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Article ; Online: Mesenchymal Stem Cells in the Pathogenesis and Therapy of Autoimmune and Autoinflammatory Diseases.

Zaripova, Lina N / Midgley, Angela / Christmas, Stephen E / Beresford, Michael W / Pain, Clare / Baildam, Eileen M / Oldershaw, Rachel A

International journal of molecular sciences

2023 Volume 24, Issue 22

Abstract: Mesenchymal stem cells (MSCs) modulate immune responses and maintain self-tolerance. Their trophic activities and regenerative properties make them potential immunosuppressants for treating autoimmune and autoinflammatory diseases. MSCs are drawn to ... ...

Abstract	Mesenchymal stem cells (MSCs) modulate immune responses and maintain self-tolerance. Their trophic activities and regenerative properties make them potential immunosuppressants for treating autoimmune and autoinflammatory diseases. MSCs are drawn to sites of injury and inflammation where they can both reduce inflammation and contribute to tissue regeneration. An increased understanding of the role of MSCs in the development and progression of autoimmune disorders has revealed that MSCs are passive targets in the inflammatory process, becoming impaired by it and exhibiting loss of immunomodulatory activity. MSCs have been considered as potential novel cell therapies for severe autoimmune and autoinflammatory diseases, which at present have only disease modifying rather than curative treatment options. MSCs are emerging as potential therapies for severe autoimmune and autoinflammatory diseases. Clinical application of MSCs in rare cases of severe disease in which other existing treatment modalities have failed, have demonstrated potential use in treating multiple diseases, including rheumatoid arthritis, systemic lupus erythematosus, myocardial infarction, liver cirrhosis, spinal cord injury, multiple sclerosis, and COVID-19 pneumonia. This review explores the biological mechanisms behind the role of MSCs in autoimmune and autoinflammatory diseases. It also covers their immunomodulatory capabilities, potential therapeutic applications, and the challenges and risks associated with MSC therapy.
MeSH term(s)	Humans ; Mesenchymal Stem Cells/pathology ; Autoimmune Diseases/etiology ; Autoimmune Diseases/therapy ; Inflammation/therapy ; Inflammation/pathology ; Immune Tolerance ; Immunomodulation ; Hereditary Autoinflammatory Diseases ; Mesenchymal Stem Cell Transplantation
Language	English
Publishing date	2023-11-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242216040
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Article ; Online: Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches.

Zaripova, Lina N / Midgley, Angela / Christmas, Stephen E / Beresford, Michael W / Baildam, Eileen M / Oldershaw, Rachel A

Pediatric rheumatology online journal

2021 Volume 19, Issue 1, Page(s) 135

Abstract: Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. Depending on the number of joints affected, presence of ... ...

Abstract	Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. Depending on the number of joints affected, presence of extra-articular manifestations, systemic symptoms, serology and genetic factors, JIA is divided into oligoarticular, polyarticular, systemic, psoriatic, enthesitis-related and undifferentiated arthritis. This review provides an overview of advances in understanding of JIA pathogenesis focusing on aetiology, histopathology, immunological changes associated with disease activity, and best treatment options. Greater understanding of JIA as a collective of complex inflammatory diseases is discussed within the context of therapeutic interventions, including traditional non-biologic and up-to-date biologic disease-modifying anti-rheumatic drugs. Whilst the advent of advanced therapeutics has improved clinical outcomes, a considerable number of patients remain unresponsive to treatment, emphasising the need for further understanding of disease progression and remission to support stratification of patients to treatment pathways.
MeSH term(s)	Antirheumatic Agents/classification ; Antirheumatic Agents/pharmacology ; Arthritis, Juvenile/drug therapy ; Arthritis, Juvenile/etiology ; Arthritis, Juvenile/immunology ; Arthritis, Juvenile/physiopathology ; Child ; Disease Progression ; Humans ; Medication Therapy Management/trends ; Risk Assessment
Chemical Substances	Antirheumatic Agents
Language	English
Publishing date	2021-08-23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2279468-2
ISSN	1546-0096 ; 1546-0096
ISSN (online)	1546-0096
ISSN	1546-0096
DOI	10.1186/s12969-021-00629-8
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Article ; Online: The prioritization of symptom beliefs over illness beliefs: The development and validation of the Pain Perception Questionnaire for Young People.

