Search

Your search keyword '"Cambridge, Geraldine"' showing total 191 results
Start Over Author "Cambridge, Geraldine"
191 results on '"Cambridge, Geraldine"'

4. Naturally acquired adaptive immunity to Streptococcus pneumoniae is impaired in rheumatoid arthritis patients.

Author

Ercoli, Giuseppe, Selway‐Clarke, Hugh, Truijen, Dena, Folkmanaite, Milda, Oulton, Tate, Norris‐Grey, Caitlin, Nakajima, Rie, Felgner, Philip, Wren, Brendan W, Tetteh, Kevin, Croucher, Nicholas J, Leandro, Maria, Cambridge, Geraldine, and Brown, Jeremy S

Abstract

Objectives: Patients with rheumatoid arthritis (RA) have an increased susceptibility to infections, including those caused by Streptococcus pneumoniae. Why RA is associated with increased susceptibility to S. pneumoniae is poorly understood. This study aims to assess the effects of RA and B‐cell depletion therapy on naturally acquired antibody responses to 289 S. pneumoniae protein antigens using a novel protein array. Methods: IgG responses to S. pneumoniae were characterised in serum from RA patients and disease controls (myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)) using whole‐cell ELISA, a flow cytometry opsonisation assay and an S. pneumoniae protein array. For the RA patients, results were compared before and after B‐cell depletion therapy. Results: Compared to a well‐characterised disease control group of ME/CFS patients, RA patients had reduced antibody responses to multiple S. pneumoniae protein antigens, with significant IgG recognition of approximately half the number of antigens along with reduced median strengths of these responses. Reduction in multiple array antigen‐specific responses also correlated with reduced IgG opsonisation of S. pneumoniae. Although B‐cell depletion therapy with rituximab did not reduce overall IgG recognition of S. pneumoniae in the RA group, it was associated with marked disruption of pre‐existing IgG repertoire to protein antigens in individual patients. Conclusion: These data show RA is associated with major disruption of naturally acquired adaptive immunity to S. pneumoniae, which can be assessed rapidly using a protein antigen array and is likely to contribute towards the increased incidence of pneumonia in patients with RA. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

7. Naturally acquired adaptive immunity to Streptococcus pneumoniae is impaired in rheumatoid arthritis patients

Author

Ercoli, Giuseppe, primary, Selway, Hugh, additional, Folkmanaite, Milda, additional, Oulton, Tate, additional, Norris-Grey, Caitlin, additional, Nakajima, Rie, additional, Felgner, Philip, additional, Wren, Brendan W., additional, Tetteh, Kevin, additional, Leandro, Maria, additional, Cambridge, Geraldine, additional, and Brown, Jeremy S., additional

Published
2023
Full Text
View/download PDF

12. Disparity in peripheral and renal B-cell depletion with rituximab in systemic lupus erythematosus: an opportunity for obinutuzumab?

Author

Reddy, Venkat R, primary, Pepper, Ruth J, additional, Shah, Kavina, additional, Cambridge, Geraldine, additional, Henderson, Scott R, additional, Klein, Christian, additional, Kell, Loren, additional, Taylor, Samuel J, additional, Isenberg, David A, additional, Cragg, Mark S, additional, and Leandro, Maria J, additional

Published
2021
Full Text
View/download PDF

14. Disparity in peripheral and renal B-cell depletion with rituximab in systemic lupus erythematosus: an opportunity for obinutuzumab?

Author

Reddy, Venkat R, Pepper, Ruth J, Shah, Kavina, Cambridge, Geraldine, Henderson, Scott R, Klein, Christian, Kell, Loren, Taylor, Samuel J, Isenberg, David A, Cragg, Mark S, and Leandro, Maria J

Subjects
RITUXIMAB, IN vitro studies, B cells, BIOPSY, KIDNEYS, MONOCLONAL antibodies, RHEUMATOID arthritis, DISEASE duration, SYSTEMIC lupus erythematosus
Abstract

