Publications
562 results found
Koutroutsos K, Willicombe M, Charif R, et al., 2014, Alemtuzumab Induction and Post-Transplant Glomerulonephritis in Kidney Transplantation., World Transplant Congress, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 534-535, ISSN: 0041-1337
Tanna A, Guarino L, Tam FWK, et al., 2014, Long-term outcome of anti-neutrophil cytoplasm antibody-associated glomerulonephritis: evaluation of the international histological classification and other prognostic factors, Nephrology Dialysis Transplantation, Vol: 30, Pages: 1185-1192, ISSN: 1460-2385
Background Anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis with renal involvement requires treatment with potentially toxic drugs to reduce morbidity and mortality, and there is a major challenge to determine clinical and histological features predictive of renal prognosis. The aim of our study was to evaluate the use of the 2010 international histological classification for ANCA-associated glomerulonephritis (AAGN) as a predictor of renal outcome when used in conjunction with other prognostic factors.Methods One hundred and four patients with AAGN treated at our centre were included: 23 were classified as focal, 26 as crescentic, 48 as mixed and 7 as sclerotic. Renal outcomes were based on estimated glomerular filtration rate (eGFR) at 1 and 5 years, and on renal survival.Results By univariate analysis, patients in the focal class had the best renal outcome, those in the sclerotic class the worst outcome, and those in the mixed and crescentic classes had intermediate renal survival. There was no significant difference in outcome between the mixed and crescentic classes. In multivariate models, histological class did not improve model fit or associate with renal outcome after adjusting for established prognostic factors. Lower percentage of normal glomeruli, greater degree of tubular atrophy (TA), MPO-ANCA positivity, increasing age and lower starting eGFR, all correlated with poorer renal outcomes.Conclusions We conclude that, in our cohort of patients, the international histological classification is predictive of renal outcome in AAGN, but did not appear to be additionally informative over other established prognostic factors in multivariate analysis. However, it may be of value to combine the current histological classification with other established parameters, such as TA and percentage normal glomeruli.
McLean A, Brookes P, Charif R, et al., 2014, One Agent-Once a Day: 2 Year Outcomes of a Prospective Randomized Trial of Once Daily (Extended Release) Tacrolimus Maintenance Monotherapy vs Twice Daily (Standard Release) Tacrolimus After Alemtuzumab Induction & Early Steroid Cessation (TAESR Trial). Rejection and Variation in Tacrolimus Levels, World Transplant Congress, Publisher: WILEY-BLACKWELL, Pages: 536-536, ISSN: 1600-6135
Clarke C, Lawrence C, Willicombe M, et al., 2014, IgG Donor Specific Antibodies [DSAs] in Patients With Transplant Glomerulopathy [TG] Are Associated With Inferior Allograft Survival, World Transplant Congress, Publisher: WILEY-BLACKWELL, Pages: 440-440, ISSN: 1600-6135
Willicombe M, Roufosse C, Moran L, et al., 2014, Significance of Tubuloreticular Inclusions in Renal Allografts., World Transplant Congress, Publisher: WILEY-BLACKWELL, Pages: 529-529, ISSN: 1600-6135
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- Citations: 1
McLean A, Chan K, Roufosse C, et al., 2014, 5-Year Outcomes of a Randomized Prospective Trial of Tacrolimus Maintenance Monotherapy After Alemtuzumab Induction and Early Steroid Withdrawal in Kidney Transplantation: Rejection, HLA Antibody Formation, and Recurrent Disease., World Transplant Congress, Publisher: WILEY-BLACKWELL, Pages: 114-114, ISSN: 1600-6135
McAdoo S, Bhangal G, Smith J, et al., 2014, Spleen Tyrosine Kinase (SYK) Expression in Antibody-Mediated Renal Allograft Rejection, World Transplant Congress, Publisher: WILEY-BLACKWELL, Pages: 513-514, ISSN: 1600-6135
Smith J, Syed A, Bhangal G, et al., 2014, Treatment With a Spleen Tyrosine Kinase Inhibitor Reduced Inflammation and Protected Kidney Function in Experimental Renal Allograft Rejection., World Transplant Congress, Publisher: WILEY-BLACKWELL, Pages: 27-27, ISSN: 1600-6135
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- Citations: 1
Koutroutsos K, Willicombe M, Charif R, et al., 2014, Alemtuzumab Induction and Post-Transplant Glomerulonephritis in Kidney Transplantation, World Transplant Congress, Publisher: WILEY-BLACKWELL, Pages: 534-535, ISSN: 1600-6135
