Matthew Morgan

Hull York Medical School

Background: Venous thromboembolism (VTE) is a common complication in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) and confers significant morbidity and mortality. Both acute and past cytomegalovirus (CMV) infection have been identified as risk factors for VTE in immunocompetent and immunosuppressed individua...

Objective Patients with ANCA associated vasculitis (AAV) experience high levels of fatigue, despite disease remission. This study assessed the feasibility and acceptability of a definitive randomised controlled trial of a behavioural-based physical activity intervention to support fatigue self-management in AAV patients. Methods AAV patients in di...

Objective Fatigue is common and burdensome in ANCA-associated vasculitis (AAV). This study aimed to understand how fatigue changes over time following treatment initiation and determine whether individuals with the poorest prognosis can be robustly identified. Methods 149 patients with AAV and new onset disease recruited to two clinical trials (RI...

Background Intravenous pulse methylprednisolone (MP) is commonly included in the management of severe ANCA associated vasculitis (AAV) despite limited evidence of benefit. We aimed to evaluate outcomes in patients who had, or had not received MP, along with standard therapy for remission induction in severe AAV. Methods We retrospectively studied...

Introduction: Fatigue is a major cause of morbidity, limiting quality of life, in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The aetiology of fatigue is multifactorial; biological and psychosocial mediators, such as sleep deprivation, pain and anxiety and depression, are important and may be improved by increasi...

Background: Cardiovascular disease is a leading cause of death in ANCA-associated vasculitis (AAV). An expansion of CD4+CD28null T cells is seen mainly in cytomegalovirus (CMV)-seropositive individuals and has been linked to increased cardiovascular disease risk in other conditions. The aims of this study were to phenotype CD4+CD28null T cells in...

Background: Infection is the leading cause of death in ANCA-associated vasculitis (AAV). Expansion of CD4+CD28null T-cells is associated with increased risk of infection and mortality, but is only present in cytomegalovirus-seropositive individuals. We hypothesised that subclinical cytomegalovirus reactivation drives CD4+CD28null T-cell expansion;...

Patients with chronic kidney disease (CKD) have an increased risk of infection and poorer responses to vaccination. This suggests that CKD patients have an impaired responsiveness to all antigens, even those first encountered before CKD onset. To examine this we evaluated antibody responses against two childhood vaccine antigens, tetanus (TT) and d...

Objectives This study aimed to investigate the impact of research training funded via the National Health Service (NHS) on medical trainees compared with traditional clinical research training fellowships (CRTFs). Design, setting and participants Online survey of 221 clinical trainees who had completed a period of research during their clinical tr...

Background Relapse of disease is frequent in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). It is unclear whether persistent ANCA when starting maintenance therapy increases the risk of relapse. We examined the association between ANCA status and relapse in two randomised controlled trials. Methods ANCA-positive patients in...

Background Relapse of disease is frequent in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). It is unclear whether persistent ANCA when starting maintenance therapy increases the risk of relapse. We examined the association between ANCA status and relapse in two randomised controlled trials. Methods ANCA-positive patients in...

Background CD4+CD28– T-cell expansion is linked to increased infection and mortality in patients with ANCA-associated vasculitis (AAV), and cardiovascular disease in other inflammatory conditions. We aimed to characterise these cells in AAV, assess their contribution to arterial stiffness, a marker of cardiovascular disease risk, and in a proof-of-...

Background: The ANCA-associated vasculitides (AAV) are systemic autoimmune inflammatory disorders characterised by necrotising inflammation affecting small to medium-sized blood vessels. Despite improvements in survival, infection and cardiovascular disease remain leading causes of morbidity and mortality. Considerable evidence suggests that CD4 +...

Objective: This study investigated differences in cardiorespiratory fitness, muscular function, perceived exertion, and anxiety/depression between patients and healthy controls (HCs) and assessed which of these variables may account for the fatigue experienced by patients. Methods: Fatigue was measured in 48 antineutrophil cytoplasmic antibody-a...

Objectives Patients with systemic vasculitis (SV) have an increased risk of all-cause mortality, often due to infection, compared to the healthy population. We investigated whether humoral response to vaccination and biomarkers of immune dysfunction were associated with infection and death.Methods Patients with SV in remission were vaccinated with...