Objectives To investigate key factors that may contribute to the variability of rituximab-mediated peripheral and renal B cell depletion (BCD) in SLE. Methods We analysed: (i) CD19+ B cell counts in patients with SLE before and 1, 2, 3 and 6 months after treatment with rituximab, comparing them with RA patients; (ii) the presence of B cells in renal biopsies after rituximab therapy; (iii) whether the duration of BCD correlated with patient demographics and B cell expression of CD20 and FcγRIIb; and (iv) the effect of B cell activation factor (BAFF) on the efficiency of rituximab and obinutuzumab at inducing BCD in whole blood assays, in vitro. Results In SLE (n  = 71), the duration of BCD was shorter compared with RA (n  = 27). B cells were detectable in renal biopsy samples (n  = 6) after treatment with rituximab in all patients with poor response while peripheral blood B cells remained low or undetectable in the same patients. There were no significant relationships between peripheral BCD and patient age, disease duration, serum C3 levels or the level of expression of B cell surface proteins CD20 and FcγRIIb. Obinutuzumab was more efficient than rituximab at inducing BCD in whole blood assays, regardless of excess BAFF. Conclusions BCD in SLE is less efficient than in RA. Renal B cell presence following rituximab treatment was associated with poor outcomes. No significant relationships between any measured B cell related, clinical or laboratory parameters and the efficiency of BCD by rituximab was found. Obinutuzumab was superior to rituximab at inducing BCD. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

24. Studies on the immunopathology of inflammatory muscle disease

Author

Cambridge, Geraldine

Subjects
616.7
Abstract

Inflammatory muscle disease is a rare condition which includes polymyositis and dermatomyositis. Although its aetiology is unknown, its pathogenesis, which results in damage to muscle fibres, is thought to have a lymphocyte mediated basis. Research into this desease has been handicapped by the lack of suitable in vitro correlate of immunologically mediated muscle cell damage. These studies set out to establish an in vitro myotoxicit.y assay based on the culture of human fetal skeletal muscle and a radiolabel specific for myotubes (pre-muscle cells), tritium-labelled carnitine. Initially, the kinetics of carnitine transport across myotube membranes was studied in the mixed cell cultures derived from disaggregated muscle tissue. As these experiments proceeded, research was designed to examine the correlation between clinically determined disease.activity and j[n vitro measurement of myo-toxicity by peripheral blood lymphocytes from affected individuals, and the value of these tests in ‘distinguishing disease groups. Investigation of the movement of tritium-labelled carnitine across muscle cell membranes in human fetal muscle cultures, showed that carnitine was taken up by myotubes by an active transport mechanism. The parameters of this system were established, including the Kn and Vmax of the enzymes involved. The specificity of carnitine uptake by myotubes was also demonstrated by freeze-dried autoradiography. Using human fetal skeletal muscle cultures labelled with carnitine in short term cytotoxicity assays, it was shown that peripheral blood lymphocytes from patients with polymyositis specifically damaged myotubes and that this cytoyoxic ability correlated with clinical activity of the disease. The occasional finding of myotoxicity by lymphocytes from normal individuals, led to the demonstration that a significant proportion of the cytotoxicity was mediated by Spontaneous or Natural Killer cells. Consequent measurement of Natural Killer cell activity in patients with polymyositis revealed that some specificity for muscle cell targets was evident in peripheral blood lymphocyte populaions from polymyositis patients, but not in those from normal individuals. The clinically based experiments showed that lymphocytes from patients with polymyositis have some specificity in their j_n vitro cytotoxic responses for muscle cell antigens. The results of this thesis suggest the direction, and provide some of the methods for further investigations into the pathogenesis of inflammatory muscle disease.

Published
1985

26. Long-term persistence of rituximab in patients with rheumatoid arthritis: an evaluation of the UCL cohort from 1998 to 2020.

Author

Norris-Grey, Caitlin, Cambridge, Geraldine, Moore, Samantha, Reddy, Venkat, and Leandro, Maria

Subjects
*RITUXIMAB, *AUTOANTIBODIES, *ACADEMIC medical centers, *ACQUISITION of data methodology, *AGE distribution, *LOG-rank test, *TREATMENT duration, *RETROSPECTIVE studies, *RISK assessment, *SEX distribution, *ANTIRHEUMATIC agents, *TREATMENT failure, *RHEUMATOID arthritis, *MEDICAL records, *DISEASE duration, *KAPLAN-Meier estimator, *DESCRIPTIVE statistics, *TERMINATION of treatment, *LONGITUDINAL method, *PROPORTIONAL hazards models
Abstract

