SAT0201 Induction therapy with short-term high dose intravenous cyclophosphamide followed by mycophenolate mofetil in patients with proliferative lupus nephritis
Abstract:Background
For decades, high dose intravenous cyclophosphamide (ivCY) given for 24-30 months was regarded as standard therapy for proliferative lupus nephritis (LN), despite serious side effects.(1)
Objectives
To evaluate the effect of induction therapy with short-term high dose ivCY followed by mycophenolate mofetil (MMF) on renal function and mortality in patients with proliferative LN.
Methods
Between January 2003 and November 2006, 74 patients with biopsy-proven proliferative LN were included in the seco… Show more
“… Figure 2 Health-related quality of life using the SF-36 in patients with SLE and NP symptoms, compared with patients with other (chronic) diseases in the Dutch population. 20 – 24 PF: physical functioning; RP: role functioning, physical; BP: bodily pain; GH: general health; V: vitality; SF: social functioning; RE: role functioning, emotional; MH: mental health; NPSLE: neuropsychiatric systemic lupus erythematosus; RA: rheumatoid arthritis; SF-36: Short-Form Health Survey …”
Section: Resultsmentioning
confidence: 99%
“…The QoL of the patients in the NPSLE cohort was measured during the first visit and a comparison in QoL was made with data available from the general Dutch population 20 , 21 and other cohorts of Dutch patients with chronic diseases: migraine, 20 mood disorder, 22 RA 23 and lupus nephritis. 24 …”
ObjectiveAssess quality of life in patients with systemic lupus erythematosus (SLE) presenting with neuropsychiatric symptoms (neuropsychiatric SLE, NPSLE).MethodsQuality of life was assessed using the Short-Form 36 item Health Survey (SF-36) in patients visiting the Leiden NPSLE clinic at baseline and at follow-up. SF-36 subscales and summary scores were calculated and compared with quality of life of the general Dutch population and patients with other chronic diseases.ResultsAt baseline, quality of life was assessed in 248 SLE patients, of whom 98 had NPSLE (39.7%). Follow-up data were available for 104 patients (42%), of whom 64 had NPSLE (61.5%). SLE patients presenting neuropsychiatric symptoms showed a significantly reduced quality of life in all subscales of the SF-36. Quality of life at follow-up showed a significant improvement in physical functioning role (p = 0.001), social functioning (p = 0.007), vitality (p = 0.023), mental health (p = 0.014) and mental component score (p = 0.042) in patients with neuropsychiatric symptoms not attributed to SLE, but no significant improvement was seen in patients with NPSLE.ConclusionQuality of life is significantly reduced in patients with SLE presenting neuropsychiatric symptoms compared with the general population and patients with other chronic diseases. Quality of life remains considerably impaired at follow-up. Our results illustrate the need for biopsychosocial care in patients with SLE and neuropsychiatric symptoms.
“… Figure 2 Health-related quality of life using the SF-36 in patients with SLE and NP symptoms, compared with patients with other (chronic) diseases in the Dutch population. 20 – 24 PF: physical functioning; RP: role functioning, physical; BP: bodily pain; GH: general health; V: vitality; SF: social functioning; RE: role functioning, emotional; MH: mental health; NPSLE: neuropsychiatric systemic lupus erythematosus; RA: rheumatoid arthritis; SF-36: Short-Form Health Survey …”
Section: Resultsmentioning
confidence: 99%
“…The QoL of the patients in the NPSLE cohort was measured during the first visit and a comparison in QoL was made with data available from the general Dutch population 20 , 21 and other cohorts of Dutch patients with chronic diseases: migraine, 20 mood disorder, 22 RA 23 and lupus nephritis. 24 …”
ObjectiveAssess quality of life in patients with systemic lupus erythematosus (SLE) presenting with neuropsychiatric symptoms (neuropsychiatric SLE, NPSLE).MethodsQuality of life was assessed using the Short-Form 36 item Health Survey (SF-36) in patients visiting the Leiden NPSLE clinic at baseline and at follow-up. SF-36 subscales and summary scores were calculated and compared with quality of life of the general Dutch population and patients with other chronic diseases.ResultsAt baseline, quality of life was assessed in 248 SLE patients, of whom 98 had NPSLE (39.7%). Follow-up data were available for 104 patients (42%), of whom 64 had NPSLE (61.5%). SLE patients presenting neuropsychiatric symptoms showed a significantly reduced quality of life in all subscales of the SF-36. Quality of life at follow-up showed a significant improvement in physical functioning role (p = 0.001), social functioning (p = 0.007), vitality (p = 0.023), mental health (p = 0.014) and mental component score (p = 0.042) in patients with neuropsychiatric symptoms not attributed to SLE, but no significant improvement was seen in patients with NPSLE.ConclusionQuality of life is significantly reduced in patients with SLE presenting neuropsychiatric symptoms compared with the general population and patients with other chronic diseases. Quality of life remains considerably impaired at follow-up. Our results illustrate the need for biopsychosocial care in patients with SLE and neuropsychiatric symptoms.