Rituximab and glucocorticoids are a non-inferior alternative to cyclophosphamide and glucocorticoid therapy for induction of remission in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) patients with moderate renal disease. The efficacy and safety of this approach in patients with severe renal impairment are unknown. We repor...

Rituximab (RTX) is approved for remission induction in ANCA associated vasculitis (AAV). However, data on use of RTX in patients with severe renal disease is lacking. We conducted a retrospective multi-center study to evaluate the efficacy and safety of RTX with glucocorticoids (GC) with and without use of concomitant cyclophosphamide (CYC) for rem...

Granulomatosis with polyangiitis (GPA) is associated with circulating immunoglobulin (Ig) G anti-proteinase 3 specific (anti-PR3) anti-neutrophil cytoplasm antibodies (ANCA) which activate cytokine primed neutrophils via Fcgamma receptors. ANCA are class switched IgG antibodies implying T cell help in their production. Glycosylation of IgG Fc, unde...

The RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 12 months; however, immunosuppression maintenance requirements and longer-term outcomes after rituximab in ANCA-associated renal vasculitis are unknown....

Cardiovascular risk is increased in the anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV). CD4+CD28- T cells are expanded in patients with AAV who are seropositive for cytomegalovirus (CMV), and are associated with increased mortality. CMV seropositivity in other conditions is associated with arterial stiffness, a marker of ca...

Pregnancy in patients with anti-neutrophil cytoplasm antibody–associated vasculitis is reportedly associated with a high risk of fetal and maternal complications. Here we describe the outcome of pregnancies in patients with granulomatosis with polyangiitis and microscopic polyangiitis at five centers in the United Kingdom using a retrospective case...

Background There is a paucity of data on the outcome of pregnancy in patients with primary systemic vasculitis. The limited evidence available suggests frequent complications such as first-trimester miscarriages, pre-term births, premature rupture of membranes and relapse of disease resulting in fetal and maternal death. Many of these studies are o...

Endothelial cell (EC) dysfunction (ECD) occurs in antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV)1 2 but improves with anti-tumour necrosis factor α (anti-TNFα) treatment,1 suggesting a key role for this cytokine. TNFα and interleukin 1 can induce secretion of acid sphingomyelinase (ASM) from ECs,3 4 which are the major so...

The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (...

The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegaloviru...

To determine a role for antineutrophil cytoplasmic antibody (ANCA)-activated neutrophils in promoting B cell survival through the release of B lymphocyte stimulator (BLyS). Neutrophil BLyS expression was measured by flow cytometry. Concentrations of BLyS in cell supernatants and donor serum samples were measured by ELISA. Cell survival assays were...

Small studies have linked α1 antitrypsin (α1AT) deficiency to patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). To test the validity and the mechanism of this association between α1AT and AAV. The distribution of α1AT deficiency alleles Z and S was compared between 856 White Europeans with AAV and 1505 geograph...

Expanded populations of CD4+CD28- T cells with a cytotoxic phenotype have been repeatedly reported in patients with granulomatosis with polyangiitis (Wegener's) (GPA). In healthy individuals expansion of this T cell population follows cytomegalovirus (CMV) infection. We undertook this study to investigate whether CMV infection may be responsible fo...

BACKGROUND: Caveolae are flask-shaped invaginations of plasma cell membranes found in most human tissues, in particular endothelial cells, adipocytes, muscle cells, fibroblasts and macrophages. Caveolin-1 (CAV1) is an essential structural component of caveolae, and has been implicated in the pathogenesis of fibrotic and inflammatory diseases as wel...

The routine assessment of cellular alloimmunity to guide therapy is of perennial interest because this limb of the immune system is the main target of current transplant immunosuppression. That this has not as yet been realized in clinical practice reflects the difficulty of developing a standardized assay that accounts for the high degree of polym...

Tumour necrosis factor-α (TNF) is implicated in the pathogenesis of anti-neutrophil cytoplasm antibody-associated vasculitis (AAV). Current immunosuppressive therapy is associated with considerable morbidity and mortality. Anti-TNF antibody therapy (infliximab) may help control AAV by providing more targeted immunosuppression and allow reductions i...

Baseline characteristics and outcome in the East Kent validation cohort.

Age- and sex- adjusted correlations between those continuous markers found to predict either ESRD or death in the CRIB cohort.