Objectives B cell depletion therapy based on rituximab in patients with RA was pioneered at University College London Hospitals/University College London in 1998. The objective of this study was to evaluate long-term persistence of rituximab and identify factors associated with discontinuation of treatment. Methods Retrospective review of medical records from all rituximab-treated RA patients followed up in a dedicated clinic (1998–2020). Data collected included gender, disease duration, previous DMARDs, autoantibody status, age and concomitant therapy at first cycle, length of follow-up, and number of cycles. Drug survival and factors associated with drug discontinuation were analysed using Kaplan–Meier survival curves, log-rank test and Cox regression analysis. Results A total of 404 patients were included. Median disease duration and age at time of first rituximab cycle were 10 and 57 years, respectively. Median total follow-up was 55 months and median number of cycles five. 93.1% of patients were seropositive. Overall, 31.2% of patients stopped rituximab, with the largest reason for discontinuing being primary inefficacy (42.1%). Comparison of Kaplan–Meier curves showed that rituximab drug survival was lower in seronegative patients and in patients who had previously failed at least one biologic DMARD (bDMARD). Cox regression analysis revealed that rituximab discontinuation was associated with a greater number of previous bDMARDs. Conclusion Many patients with RA achieve good control of their disease with repeated cycles of rituximab treatment. The most common reasons for treatment discontinuation were either primary or secondary inefficacy. Patients who were seronegative and who had previously failed other bDMARDs were more at risk of drug discontinuation. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

36. CD24 Expression and B Cell Maturation Shows a Novel Link With Energy Metabolism: Potential Implications for Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Author

Mensah, Fane F. K., Armstrong, Christopher W., Reddy, Venkat, Bansal, Amolak S., Berkovitz, Saul, Leandro, Maria J., and Cambridge, Geraldine

Subjects
lcsh:Immunologic diseases. Allergy, B cells, Immunology, memory B cells, Immunology and Allergy, pAMPK, skin and connective tissue diseases, lcsh:RC581-607, CD24, metabolism, ME/CFS
Abstract

CD24 expression on pro-B cells plays a role in B cell selection and development in the bone marrow. We previously detected higher CD24 expression and frequency within IgD+ naïve and memory B cells in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) compared with age-matched healthy controls (HC). Here, we investigated the relationship between CD24 expression and B cell maturation. In vitro stimulation of isolated B cells in response to conventional agonists were used to follow the dynamics of CD24 positivity during proliferation and differentiation (or maturation). The relationship between CD24 expression to cycles of proliferation and metabolism in purified B cells from HC was also investigated using phospho-flow (phosphorylation of AMPK-pAMPK), 1proton nuclear magnetic resonance and Mitotracker Far-red (Mitochondrial mass-MM). In vitro, in the absence of stimulation, there was an increased percentage of CD24+ viable B cells in ME/CFS patients compared to HC (p < 0.05) following 5 days culture. Following stimulation with B cell agonists, percentage of CD24+B cells in both naïve and memory B cell populations decreased. P < 0.01). There was a negative relationship between percentage of CD24+B cells with MM (R2 = 0.76; p < 0.01), which was subsequently lost over sequential cycles of proliferation. There was a significant correlation between CD24 expression on B cells and the usage of glucose and secretion of lactate in vitro. Short term ligation of the B cell receptor with anti-IgM antibody significantly reduced the viability of CD24+ memory B cells compared to those cross-linked by anti-IgD or anti-IgG antibody. A clear difference was found between naïve and memory B cells with respect to CD24 expression and pAMPK, most notably a strong positive association in IgD+IgM+ memory B cells. In vitro findings confirmed dysregulation of CD24-expressing B cells from ME/CFS patients previously suggested by immunophenotype studies of B cells from peripheral blood. CD24-negative B cells underwent productive proliferation whereas CD24+ B cells were either unresponsive or susceptible to cell death upon BCR-engagement alone. We suggest that CD24 expression may reflect variations in energy metabolism on different B cell subsets.