Carlucci F, Ishaque A, Ling GS, et al., 2014, C1Q REGULATES THE TLR7-MEDIATED INFLAMMATORY RESPONSE BY PRISTANE-PRIMED MACROPHAGES: IMPLICATIONS FOR PRISTANE-INDUCED LUPUS (PIL), 15th Annual European Congress of Rheumatology (EULAR), Publisher: BMJ PUBLISHING GROUP, Pages: 861-861, ISSN: 0003-4967
Sattler S, Ling G-S, Xu D, et al., 2014, IL-10-producing regulatory B cells induced by IL-33 (Breg(IL-33)) effectively attenuate mucosal inflammatory responses in the gut, Journal of Autoimmunity, Vol: 50, Pages: 107-122, ISSN: 0896-8411
Regulatory B cells (Breg) have attracted increasing attention for their roles in maintaining peripheral tolerance. Interleukin 33 (IL-33) is a recently identified IL-1 family member, which leads a double-life with both pro- and anti-inflammatory properties. We report here that peritoneal injection of IL-33 exacerbated inflammatory bowel disease in IL-10-deficient (IL-10−/−) mice, whereas IL-33-treated IL-10-sufficient (wild type) mice were protected from the disease induction. A phenotypically unconventional subset(s) (CD19+CD25+CD1dhiIgMhiCD5-CD23-Tim-1-) of IL-10 producing Breg-like cells (BregIL-33) was identified responsible for the protection. We demonstrated further that BregIL-33 isolated from these mice could suppress immune effector cell expansion and functions and, upon adoptive transfer, effectively blocked the development of spontaneous colitis in IL-10−/− mice. Our findings indicate an essential protective role, hence therapeutic potential, of BregIL-33 against mucosal inflammatory disorders in the gut.
Coppo R, Troyanov S, Bellur S, et al., 2014, Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments, Kidney International, Vol: 86, Pages: 828-836, ISSN: 1523-1755
The Oxford Classification of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as independent predictors of outcome. Whether it applies to individuals excluded from the original study and how therapy influences the predictive value of pathology remain uncertain. The VALIGA study examined 1147 patients from 13 European countries that encompassed the whole spectrum of IgAN. Over a median follow-up of 4.7 years, 86% received renin–angiotensin system blockade and 42% glucocorticoid/immunosuppressive drugs. M, S, and T lesions independently predicted the loss of estimated glomerular filtration rate (eGFR) and a lower renal survival. Their value was also assessed in patients not represented in the Oxford cohort. In individuals with eGFR less than 30 ml/min per 1.73 m2, the M and T lesions independently predicted a poor survival. In those with proteinuria under 0.5 g/day, both M and E lesions were associated with a rise in proteinuria to 1 or 2 g/day or more. The addition of M, S, and T lesions to clinical variables significantly enhanced the ability to predict progression only in those who did not receive immunosuppression (net reclassification index 11.5%). The VALIGA study provides a validation of the Oxford classification in a large European cohort of IgAN patients across the whole spectrum of the disease. The independent predictive value of pathology MEST score is reduced by glucocorticoid/immunosuppressive therapy.
Medjeral-Thomas N, Malik TH, Patel MP, et al., 2014, A novel CFHR5 fusion protein causes C3 glomerulopathy in a family without Cypriot ancestry, Kidney International, Vol: 85, Pages: 933-937, ISSN: 0085-2538
C3 glomerulopathy describes glomerular pathology associated with predominant deposition of complement C3 including dense deposit disease and C3 glomerulonephritis. Familial C3 glomerulonephritis has been associated with rearrangements affecting the complement factor H–related (CFHR) genes. These include a hybrid CFHR3-1 gene and an internal duplication within the CFHR5 gene. CFHR5 nephropathy, to date, occurred exclusively in patients with Cypriot ancestry, and is associated with a heterozygous internal duplication of the CFHR5 gene resulting in duplication of the exons encoding the first two domains of the CFHR5 protein. Affected individuals possess both the wild-type nine-domain CFHR5 protein (CFHR512-9) and an abnormally large mutant CFHR5 protein in which the initial two protein domains are duplicated (CFHR51212-9). We found CFHR51212-9 in association with familial C3 glomerulonephritis in a family without Cypriot ancestry. The genomic rearrangement was distinct from that seen in Cypriot CFHR5 nephropathy. Our findings strengthen the association between CFHR51212-9 and familial C3 glomerulonephritis and recommend screening for CFHR51212-9 in patients with C3 glomerulopathy irrespective of ethnicity. Since CFHR51212-9 can result from at least two genomic rearrangements, screening is most readily achieved through analysis of CFHR5 protein.
