33 research outputs found
Mycophenolate mofetil in the treatment of lupus nephritis
Lupus nephritis is a complication of systemic lupus erythematosus, which has significant morbidity and mortality. The accepted standard of treatment for severe lupus nephritis is cyclophosphamide for induction of remission. This has significant adverse effects including severe infection and amenorrhea. In addition, although cyclophosphamide induces remission, long-term mortality does not seem to be altered. Mycophenolate mofetil (MMF) is an immunosuppressive agent originally used in solid organ transplantation, which has been compared with cyclophosphamide in trials for lupus nephritis. Randomized trials with MMF have been relatively small, although pooled data seem to suggest that it is at least as effective as cyclophosphamide in inducing remission. In addition, MMF has also been associated with a reduced risk of infection and amenorrhea, although this finding is not universal. MMF appears to be associated with more diarrhea compared with cyclophosphamide. MMF is likely to be a useful treatment for lupus nephritis, although available trial data are limited due to the small size of previous studies. A large trial (the Aspreva Lupus Management Study) is currently underway to attempt to establish the place of MMF in treatment of lupus nephritis
Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus
Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients’ sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus
A role for gut-associated lymphoid tissue in shaping the human B cell repertoire
PMCID: PMC3754866Rockefeller University Press grants the public the non-exclusive right to copy, distribute, or display this Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at
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Improved monitoring of clinical response in Systemic Lupus Erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1
This work was funded by Arthritis Research UK. MJL holds an Arthritis Research UK Clinician Scientist Fellowship (19631), and was previously supported by the St Thomas’ Lupus Trust. The study received support from the National Institute for Health Research (NIHR)-funded Flow Cytometry Core Facility and the Biomedical Research Centre based at Guy’s & St. Thomas’ National Health Service (NHS) Foundation Trust, in partnership with King’s College London
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Physician-patient communication in rheumatology: a systematic review
The nature of physician–patient interaction can have a significant impact on patient outcomes through information-sharing and disease-specific education that can enhance patients’ active involvement in their care. The aim of this systematic review was to examine all the empirical evidence pertaining to aspects of physician–patient communication and its impact on patient outcomes. A systematic search of five electronic databases (MEDLINE, PsycINFO, EMBASE, CINAHL, and Web of Science) was undertaken from earliest record to December 2016. Studies were eligible if they: (1) included adult participants (18 years or over) with a diagnosis of a rheumatic condition; (2) were of quantitative, qualitative or mixed methods design; (4) were surveys, observational and interventional studies; (5) were published in the English language; and (6) reported findings on either various physician–patient communication aspects alone or in combination with physical and psychological outcomes. Searches identified 455 papers. Following full-text retrieval and assessment for eligibility and quality, ten studies were included in the review; six quantitative, one mixed methods, and three qualitative papers. Higher levels of trust in the physician and active patient participation in the medical consultation were linked to lower disease activity, better global health, less organ damage accrual, greater treatment satisfaction with fewer side effects from the medication, more positive beliefs about control over the disease, and about current and future health. Future research could focus on the design and implementation of interventions incorporating communications skills and patient-education training
Reversible Cerebral Vasoconstriction Syndrome and Raynaud’s Phenomenon: Is There a Link between the Pathogeneses of Their Underlying Complex Etiology? A Case Report and Literature Review
Reversible cerebral vasoconstriction syndrome (RCVS) typically manifests as a sudden, severe thunderclap headache due to narrowing of the cerebral arteries. Symptoms usually resolve within three months. An imbalance in cerebral vascular tone, an abnormal endothelial function, and a decreased autoregulation of cerebral blood flow are thought to be involved in the pathogenesis of RCVS. However, the precise origin of this condition is not yet fully understood. Symptoms of Raynaud’s phenomenon (RP) include vasospasm of arterioles of the digits. The pathophysiology of RP includes interactions between the endothelium, smooth muscle, and autonomic and sensory neurons that innervate arteries to help maintain vasomotor homeostasis. RP may occur before the clinical manifestation of a rheumatic condition. RCVS is rare in patients with autoimmune rheumatic disease. We describe a 54-year-old female who had a history of Raynaud’s phenomenon affecting her fingers and toes since the age of 12 years. The patient was diagnosed with RCVS in 2012. She described RCVS precipitants, including the regular use of cannabis, cocaine, and amphetamine and tobacco smoking. In 2021, she presented with oral ulcers, intermittent swallowing difficulties, and Raynaud’s phenomenon. Clinical examination revealed early sclerodactyly, and abnormal nail-fold capillaroscopy showed multiple giant capillaries, dilated capillary loops, and areas of capillary hemorrhage with capillary drop-out. The investigation revealed positive ANA, strongly positive SRP antibodies, and Ro60 antibodies. Our case report indicates that there may be a correlation between RCVS and Raynaud’s phenomenon, and a potential connection between RCVS and autoimmune rheumatic diseases. Hence, physicians must be aware of the red flags and subtle differences in neurological abnormalities, such as headaches, in patients with autoimmune rheumatic diseases who have an inactive clinical status to improve patient care and outcomes
Recent Advances in SLE Treatment Including Biologic Therapies
Systemic lupus erythematosus (SLE) is a long-term multisystem autoimmune rheumatic disease that can affect the skin, joints, kidneys, lungs, heart, and central nervous system. Clinical manifestations range from mild to severe and life-threatening diseases, which could be associated with poor outcomes, including morbidity, poor quality of life, and mortality. There is no cure for SLE, and the management is guided by organ system involvement, flare prevention, managing comorbidities, and reducing damage accumulation. Hydroxychloroquine is the most common drug that is used to control lupus disease activity. Anifrolumab is an antibody that inhibits all signaling through the type I interferon receptor and is licensed for the treatment of moderate to severe SLE. Voclosporin is a calcineurin inhibitor approved for the treatment of lupus nephritis. Belimumab as a biologic agent has been approved for the management of individuals with SLE and lupus nephritis. Despite the fact that rituximab has failed to meet its primary endpoints in clinical trials for SLE, rituximab can be used according to ACR and EULAR guidelines and is commonly used off-label for severe lupus flares. There is an unmet need for new biologic and novel therapeutic approaches in the management of SLE