Published
2018

38. Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Author

Mehta, Puja, Holder, Susan, Fisher, Benjamin, Vincent, Tonia, Nadesalingam, Kavitha, Maciver, Helen, Shingler, Wendy, Bakshi, Jyoti, Hassan, Sadon, D'Cruz, David, Chan, Antoni, Litwic, Anna E., McCrae, Fiona, Seth, Rakhi, Nandagudi, Anupama, Jury, Elizabeth, Isenberg, David, Karjigi, Uma, Paul, Anupam, Rees, Frances, O'Dowd, Emma, Kinnear, William, Johnson, Simon, Lanyon, Peter, Stevens, Richard, Narayan, Nehal, Marguerie, Christopher, Robinson, Helena, Ffolkes, Lorrette, Worsnop, Fiona, Ostlere, Lucy, Kiely, Patrick, Dharmapalaiah, Chethana, Hassan, Nada, Bharadwaj, Anurag, Skibinska, Malgorzata, Gendi, Nagui, Davies, Emma J., Akil, Mohammed, Kilding, Rachael, Ramachandran Nair, Jagdish, Walsh, Maeve, Farrar, Wendy, Thompson, Robert N., Borukhson, Liubov, McFadyen, Charles, Singh, Deepwant, Rajagopal, Vivek, Chan, Angela Marie L., Wearn Koh, Li, Christie, Jennifer D., Croot, Lorraine, Gayed, Mary, Disney, Benjamin, Singhal, Saket, Grindulis, Karl, Reynolds, Timothy D., Conway, Katie, Williams, Debbie, Quin, John, Dean, Gillian, Churchill, Duncan, Walker-Bone, Karen E., Goff, Iain, Reynolds, Gary, Grove, Matthew, Patel, Priya, Lazarus, Mark N., Roncaroli, Frederico, Gabriel, Carolyn, Kinderlerer, Anne R., Nikiphorou, Elena, Hall, Frances C., Bruce, Ellen, Gray, Leanne, Krutikov, Maria, Wig, Surabhi, Bruce, Ian, D'Agostino, Maria A., Wakefield, Richard, Berner Hammer, Hilde, Vittecoq, Olivier, Galeazzi, Mauro, Balint, Peter, Filippucci, Emilio, Moller, Ingrid, Iagnocco, Annamaria, Naredo, Esperanza, Ostergaard, Mikkel, Gaillez, Corine, Kerselaers, Wendy, Van Holder, Karina, Le Bars, Manuela, Stone, Millicent A., Williams, Francis, Wolber, Lisa, Karppinen, Jaro, Maatta, Juhani, Thompson, Ben, Atchia, Ismael, Lorenzi, Alice, Raftery, Graham, Platt, Phil, Platt, Philip N., Pratt, Arthur, Turmezei, Thomas D., Treece, Graham M., Gee, Andrew H., Poole, Kenneth E., Chandratre, Priyanka N., Roddy, Edward, Clarson, Lorna, Richardson, Jane, Hider, Samantha, Mallen, Christian, Lieberman, Abigail, Prouse, Peter J., Mahendran, Prini, Samarawickrama, Amanda, Ottery, Faith D., Yood, Robert, Wolfson, Marsha, Ang, Andrea, Riches, Philip, Thomson, Janet, Nuki, George, Humphreys, Jennifer, Verstappen, Suzanne M., Chipping, Jacqueline, Hyrich, Kimme, Marshall, Tarnya, Symmons, Deborah P., Roy, Matthew, Kirwan, John R., Marshall, Robert W., Matcham, Faith, Scott, Ian C., Rayner, Lauren, Hotopf, Matthew, Kingsley, Gabrielle H., Scott, David L., Steer, Sophia, Ma, Margaret