Willicombe M, Roufosse C, Brookes P, et al., 2014, Acute Cellular Rejection: Impact of Donor-Specific Antibodies and C4d, TRANSPLANTATION, Vol: 97, Pages: 433-439, ISSN: 0041-1337
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- Citations: 29
McAdoo SP, Tanna A, McDaid J, et al., 2014, SYK inhibition in experimental autoimmune vasculitis and its glomerular expression in ANCA-associated vasculitis, LANCET, Vol: 383, Pages: 72-72, ISSN: 0140-6736
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- Citations: 3
Baudino L, Sardini A, Ruseva MM, et al., 2014, C3 opsonization regulates endocytic handling of apoptotic cells resulting in enhanced T-cell responses to cargo-derived antigens, Proceedings of the National Academy of Sciences of the United States of America, Vol: 111, Pages: 1503-1508, ISSN: 0027-8424
Ling GS, Bennett J, Woollard KJ, et al., 2014, Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages, Nature Communications, Vol: 5, Pages: 1-12, ISSN: 2041-1723
Tuned and distinct responses of macrophages and dendritic cells to Toll-like receptor 4 (TLR4) activation induced by lipopolysaccharide (LPS) underpin the balance between innate and adaptive immunity. However, the molecule(s) that confer these cell-type-specific LPS-induced effects remain poorly understood. Here we report that the integrin αM (CD11b) positively regulates LPS-induced signalling pathways selectively in myeloid dendritic cells but not in macrophages. In dendritic cells, which express lower levels of CD14 and TLR4 than macrophages, CD11b promotes MyD88-dependent and MyD88-independent signalling pathways. In particular, in dendritic cells CD11b facilitates LPS-induced TLR4 endocytosis and is required for the subsequent signalling in the endosomes. Consistent with this, CD11b deficiency dampens dendritic cell-mediated TLR4-triggered responses in vivo leading to impaired T-cell activation. Thus, by modulating the trafficking and signalling functions of TLR4 in a cell-type-specific manner CD11b fine tunes the balance between adaptive and innate immune responses initiated by LPS.
Medjeral-Thomas NR, O'Shaughnessy MM, O'Regan JA, et al., 2014, C3 Glomerulopathy: Clinicopathologic Features and Predictors of Outcome, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 9, Pages: 46-53, ISSN: 1555-9041
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- Citations: 144
Pickering MC, D'Agati VD, Nester CM, et al., 2013, C3 glomerulopathy: consensus report, Kidney International, Vol: 84, Pages: 1079-1089, ISSN: 0085-2538
C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty immunoglobulin deposition. In August 2012, an invited group of experts (comprising the authors of this document) in renal pathology, nephrology, complement biology, and complement therapeutics met to discuss C3 glomerulopathy in the first C3 Glomerulopathy Meeting. The objectives were to reach a consensus on: the definition of C3 glomerulopathy, appropriate complement investigations that should be performed in these patients, and how complement therapeutics should be explored in the condition. This meeting report represents the current consensus view of the group.