“…Calf thymus-derived chromatin and total histones tested positive for monoclonal antibodies against non-modified and modified histones [8–10]. Measurements of anti-dsDNA antibodies in Crithidia and Farr assays were performed according to local standards, as previously described [30,31]. …”
Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features. Plasma from SLE patients with and without lupus nephritis, disease controls, and healthy controls, were tested in ELISA with histone H4 peptide acetylated at lysines 8, 12 and 16 (H4pac), H2B peptide acetylated at lysine 12 (H2Bpac), H3 peptide trimethylated at lysine 27 (H3pme), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4pac showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bpac exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3pme appeared not specific for SLE. Anti-H4pac and anti-H2Bpac reactivity demonstrated a high correlation with disease activity. Moreover, patients reacting with multiple modified histone peptides exhibited higher SLEDAI and lower C3 levels. SLE patients with renal involvement showed higher reactivity with H2B/H2Bpac and a more pronounced reactivity with the modified equivalent of H3pme and H2Bpac. In conclusion, reactivity with H4pac and H2Bpac is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bpac is in particular associated with lupus nephritis.
“…Plasmas were collected from patients with biopsy-proven proliferative lupus nephritis (at that time classified as WHO class III or IV (Churg et al 1995) included in the first (Grootscholten et al 2006;Arends et al 2012) or second Dutch Lupus Nephritis Study (Arends et al 2014).…”
Autoantibodies against nucleosomes are considered a hallmark of systemic lupus erythematosus (SLE). We compared in patients with proliferative lupus nephritis the diagnostic usefulness of a dsDNA-loaded nucleosome ELISA (anti-dsDNA-NcX) with ELISAs in which dsDNA or nucleosomes alone were coated. First, we analysed whether DNA loading on nucleosomes led to masking of epitopes by using defined monoclonal anti-DNA, anti-histone and nucleosome-specific autoantibodies to evaluate the accessibility of nucleosomal epitopes in the anti-dsDNA-NcX ELISA. Second, autoantibody levels were measured in these 3 ELISAs in 100 patients with proliferative lupus nephritis (LN) before immunosuppressive treatment and in 128 non-SLE disease controls. In patients with LN inter-assay comparisons and associations with clinical and serological parameters were analysed. The panel of monoclonal antibodies revealed that all epitopes were equally accessible in the anti-dsDNA-NcX ELISA as in the two other ELISAs. Patients with proliferative lupus nephritis were positive with dsDNA-loaded nucleosomes in 86%, with DNA in 66% and with nucleosomes in 85%. In the non-lupus disease control group these frequencies were 1.6% (2 out of 128) for both the anti-dsDNA-NcX and the anti-dsDNA ELISA and 0% in the anti-nucleosome ELISA. The levels in the anti-dsDNA-NcX ELISA were high in a group of patients with LN that showed absent reactivity in the anti-DNA or low levels in the anti-nucleosome ELISA. Anti-dsDNA-NcX positivity was associated with higher SLEDAI scores within this group. Within nucleosome-based ELISAs, we propose the anti-dsDNA-NcX ELISA as the preferred test system.
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