H., Dahanayake, Chanaka, Kingsley, Gabrielle, Cope, Andrew, Wernham, Aaron, Ward, Lorna, Carruthers, David, Deeming, Alison, Buckley, Christopher, Raza, Karim, De Pablo, Paola, Carpenter, Lewis, Jayakumar, Keeranur, Solymossy, Csilla, Dixey, Josh, Young, Adam, Singh, Animesh, Penn, Henry, Ellerby, Nicholas, Mattey, Derek L., Packham, Jonathan, Dawes, Peter, Hider, Samantha L., Ng, Nora, Humby, Frances, Bombardieri, Michele, Kelly, Stephen, Di Cicco, Maria, Dadoun, Sabrina, Hands, Rebecca, Rocher, Vidalba, Kidd, Bruce, Pyne, Dev, Pitzalis, Costantino, Poore, Sophie, Hutchinson, David, Low, Audrey, Lunt, Mark, Mercer, Louise, Galloway, James, Davies, Rebecca, Watson, Kath, Dixon, Will, Symmons, Deborah, Watson, Kath D., Dixon, William G., Hyrich, Kimme L., Malik, Saadia P., Kelly, Clive, Hamilton, Jennifer, Heycock, Carol, Saravanan, Vadivelu, Rynne, Martin, Harris, Helen E., Tweedie, Fiona, Skaparis, Yiannis, White, Marie, Scott, Nicola, Samson, Kay, Mercieca, Cecilia, Clarke, Shane, Warner, Alexander J., Verstappen, Suzanne, Chan, Esther, Woodhead, Felix A., Nisar, Mohamed, Arthanari, S., Dawson, Julie, Sathi, Nav, Ahmad, Yasmeen, Koduri, Gouri, Cumming, Jo, Stannett, Peter, Hull, Richard, Metsios, George, Stavropoulos Kalinoglou, Antonios, Veldhuijzen van Zanten, Jet J., Nightingale, Peter, Koutedakis, Yiannis, Kitas, George D., Williams, Peter, Walsh, David, Perry, Elizabeth, de-Soyza, Anthony, Moullaali, Thomas, Eggleton, Paul, Stavropoulos-Kalinoglou, Antonios, Sandoo, Aamer, de Pablo, Paola, Maggs, Fiona, Faizal, Abdul, Pugh, Mark, Jobanputra, Paresh, Kehoe, Oksana, Cartwright, Alison, Askari, Ayman, El Haj, Alicia, Middleton, Jim, Aynsley, Sarah, Hardy, Jacob, Veale, Douglas, Fearon, Ursula, Wilson, Gerry, Muthana, Munitta, Fossati, G., Healy, L., Nesbitt, A., Becerra, Elena, Leandro, Maria J., De La Torre, Inmaculada, Cambridge, Geraldine, Nelson, P. N., Roden, D., Shaw, M., Davari Ejtehadi, Hora, Nevill, A., Freimanis, G., Hooley, P., Bowman, S., Alavi, A., Axford, J., Veitch, A. M., Tugnet, N., Rylance, P. B., Hawtree, Sarah, Mark Wilkinson, J., Wilson, Anthony G., Woon Kam, Ngar, Filter, Andrew, Croft, Adam P., Naylor, Amy, Zimmermann, Birgit, Hardie, Debbie, Desanti, Guillaume, Jaurez, Maria, Muller-Ladner, Ulf, Filer, Andrew, Neumann, Elena, Movahedi, Mohammad, Ray, David W., Burmester, Gerd R., Matucci-Cerinic, Marco, Navarro-Blasco, Francisco, Kary, Sonja, Unnebrink, Kristina, Kupper, Hartmut, Mukherjee, Sandeep, Cornell, Patricia, Richards, Selwyn, Rahmeh, Fouz, Thompson, Paul W., Westlake, Sarah L., Javaid, Muhammad K., Batra, Rajbir, Chana, Jasroop, Round, Gemma, Judge, Andrew, Taylor, Peter, Patel, Sanjeev, Cooper, Cyrus, Ravindran, Vinod, Bingham, Clifton