Ghio, Daniela / Thomson, Wendy / Calam, Rachel / Ulph, Fiona / Baildam, Eileen M / Hyrich, Kimme / Cordingley, Lis

British journal of health psychology

2017 Volume 23, Issue 1, Page(s) 68–87

Abstract: Objectives: To investigate the suitability of the revised Illness Perception Questionnaire (IPQ-R) for use with adolescents with a long-term pain condition and to validate a new questionnaire for use with this age group.: Design: A three-phase mixed- ... ...

Abstract	Objectives: To investigate the suitability of the revised Illness Perception Questionnaire (IPQ-R) for use with adolescents with a long-term pain condition and to validate a new questionnaire for use with this age group. Design: A three-phase mixed-methods study. Methods: Phase 1 comprised in-depth qualitative analyses of audio-recorded cognitive interviews with 20 adolescents with juvenile idiopathic arthritis who were answering IPQ-R items. Transcripts were coded using framework analysis. A content analysis of their intended responses to individual items was also conducted. In Phase 2, a new questionnaire was developed and its linguistic and face validity were assessed with 18 adolescents without long-term conditions. In Phase 3, the construct validity of the new questionnaire was assessed with 240 adolescents with juvenile idiopathic arthritis. A subset of 43 adolescents completed the questionnaire a second time to assess test-retest reliability. All participants were aged 11-16 years. Results: Participants described both conceptual and response format difficulties when answering IPQ-R items. In response, the Pain Perception Questionnaire for Young People (PPQ-YP) was designed which incorporated significant modifications to both wording and response formats when compared with the IPQ-R. A principal component analysis of the PPQ-YP identified ten constructs in the new questionnaire. Emotional representations were separated into two constructs, responsive and anticipatory emotions. The PPQ-YP showed high test-retest reliability. Conclusions: Symptom beliefs appear to be more salient to adolescents with a long-term pain condition than beliefs about the illness as a whole. A new questionnaire to assess pain beliefs of adolescents was designed. Further validation work may be needed to assess its suitability for use with other pain conditions. Statement of contribution What is already known on this subject? Versions of the adult Revised Illness Perception Questionnaire (IPQ-R) have been adapted for adolescents and children by changing item wording; however, research to assess the degree to which the underlying IPQ-R constructs are relevant to adolescents with a long-term condition had not been performed. What the present study adds? In adolescents, beliefs about symptoms of their condition are more salient than beliefs about the illness as a whole. Question response formats for children and young people need to take account of age-specific abilities. A new questionnaire has been designed for adolescents with pain. It is theoretically congruent with the CS-SRM.
MeSH term(s)	Adolescent ; Arthritis, Juvenile/psychology ; Child ; Emotions ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Pain Perception ; Psychometrics ; Reproducibility of Results ; Surveys and Questionnaires
Language	English
Publishing date	2017-10-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Validation Study
ZDB-ID	2026500-1
ISSN	2044-8287 ; 1359-107X
ISSN (online)	2044-8287
ISSN	1359-107X
DOI	10.1111/bjhp.12275
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Article ; Online: Childrens' and parents' beliefs about childhood onset scleroderma are influenced by child age and physical function impairment.

Ennis, Holly / Herrick, Ariane L / Baildam, Eileen M / Richards, Helen L

Rheumatology (Oxford, England)

2012 Volume 51, Issue 7, Page(s) 1331–1333

MeSH term(s)	Adolescent ; Adult ; Aged ; Child ; Disability Evaluation ; Disabled Children ; Disease Progression ; Female ; Health Status ; Humans ; Incidence ; Male ; Middle Aged ; Motor Activity ; Parents ; Scleroderma, Systemic/epidemiology ; Scleroderma, Systemic/physiopathology ; Scleroderma, Systemic/rehabilitation ; Young Adult
Language	English
Publishing date	2012-07
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kes071
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Article ; Online: Different corticosteroid induction regimens in children and young people with juvenile idiopathic arthritis: the SIRJIA mixed-methods feasibility study.

Jones, Ashley P / Clayton, Dannii / Nkhoma, Gloria / Sherratt, Frances C / Peak, Matthew / Stones, Simon R / Roper, Louise / Young, Bridget / McErlane, Flora / Moitt, Tracy / Ramanan, Athimalaipet V / Foster, Helen E / Williamson, Paula R / Deepak, Samundeeswari / Beresford, Michael W / Baildam, Eileen M

Health technology assessment (Winchester, England)

2020 Volume 24, Issue 36, Page(s) 1–152

Abstract: Background: In the UK, juvenile idiopathic arthritis is the most common inflammatory disorder in childhood, affecting 10 : 100,000 children and young people aged < 16 years each year, with a population prevalence of around 1 : 1000. Corticosteroids are ... ...