Relevance of baseline characteristics to ESRD in the CRIB cohort, given age and sex.

Relevance of baseline characteristics to death in the CRIB cohort, given age and sex.

Monoclonal gammopathies frequently cause renal disease, but they may be an incidental finding. Assessment of renal pathology in the context of renal dysfunction and a monoclonal gammopathy therefore serves as a useful diagnostic tool and, in addition, provides prognostic information. There is, however, a theoretical risk of increased hemorrhagic co...

Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD). Prospective cohort study with validation in a separate cohort. Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (m...

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation (BMT) the immunopathogenesis of which is not well understood. Humoral and cellular immunity are both implicated, patients express a range of autoantibodies, but the targets of cellular immunity are not well defined. Autologous human leukocyte...

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises a group of systemic inflammatory vasculitides associated with circulating autoantibodies directed against the neutrophil granule components proteinase 3 and myeloperoxidase. ANCA interact with their target antigens on cytokine primed neutrophils, causing neutrophil activ...

Cyclophosphamide induction regimens for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are effective in 70 to 90% of patients, but they are associated with high rates of death and adverse events. Treatment with rituximab has led to remission rates of 80 to 90% among patients with refractory ANCA-associated vasculitis and may be sa...

An increased proportion of CD4(+) CD25(+) T cells has been reported in Wegener's granulomatosis (WG) and may represent an accumulation of regulatory T cells (Treg). CD25 is also expressed on recently activated effector T cells. We have determined the relative proportion of these subsets in a large patient cohort. The fraction of Treg in peripheral...

In Systemic Lupus Erythematosus (SLE) resistant to conventional therapy anti-CD20 (Rituximab) therapy has been successful with about 80% of patients responding in most open label case series. However, about 30% of patients develop anti-drug antibodies (ADA), which may have a detrimental effect on the efficacy of the drug. Identification of the pres...

To explore the risk of cardiovascular disease in patients with antineutrophil cytoplasmic antibody-associated vasculitides (AAVs) and to assess contributing risk factors. In a retrospective matched-pair cohort study, 113 of 131 patients with AAVs from a vasculitis clinic registry were matched 1:1 for renal function, age at diagnosis, sex, smoking s...

We recently reported human CD4+ T lymphocyte responses to peptide epitopes derived from sequences of class I HLA that exhibit little polymorphism, some that are identical to self and many of which bind promiscuously to MHC class II ('public T cell epitopes' PTE). This contrasts with other studies in which there is an assumption that epitopes arise...

Wegener's granulomatosis, microscopic polyangiitis, and renal limited vasculitis are associated with circulating anti-neutrophil cytoplasm antibodies and are an important cause of rapidly progressive glomerulonephritis. This review gives an account of recent advances in the understanding of the pathogenesis underlying these conditions and how these...

In antineutrophil cytoplasm autoantibody (ANCA)-associated systemic vasculitis (ASV), autoantibody-induced neutrophil activation is believed to cause organ damage. In vitro, tumor necrosis factor alpha (TNFalpha) primes neutrophils for ANCA stimulation and TNFalpha blockade has been successfully used to treat ASV. Nonetheless, irreversible organ da...

Neutrophils are important effector cells during inflammatory responses. Further, their many functions, controlled by cell surface receptors and intracellular signalling pathways, provide multiple opportunities for modulating unwanted responses. Potential mediators and drugs to achieve these ends are under development and will likely provide new ins...

The primary systemic vasculitides are a rare group of inflammatory disorders, where damage is directed against the blood vessels. They range in severity from acute self-limiting illness to chronic life and organ threatening diseases requiring long-term treatment with toxic immunosuppressive regimes. None of them have specific tests and few have har...

Antineutrophil cytoplasm antibodies (ANCA) activate neutrophils to undergo a series of coordinated interactions, leading to transendothelial migration, eventually culminating in vascular destruction. The molecular events underlying neutrophil recruitment in ANCA-associated vasculitis need to be defined to enable effective therapeutic manipulation....

The potential therapies for antineutrophil cytoplasm antibody-associated vasculitis (AAV) have increased over the past 10 years. The aims of therapy are to induce remission of disease, maintain remission, and prevent relapse. Cyclophosphamide and glucocorticoids remain the standard therapy, but the toxicity of cyclophosphamide limits its use, and i...