Reynolds J, Preston GA, Pressler BM, et al., 2013, Autoimmunity to the alpha 3 chain of type IV collagen is triggered by 'autoantigen complementarity', Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 48-49, ISSN: 0019-2805
Narayan S, Cook HT, Pickering MC, et al., 2013, <i>N</i>-acetylmannosamine (ManNAc) supplementation of drinking water does not protect mice from nephrotoxic nephritis or complement-mediated renal injury, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 77-77, ISSN: 0019-2805
Asgari E, Le Friec G, Yamamoto H, et al., 2013, C3a modulates IL-1β secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation, BLOOD, Vol: 122, Pages: 3473-3481, ISSN: 0006-4971
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- Citations: 223
Barbour TD, Pickering MC, Cook HT, 2013, Dense Deposit Disease and C3 Glomerulopathy, SEMINARS IN NEPHROLOGY, Vol: 33, Pages: 493-507, ISSN: 0270-9295
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- Citations: 42
Rusai K, Zaller V, Szilagyi A, et al., 2013, A rare case: childhood-onset C3 glomerulonephritis due to homozygous factor H deficiency., CEN Case Rep, Vol: 2, Pages: 234-238, ISSN: 2192-4449
C3 glomerulopathy is a recently described pathological entity including dense deposit disease and C3 glomerulonephritis (C3GN). In some cases, C3 glomerulopathy is associated with defects or even complete deficiency of factor H. However, complete factor H deficiency among patients with C3GN is rare, and paediatric cases have not yet been described. Here, we report a child with homozygous factor H deficiency who presented with haematuria and minor proteinuria, together with undetectable plasma C3 levels, at the age of 10 years. Kidney biopsy demonstrated C3GN. Detailed complement analysis revealed complete factor H deficiency due to a homozygous CFH mutation. Furthermore, there was a complete deletion of CFHR-1/-3. During follow-up, the patient has had recurrent episodes of macro-haematuria and minor proteinuria, but during 4 years of follow-up, no deterioration of renal function has been observed. Mutations of factor H in C3GN have been described; however, complete CFH deficiency is rare in these patients. Furthermore, clinical presentation usually occurs in adulthood. Therefore, this case presents a rare manifestation of the disease and might contribute to the early detection of similar cases also in childhood.
D'Souza Z, McAdoo SP, Smith J, et al., 2013, Experimental crescentic glomerulonephritis: a new bicongenic rat model, DISEASE MODELS & MECHANISMS, Vol: 6, Pages: 1477-1486, ISSN: 1754-8403
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- Citations: 10
Santos-Nunez E, Brookes P, Willicombe M, et al., 2013, De novo DQ DSA post renal transplantation: incidence and outcomes, INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Vol: 40, Pages: 403-404, ISSN: 1744-3121
Bravou V, Galliford J, McLean A, et al., 2013, A case of chronic antibody-mediated rejection in the making, CLINICAL NEPHROLOGY, Vol: 80, Pages: 306-309, ISSN: 0301-0430
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- Citations: 2
Condon MB, Ashby D, Pepper RJ, et al., 2013, Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids, ANNALS OF THE RHEUMATIC DISEASES, Vol: 72, Pages: 1280-1286, ISSN: 0003-4967
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- Citations: 284
Barbour TD, Pickering MC, Cook HT, 2013, Recent insights into C3 glomerulopathy, Nephrology Dialysis Transplantation, Vol: 28, Pages: 1685-1693, ISSN: 1460-2385
‘C3 glomerulopathy’ is a recent disease classification comprising several rare types of glomerulonephritis (GN), including dense deposit disease (DDD), C3 glomerulonephritis (C3GN) and CFHR5 nephropathy. These disorders share the key histological feature of isolated complement C3 deposits in the glomerulus. A common aetiology involving dysregulation of the alternative pathway (AP) of complement has been elucidated in the past decade, with genetic defects and/or autoantibodies able to be identified in a proportion of patients. We review the clinical and histological features of C3 glomerulopathy, relating these to underlying molecular mechanisms. The role of uncontrolled C3 activation in pathogenesis is emphasized, with important lessons from animal models. Methods, advantages and limitations of gene testing in the assessment of individuals or families with C3 glomerulopathy are discussed. While no therapy has yet been shown consistently effective, clinical evaluation of agents targeting specific components of the complement system is ongoing. However, limits to current knowledge regarding the natural history and the appropriate timing and duration of proposed therapies need to be addressed.
Moschidou D, Sharp P, Behmoaras J, et al., 2013, Potential of human fetal chorionic stem cell therapy for Alport Syndrome, Conference of the British-Society-for-Gene-and-Cell-Therapy (BSGCT), Publisher: MARY ANN LIEBERT INC, Pages: A12-A12, ISSN: 1043-0342
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