii her biopsy was positive for CD68/S100 throughout. Of note, she had high levels of anti-interferon autoantibodies and was diagnosed with adult-onset immunodeficiency syndrome (3) . This case illustrates the need for a MDT approach for multi-system diseases such as SLE and RDD, and the need to consider atypical infections when blood tests are incongruent with clinical state. [1]Bruce-Brand C, Schneider JW, Schubert P. Rosai-Dorfman disease: an overview. J Clin Pathol. 2020 Nov (11):697-705. doi: 10.1136/jclinpath-2020-206733. [2]Olmedo-Reneaum A, Molina-Jaimes A, Conde-Vazquez E, Montero-Vazquez S. Rosai-Dorfman disease and superinfection due to Salmonella enterica and Mycobacterium avium complex in a patient living with HIV. IDCases. 2020 Jan 14 :e00698. [3]King YA, Hu CH, Lee YJ, Lin CF, Liu D, Wang KH. Disseminated cutaneous Mycobacterium kansasii infection presenting with Rosai-Dorfman disease-like histological features in a patient carrying anti-interferon-γ autoantibodies. J Dermatol. 2017 Dec (12):1396-1400. Image 1. Table 1. SLE Clinical History Diagnosed 2006 (‘97 ACR Classification Criteria) Clinical -Polyarthritis -Glandular (lacrimal swelling) -Pericardial effusion/Pleural Effusion -Myositis Serological -Anti-nuclear antibody (ANA) -Anti-dsDNA -Anti-U1-RNP -Anti- SS-A/Ro -Lupus Anticoagulant Previous SLE Treatment -Hydroxychloroquine (HCQ) -Methotrexate (MTX) -Azathioprine (AZA) -Rituximab (RTX) None declared
Publisher: Wiley
Date: 12-2015
DOI: 10.1111/IMJ.12896
Abstract: While efficacy of combination treatment with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ) ('triple therapy') has been shown in clinical trials, few studies have examined its longevity in a real-life setting. Our aim was to assess the tolerability, longevity and efficacy of a triple disease-modifying anti-rheumatic drug (DMARD) regimen initiated in new-onset rheumatoid arthritis (RA) patients. Patients who met 1987 American College of Rheumatology criteria for RA with disease duration less than 2 years were offered triple therapy upon diagnosis. Treatment was intensified according to a response-driven step-up algorithm, which included progression to leflunomide (LEF) or a biologic agent. Of 181 new-onset RA patients, 119 commenced triple therapy. Median duration of triple therapy was 39 weeks, and 23.5% remained on it at last follow up, with median follow up 104 weeks. Continuous therapy with any three-DMARD combination (including LEF) occurred in 32% at last follow up, with median duration of 70 weeks. Cessation of at least one of MTX, SSZ or HCQ occurred because of an adverse event in 38%, remission in 7% and incomplete response in 28% of patients. SSZ accounted for 49% of initial drug withdrawals for an adverse event. Continuation of three-drug therapy did not significantly influence the proportion of patients achieving remission or low disease activity (LDA). Triple therapy in new-onset RA was reasonably well tolerated, persisting for median 39 weeks. SSZ intolerance commonly reduces longevity of triple therapy. Treating to the target of remission or LDA is more important than the number of DMARD continued.
Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism
Date: 06-2019
Publisher: MedCrave Group Kft.
Date: 19-04-2017
Publisher: Oxford University Press (OUP)
Date: 11-2016
DOI: 10.1093/OMCR/OMW083
Publisher: Wiley
Date: 17-05-2021
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Kevin Su.