Abstract	Background: In the UK, juvenile idiopathic arthritis is the most common inflammatory disorder in childhood, affecting 10 : 100,000 children and young people aged < 16 years each year, with a population prevalence of around 1 : 1000. Corticosteroids are commonly used to treat juvenile idiopathic arthritis; however, there is currently a lack of consensus as to which corticosteroid induction regimen should be used with various disease subtypes and severities of juvenile idiopathic arthritis. Objective: The main study objective was to determine the feasibility of conducting a randomised controlled trial to compare the different corticosteroid induction regimens in children and young people with juvenile idiopathic arthritis. Design: This was a mixed-methods study. Work packages included a literature review; qualitative interviews with children and young people with juvenile idiopathic arthritis and their families; a questionnaire survey and screening log to establish current UK practice; a consensus meeting with health-care professionals, children and young people with juvenile idiopathic arthritis, and their families to establish the primary outcome; a feasibility study to pilot data capture and to collect data for future sample size calculations; and a final consensus meeting to establish the final protocol. Setting: The setting was rheumatology clinics across the UK. Participants: Children, young people and their families who attended clinics and health-care professionals took part in this mixed-methods study. Interventions: This study observed methods of prescribing corticosteroids across the UK. Main outcome measures: The main study outcomes were the acceptability of a future trial for children, young people, their families and health-care professionals, and the feasibility of delivering such a trial. Results: Qualitative interviews identified differences in the views of children, young people and their families on a randomised controlled trial and potential barriers to recruitment. A total of 297 participants were screened from 13 centres in just less than 6 months. In practice, all routes of corticosteroid administration were used, and in all subtypes of juvenile idiopathic arthritis. Intra-articular corticosteroid injection was the most common treatment. The questionnaire surveys showed the varying clinical practice across the UK, but established intra-articular corticosteroids as the treatment control for a future trial. The primary outcome of choice for children, young people, their families and health-care professionals was the Juvenile Arthritis Disease Activity Score, 71-joint count. However, results from the feasibility study showed that, owing to missing blood test data, the clinical Juvenile Arthritis Disease Activity Score should be used. The Juvenile Arthritis Disease Activity Score, 71-joint count, and the clinical Juvenile Arthritis Disease Activity Score are composite disease activity scoring systems for juvenile arthritis. Two final trial protocols were established for a future randomised controlled trial. Limitations: Fewer clinics were included in this feasibility study than originally planned, limiting the ability to draw strong conclusions about these units to take part in future research. Conclusions: A definitive randomised controlled trial is likely to be feasible based on the findings from this study; however, important recommendations should be taken into account when planning such a trial. Future work: This mixed-methods study has laid down the foundations to develop the evidence base in this area and conducting a randomised control trial to compare different corticosteroid induction regimens in children and young people with juvenile idiopathic arthritis is likely to be feasible. Study registration: Current Controlled Trials ISRCTN16649996. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
MeSH term(s)	Adolescent ; Adrenal Cortex Hormones/administration & dosage ; Arthritis, Juvenile/drug therapy ; Child ; Clinical Protocols/standards ; Drug Administration Routes ; Feasibility Studies ; Female ; Humans ; Injections, Intra-Articular ; Male ; Outcome Assessment, Health Care ; Practice Patterns, Physicians'/standards ; Randomized Controlled Trials as Topic ; Surveys and Questionnaires/statistics & numerical data ; United Kingdom
Chemical Substances	Adrenal Cortex Hormones
Language	English
Publishing date	2020-08-06
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2006765-3
ISSN	2046-4924 ; 1366-5278
ISSN (online)	2046-4924
ISSN	1366-5278
DOI	10.3310/hta24360
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Article ; Online: Recent developments in disease activity indices and outcome measures for juvenile idiopathic arthritis.

McErlane, Flora / Beresford, Michael W / Baildam, Eileen M / Thomson, Wendy / Hyrich, Kimme L

Rheumatology (Oxford, England)

2013 Volume 52, Issue 11, Page(s) 1941–1951

Abstract: There has been a concerted and important international effort to develop and validate disease activity and outcome instruments specific to JIA in recent years. This review aims to describe the disease assessment indices important to routine clinical care ...