O., Weinblatt, Michael E., Mendelsohn, Alan, Kim, Lilianne, Mack, Michael, Lu, Jiandong, Baker, Daniel, Westhovens, Rene, Hewitt, Jamie, Han, Chenglong, Keystone, Edward C., Fleischmann, Roy, Smolen, Josef, Emery, Paul, Genovese, Mark, Doyle, Mittie, Hsia, Elizabeth C., Hart, Jennifer C., Harland, Dave, Gibbons, Carl, Pang, Hok, Huertas, Catherine, Diamantopoulos, Alex, Dejonckheere, Fred, Clowse, M., Wolf, D., Stach, C., Kosutic, G., Williams, S., Terpstra, I., Mahadevan, U., Ferraccioli, G., Samborski, W., Berenbaum, F., Davies, O., Koetse, W., Bennett, B., Burkhardt, H., Luijtens, K., van der Heijde, Desiree, Mariette, X., van Vollenhoven, Ronald F., Bykerk, V., de Longueville, M., Arendt, C., Cush, J., Khan, Afsha, Maclaren, Zoe, Dubash, Sayam, Chalam, Venkat C., Sheeran, Tom, Price, Tom, Baskar, Sangeetha, Mulherin, Diarmuid, Molloy, Cauline, Keay, Fiona, Heritage, Caroline, Douglas, Barbara, Schiff, Michael H., Khanna, Dinesh, Furst, Daniel E., Maldonado, Michael A., Li, Wanying, Sasso, Eric H., Emerling, Daniel, Cavet, Guy, Ford, Kerri, Mackenzie-Green, Bronwen, Collins, David, Price, Elizabeth, Williamson, Lyn, Golla, Janardhana, Vagadia, Vipul, Morrison, Elaine, Tierney, Ann, Wilson, Hilary, Hunter, John, Reddy, Venkat, Moore, Samantha, Ehrenstein, Michael, Benson, Claire, Wray, Maria, Cairns, Andrew, Wright, Gary, Pendleton, Adrian, McHenry, Michelle, Taggart, Allister, Bell, Aubrey, Bosworth, Ailsa, Cox, Maureen, Johnston, Graeme, Shah, Preeti, O'Brien, Anne, Jones, Peter, Sargeant, Ify, Bukhari, Marwan, Nusslein, Hubert, Alten, Rieke, Lorenz, Hannes M., Boumpas, Dimitrios, Nurmohamed, Michael T., Bensen, William, Peter, Hans-Hartmut, Rainer, Franz, Pavelka, Karel, Chartier, Melanie, Poncet, Coralie, Rauch, Christiane, Lempp, Heidi, Hofmann, Darija, Adu, Aderonke, Congreve, Carron, Dobson, Joanne, Rose, Diana, Simpson, Carol, Wykes, Til, Ibrahim, Fowzia, Schiff, Michael, Nash, Peter, Durez, Patrick, Kaine, Jeffrey, Delaet, Ingrid, Kelly, Sheila, Maldonado, Michael, Patel, Salil, Jones, Graeme, Sebba, Anthony, Lepley, Denise, Devenport, Jenny, Bernasconi, Corrado, Smart, Devi, Mpofu, Chiedzo, Gomez-Reino, Juan J., Verma, Inderjeet, Kaur, Jaspreet, Syngle, Ashit, Krishan, Pawan, Vohra, Kanchan, Kaur, Ladbans, Garg, Nidhi, Chhabara, Monica, Gibson, Kellie, Woodburn, James, Telfer, Scott, Buckley, Felicity, Finckh, Axel, Huizinga, Tom W., Jansen, Jeroen P., Rubbert-Roth, Andrea, Scali, Juan J., Kremer, Joel M., Pitts, Laura, Vernon, Emma, Sharif, Mohammed I., Das, Sudipto, Helliwell, Philip, Sokoll, Katharina, and Vital, Edward M.

