Objective. High-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (HSCT) is a new treatment for patients with severe, refractory rheumatoid arthritis (RA). The present study was undertaken to assess the health status of patients with severe RA over a long-term followup period after treatment with HDC ؉ HSCT.Methods. Health status and utility scores were assessed in 8 patients before and after treatment with HDC ؉ HSCT. Patients were followed up for 5 years posttransplantation. Health status was assessed by the Health Assessment Questionnaire (HAQ), the RAND-36 version of the Short Form 36 (SF-36) health survey, and the Arthritis Impact Measurement Scales (AIMS). Utility scores were calculated using the EuroQol (EQ-5D) questionnaire and the SF-36-derived utility index (called the SF-6D), from which quality-adjusted life years (QALYs) were derived.Results. Most measures of health status improved compared with baseline in the first 2 years posttransplantation, notably HAQ and AIMS scores and scores on the functional status, general health, and health change summary scales of the RAND-36 version of the SF-36. Utility scores derived from the EQ-5D questionnaire and the SF-6D also increased significantly after transplantation. This was reflected in the 0.28 QALYs gained compared with baseline. For a putative 50-yearold RA patient with a life expectancy of 20 years, a threshold analysis revealed that HDC ؉ HSCT yielded more QALYs than conventional therapy when treatment-related mortality (TRM) was <2.8%.Conclusion. HDC ؉ HSCT temporarily increased the functionality and health status of patients with severe, refractory RA. With a reported TRM of 1.3%, HDC ؉ HSCT can be considered a realistic treatment option for patients with severe RA.
Recognising the clinical picture of SPES is relevant because surgical reconstruction of the chest can provide substantial relief of symptoms.
We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA). An indirect immunofluorescence test and rat oesophagus substrate was used for the detection and quantification of AKA antibodies in patients´ sera. Overall 33/60 patients with JIA had sera positive for AKA (55 %, P = 0,0001) ranging from 1:10 to 1:160 dilutions. Following idiopathic arthritis of childhood classification criteria AKA occurred in 2/7 patients with systemic disease (28,6 %), in 13/30 patients with RF negative polyarthritis (43,3 %, P = 0,008) and in 15/18 RF positive polyarthritis (83,3 %, P = 0,000002). AKA were also found in a small cohort of patients with oligoarthritis (1/3) and psoriatic arthritis (2/2). AKA positivity occurred in 3/26 healthy controls at a 1:20 dilution. The presence of AKA was correlated as well as with the severity of the disease. Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, however this did not reach statistical significance (P = 0,18). We also observed that AKA remained positive regardless of disease activity. AKA were detectable in 55,6 % patients with active JIA and in 48,6 % patients in the complete or near remission. Acknowledgement: This research was supported by a European Commission (Acronym: EUROBANK, contract no: QOL-2000-14.1), web site http://www.ncl.ac.uk and by grant of 2nd Medical Faculty, Charles University in Prague, VZ no. 111300003. P2The significance of antibodies to cyclic citrullinated peptide, antikeratin antibodies, antiperinuclear factor, rheumatoid factor isotypes and HLA shared epitope in prediction of erosive disease in early rheumatoid arthritis patients J Vencovsky, L Sedova, S Machacek, J Gatterova, V Pesakova, J Kafkova and O Krystufkova Institute of Rheumatology, Prague, Czech RepublicObjectives: To evaluate a predictive value of autoantibody examinations in development of erosive disease in early rheumatoid arthritis (RA). Patients and methods: One hundred and fourteen patients with disease duration less than 2 years after the onset of symptoms were investigated. Only patients who fulfilled the diagnostic criteria for RA either at the beginning of the disease or during the follow-up period were included. The antibodies to cyclic citrullinated peptide (anti-CCP) (Immunoscan RA, Euro-diagnostica, The Netherlands), IgM, IgA and IgG rheumatoid factors (RF) were measured by ELISA, antikeratin antibodies (AKA) and antiperinuclear factor (APF) were detected by indirect immunofluorescence, and the presence of HLA shared epitope (HLA SE) was detected by PCR with sequence specific primers. Patients were divided into two groups, either with erosive or non-erosive changes present on the hand or/and feet radiographs at the end of 24 months follow-up. Results: Seventy-six (66.7%) patients developed bony erosion, whereas 38 (33.3%) remained without destructive changes. The initial anti-CCP, AKA, APF, IgM RF, IgA RF, IgG RF ...
Chaperonins have classically been thought of as intracellular molecules involved in the correct folding of proteins. Their expression is upregulated during times of stress such as heat (hence their common nomenclature as heat shock proteins [HSP]), anoxia, hypoglycaemia and reactive oxygen species [1]. These are conditions found in infected tissues or in tissues with chronic inflammation such as the rheumatoid synovium. In their intracellular location they protect the cell from apoptotic death due to stress. Increasingly chaperonins have been recognised to subserve extracellular functions for which they have received the name 'chaperokines' since they bind to specific receptors on the cell surface and activate cells of the innate immune system to secrete inflammatory cytokines, chemokines and small molecular weight mediators such as prostaglandins [2]. Indeed, an early event in inflammation is cell stress/necrosis leading to the release of HSP60 and HSP70 that binds via a CD14-mediated mechanism to Toll-like receptors 2 and 4 [2] as part of the 'danger' signal [3]. The secretion of tumour necrosis factor alpha, IL-1, IL-12 and other chemokines prepares the environment for a TH1 adaptive immune response. It is now recognised that some chaperonins, such as BiP and HSP27, may activate the innate immune system to secrete anti-inflammatory cytokines, such as IL-10 [4,5] that may skew the adaptive immune response to TH2. Recent work by our group has shown that BiP can not only prevent but also treat ongoing collagen-induced arthritis in DBA/1 mice [6], suggesting that chaperonins may down modulate ongoing TH1 responses. Thus, it may be possible to suppress rheumatoid inflammation by administration of appropriate chaperonins such as BiP. Finally, chaperonins may be important system regulators determining the outcome between TH1 and Th2 immune responses. References 1. Pockley AG: Heat shock proteins as regulators of the immune response. Lancet 2003, 362:469-476. 2. Asea A: Chaperokine-induced signal transduction pathways. Exerc Immunol Rev 2003, 9:25-33. 3. Matzinger P: The danger model: a renewed sense of self. Science 2002, 296:301-305. 4. De AK, Kodys KM, Yeh BS, Miller-Graziano C: Exaggerated human monocyte IL-10 concomitant to minimal TNF-alpha induction by heatshock protein 27 (Hsp27) suggests Hsp27 is primarily an antiinflammatory stimulus.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.