Abstract	There has been a concerted and important international effort to develop and validate disease activity and outcome instruments specific to JIA in recent years. This review aims to describe the disease assessment indices important to routine clinical care and integral to the design of outcome studies and clinical trials in JIA. In view of the increasing number of JIA clinical studies and clinical trials, together with a number of national and international paediatric biologic registers, it is important that knowledge of these new outcome measures is widespread, such that results can be placed in a meaningful context.
MeSH term(s)	Arthritis, Juvenile/diagnosis ; Arthritis, Juvenile/therapy ; Disability Evaluation ; Humans ; Outcome Assessment, Health Care/methods ; Patient Outcome Assessment ; Severity of Illness Index
Language	English
Publishing date	2013-04-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/ket150
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Article: Macrophage activation syndrome is hemophagocytic lymphohistiocytosis--need for the right terminology.

Ramanan, Athimalaipet V / Baildam, Eileen M

The Journal of rheumatology

2002 Volume 29, Issue 5, Page(s) 1105; author reply 1105

MeSH term(s)	Histiocytosis, Non-Langerhans-Cell/chemically induced ; Histiocytosis, Non-Langerhans-Cell/immunology ; Humans ; Macrophage Activation ; Terminology as Topic
Language	English
Publishing date	2002-05
Publishing country	Canada
Document type	Comment ; Letter
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
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Article ; Online: Clinical features of childhood localized scleroderma in an incidence cohort.

Herrick, Ariane L / Ennis, Holly / Bhushan, Monica / Silman, Alan J / Baildam, Eileen M

Rheumatology (Oxford, England)

2011 Volume 50, Issue 10, Page(s) 1865–1868

Abstract: Objectives: Our aim was to describe clinical features and pattern of care in children with localized scleroderma presenting to secondary care during a 25-month incidence study.: Methods: Eighty-seven patients were identified, and clinical features, ... ...

Abstract	Objectives: Our aim was to describe clinical features and pattern of care in children with localized scleroderma presenting to secondary care during a 25-month incidence study. Methods: Eighty-seven patients were identified, and clinical features, serum autoantibodies, current treatment and outcome at 12 months were documented. Results: Fifty-eight (67%) had linear scleroderma, 25 (29%) non-linear morphoea and 4 (4%) a mixed pattern. Of the 58 patients with linear scleroderma, 29 (50%) presented with lesions of the trunk and/or limbs only, 26 (45%) with face-head localization only and 3 (5%) with both. Thirteen (15%) had extracutaneous features and 16 (43%) out of 37 were ANA positive. At 12 months, 59% were on MTX. At 12 months, 51 (65%) were improved/resolved, 14 (18%) were unchanged and 13 (17%) had deteriorated. Conclusion: Key findings included the high prevalence of face-head involvement in those with linear disease, and the high prevalence of extracutaneous disease and of ANA positivity. After 12 months, most patients improved according to clinician's opinion.
MeSH term(s)	Back ; Child ; Cohort Studies ; Extremities ; Face ; Female ; Humans ; Immunosuppressive Agents/therapeutic use ; Male ; Methotrexate/therapeutic use ; Scleroderma, Localized/diagnosis ; Scleroderma, Localized/drug therapy ; Scleroderma, Localized/epidemiology ; Severity of Illness Index ; Skin/pathology ; Surveys and Questionnaires
Chemical Substances	Immunosuppressive Agents ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2011-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/ker142
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Article ; Online: United Kingdom survey of current management of juvenile localized scleroderma.

Hawley, Daniel P / Pain, Clare E / Baildam, Eileen M / Murphy, Ruth / Taylor, Aileen E M / Foster, Helen E

Rheumatology (Oxford, England)

2014 Volume 53, Issue 10, Page(s) 1849–1854

Abstract: Objectives: Juvenile localized scleroderma (JLS) is a rare condition that is often difficult to assess and for which a variety of monitoring tools have been described. We aimed to describe how monitoring tools are used and perceived by clinicians in the ...