Subjects
cardiovascular system
Abstract

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interest

Published
2017

39. Rheumatoid arthritis - clinical aspects: 134. Predictors of Joint Damage in South Africans with Rheumatoid Arthritis

Author

Ickinger, Claudia, Musenge, Eustasius, Tikly, Mohammed, Barnes, Jonathan, Donnison, C., Scott, M., Bartholomew, Peter, Rynne, Martin, Hamilton, Jennifer, Saravanan, V., Heycock, Carol, Kelly, Clive, de la Torre, Inmaculada, Moura, Rita A., Leandro, Maria, Edwards, Jonathan, Cambridge, Geraldine, Edwards, Johnathan, Daniels, Louise E., Gullick, Nicola J., Rees, Jonathan D., Kirkham, Bruce W., Rees, Jonathan, Scott, Ian C., Johnson, Deborah, Scott, David L., Kingsley, Gabrielle, Ma, Margaret H., Cope, Andrew P., Brode, Sven, Nisar, Muhammad K., Östör, Andrew J., Oakley, Stephen P., Jones, Tim, Mistlin, Alan, Panayi, Gabriel S., El Miedany, Yasser, Palmer, Deborah, Porkodi, Ramanathan, Rajendran, Panchapakesa, Waller, Rosemary, Williamson, Lyn, Collins, David, Price, Elizabeth, Juarez, Maria J., El Gaafary, Maha, Youssef, sally, Cramp, Fiona, Hewlett, Sarah, Almeida, Celia, Kirwan, John, Choy, Ernest, Chalder, Trudie, Pollock, Jon, Christensen, Robin, Mirjafari, Hoda, Verstappen, Suzanne, Bunn, Diane, Edlin, Helena, Charlton-Menys, Valentine, Pemberton, Philip, Marshall, Tarnya, Wilson, Paddy, Lunt, Mark, Symmons, Deborah, Bruce, Ian N., Bell, Carolyn, Rowe, Ian F., Jayakumar, Keeranur, Norton, Sam J., Dixey, Josh, Williams, Peter, Young, Adam, Kurunadalingam, Hariney, Parwaiz, Iram, Kumar, Kanta, Howlett, Kath, Hands, Becki, Raza, Karim, Pitzalis, Costantino, Buckley, Chris, Kelly, Stephen, Filer, Andrew, Wheater, Gill, Hogan, Vanessa E., Onno Teng, YK, Tekstra, Janneke, Tuck, Stephen P., Lafeber, Floris P., Huizinga, Tom W., Bijlsma, Johannes W., Francis, Roger M., Datta, Harish K., van Laar, Jaap, Pratt, Arthur G., Charles, Peter J., Choudhury, Muslima, Wilson, Gill, Venables, Patrick J., Isaacs, John, Stack, Rebecca, Kwiatkowska, Brygida, Rantapaa-Dahlqvist, Solbritt, Saxne, Tore, Sidiropoulos, Prodromos, Kteniadaki, Eleni, Misirlaki, Chariklia, Mann, Herman, Vencovsky, Jiri, Ciurea, Adrian, Tamborrini, Giorgio, Kyburz, Diego, Bastian, Hans, Burmester, Gerd R., Detert, Jacqueline, Buckley, Christopher D., Sheehy, Claire, Shipman, Alexa, Stech, Irina, Mukhtyar, Chetan, Atzeni, Fabiola, Sitia, Simona, Tomasoni, Livio, Gianturco, Luigi, Ricci, Cristian, Sarzi-Puttini, Piercarlo, De Gennaro Colonna, Vito, Turiel, Maurizio, Galloway, James, Low, Audrey, Mercer, Louise K., Dixon, Will, Ustianowski, Andrew, Watson, Kath, Fisher, Benjamin, Plant, Darren, Lundberg, Karin, Barton, Anne, Venables, Patrick, Lorenzi, Alice R., and Platt, Philip N.

Abstract

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA. Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value

Published
2017

40. Obinutuzumab induces superior B-Cell cytotoxicity to rituximab in rheumatoid arthritis and systemic lupus erythematosus patient samples

Author

Reddy, Venkat, Klein, Christian, Isenberg, David, Glennie, Martin, Cambridge, Geraldine, Cragg, Mark, and Leandro, Maria

Subjects
immune system diseases
Abstract

Objective A proportion of Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) patients treated with standard doses of rituximab (RTX) display inefficient B cell deletion and poor clinical responses which can be augmented by delivering higher doses, indicating that standard-dose RTX is a sub-optimal therapy in these patients. To investigate whether better responses could be achieved with mechanistically different anti-CD20 mAbs.Methods We compared RTX with Obinutuzumab (OBZ), a new-generation, glycoengineered type II anti-CD20 mAb in a series of in vitro assays measuring B cell cytotoxicity in RA and SLE patient samples.Results We found that OBZ was at least 2-fold more efficient than RTX at inducing B-cell cytotoxicity in in-vitro whole blood assays. Dissecting this difference, we found that RTX elicited more potent complement-dependent cellular cytotoxicity (CDC) than OBZ. In contrast, OBZ was more effective at evoking Fc gamma receptor (FcγR)-mediated effector mechanisms, including activation of NK cells and neutrophils, probably due to stronger interaction with FcγRs and the ability of OBZ to remain at the cell surface following CD20 engagement, whereas RTX became internalized. OBZ was also more efficient at inducing direct cell death. This was true for all CD19+ B-cells as a whole and in naïve (IgD+CD27-); and switched (IgD-CD27+) memory B-cells specifically, a higher frequency of which is associated with poor clinical response after RTX.Conclusions Taken together, these data provide a mechanistic basis for resistance to Rituximab induced B-cell depletion, and for considering Obinutuzumab, as an alternative B-cell depleting agent in RA and SLE.