Abstract	Objectives: Juvenile localized scleroderma (JLS) is a rare condition that is often difficult to assess and for which a variety of monitoring tools have been described. We aimed to describe how monitoring tools are used and perceived by clinicians in the UK, to ascertain treatments used for JLS and to provide a description of transition arrangements to adult care. Methods: An e-survey of UK paediatric rheumatologists and dermatologists managing children and young people (CYP) with JLS was distributed using the national organisations representing these clinician groups. We asked respondents for their views and experience using 15 JLS monitoring tools, about transition services and about treatments used. Results: Thirty-five dermatologists and 13 paediatric rheumatologists responded. Paediatric rheumatologists managed more CYP with JLS than dermatologists (median 16-20 and 3, respectively). Transition arrangements were reported by 43% of dermatologists and 91% of paediatric rheumatologists. Medical photography was the most frequently regularly used monitoring tool (73% respondents). The modified Rodnan skin score was the skin score used most commonly: 33% of paediatric rheumatologists and 3% of dermatologists reported using this tool frequently. Topical treatments and ultraviolet light were used by 49-80% of dermatologists and 0-8% paediatric rheumatologists. Biologic drugs and CYC were used by 0-3% of dermatologists and 31-46% of paediatric rheumatologists. Conclusion: How monitoring tools are accessed, used and perceived by paediatric rheumatologists and dermatologists in the UK varies between and within clinician groups, as do treatment prescribing patterns and transition arrangements. These differences will impact on the feasibility of conducting multicentre clinical trials and on standardising clinical care.
MeSH term(s)	Administration, Topical ; Adolescent ; Child ; Glucocorticoids/administration & dosage ; Glucocorticoids/therapeutic use ; Health Care Surveys ; Humans ; Pediatrics ; Practice Patterns, Physicians' ; Scleroderma, Localized/diagnosis ; Scleroderma, Localized/drug therapy ; Scleroderma, Localized/therapy ; Ultraviolet Therapy
Chemical Substances	Glucocorticoids
Language	English
Publishing date	2014-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keu212
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Article ; Online: Patterns of pain over time among children with juvenile idiopathic arthritis.

Rashid, Amir / Cordingley, Lis / Carrasco, Roberto / Foster, Helen E / Baildam, Eileen M / Chieng, Alice / Davidson, Joyce E / Wedderburn, Lucy R / Ioannou, Yiannis / McErlane, Flora / Verstappen, Suzanne M M / Hyrich, Kimme L / Thomson, Wendy

Archives of disease in childhood

2017 Volume 103, Issue 5, Page(s) 437–443

Abstract: Objectives: Pain is a very common symptom of juvenile idiopathic arthritis (JIA). Disease activity alone cannot explain symptoms of pain in all children, suggesting other factors may be relevant. The objectives of this study were to describe the ... ...

Abstract	Objectives: Pain is a very common symptom of juvenile idiopathic arthritis (JIA). Disease activity alone cannot explain symptoms of pain in all children, suggesting other factors may be relevant. The objectives of this study were to describe the different patterns of pain experienced over time in children with JIA and to identify predictors of which children are likely to experience ongoing pain. Methods: This study used longitudinal-data from patients (aged 1-16 years) with new-onset JIA. Baseline and up to 5-year follow-up pain data from the Childhood Arthritis Prospective Study (CAPS) were used. A two-step approach was adopted. First, pain trajectories were modelled using a discrete mixture model. Second, multinomial logistic regression was used to determine the association between variables and trajectories. Results: Data from 851 individuals were included (4 years, median follow-up). A three-group trajectory model was identified: consistently low pain (n=453), improved pain (n=254) and consistently high pain (n=144). Children with improved pain or consistently high pain differed on average at baseline from consistently low pain. Older age at onset, poor function/disability and longer disease duration at baseline were associated with consistently high pain compared with consistently low pain. Early increases in pain and poor function/disability were also associated with consistently high pain compared with consistently low pain. Conclusions: This study has identified routinely collected clinical factors, which may indicate those individuals with JIA at risk of poor pain outcomes earlier in disease. Identifying those at highest risk of poor pain outcomes at disease onset may enable targeted pain management strategies to be implemented early in disease thus reducing the risk of poor pain outcomes.
MeSH term(s)	Adolescent ; Age Factors ; Arthritis, Juvenile/complications ; Child ; Child, Preschool ; Chronic Pain/etiology ; Chronic Pain/therapy ; Disability Evaluation ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Pain/etiology ; Pain Management/methods ; Pain Measurement/methods ; Prognosis ; Risk Factors
Language	English
Publishing date	2017-11-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	524-1
ISSN	1468-2044 ; 0003-9888 ; 1359-2998
ISSN (online)	1468-2044
ISSN	0003-9888 ; 1359-2998
DOI	10.1136/archdischild-2017-313337
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