Published
2017

41. Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long-Term Effects on Serum Immunoglobulins

Author

Reddy, Venkat, Martinez, Lina, Isenberg, David A, Leandro, Maria J, and Cambridge, Geraldine

Subjects
Adult, Male, Time Factors, Adolescent, Middle Aged, Young Adult, Cross-Sectional Studies, Treatment Outcome, Immunoglobulin M, immune system diseases, Antirheumatic Agents, Humans, Lupus Erythematosus, Systemic, Female, skin and connective tissue diseases, Rituximab, Biomarkers, Aged, Follow-Up Studies
Abstract

B cell-depletion therapy based on rituximab is a therapeutic option for refractory disease in patients with systemic lupus erythematosus (SLE). The aim of this observational study was to document long-term effects on B cell function by following serum immunoglobulin levels in patients with SLE treated with rituximab in routine clinical practice.

Published
2017

42. Detection of Experimental and Clinical Immune Complexes by Measuring SHIP-1 Recruitment to the Inhibitory FcγRIIB

Author

Stopforth, Richard J., primary, Oldham, Robert J., additional, Tutt, Alison L., additional, Duriez, Patrick, additional, Chan, H. T. Claude, additional, Binkowski, Brock F., additional, Zimprich, Chad, additional, Li, Dun, additional, Hargreaves, Philip G., additional, Cong, Mei, additional, Reddy, Venkat, additional, Leandro, Maria J., additional, Cambridge, Geraldine, additional, Lux, Anja, additional, Nimmerjahn, Falk, additional, and Cragg, Mark S., additional

Published
2018
Full Text
View/download PDF

48. Expression of the inherently autoreactive idiotope 9G4 on autoantibodies to citrullinated peptides and on rheumatoid factors in patients with early and established rheumatoid arthritis

Author

Cambridge, Geraldine, Moura, Rita, Santos, Tania, Khawaja, Akif A., Polido Pereira, Joaquim, Canhao, Helena, Leandro, Maria J., Fonseca, João Eurico, and Repositório da Universidade de Lisboa

Subjects
Adult, Male, General Science & Technology, lcsh:Medicine, Peptides, Cyclic, MATURATION, B-CELL SUBPOPULATIONS, V(H)4-21 GENE, Arthritis, Rheumatoid, Epitopes, Immunoglobulin Idiotypes, Rheumatoid Factor, Animals, Humans, USAGE, lcsh:Science, Aged, B-Lymphocytes, Science & Technology, IGM, lcsh:R, SEGMENT, Antibodies, Monoclonal, Middle Aged, Rats, Multidisciplinary Sciences, ANTIBODIES, Science & Technology - Other Topics, lcsh:Q, Female, REFLECTS
Abstract

Copyright: © 2014 Cambridge et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., Background: The pre-symptomatic stage of Rheumatoid arthritis (RA) is associated with pro-inflammatory cytokines and autoantibodies. High levels and epitope spread by Rheumatoid factors (RhF) and autoantibodies to citrullinated proteins signify progression towards disease expression. In established RA, the persistence of high autoantibody levels reflects production by both long-lived plasma cells and short-lived plasmablasts. Neither the relative contributions to pathogenesis by autoantibodies from either source, nor the factors responsible for deciding the fate of autoantigen specific 'parent' B-cells, is understood. Phenotypic markers identifying subsets of autoreactive B-cells are therefore of interest in understanding the origin and perpetuation of the autoimmune response in RA. One such phenotypic marker is the rat monoclonal antibody, 9G4, which recognises an idiotope on immunoglobuins derived from the inherently autoreactive VH-gene, VH4-34. We therefore investigated whether the 9G4 idiotope was expressed on autoantibodies in patients with RA. Methodology/principal findings: Sera from 19 patients with established RA and those with, RAM was supported with a fellowship from Fundação para a Ciência e a Tecnologia (FCT, SFRH/BPD/81936/2011). TS was supported with a grant from Erasmus Programme.

Published
2014

Catalog

Books, media, physical & digital resources
See catalog results