SLICC/ACR Damage Index Research Articles

Anti-dsDNA and anti-Sm antibodies do not predict damage in systemic lupus erythematosus

We aimed to determine whether anti-dsDNA and anti-Sm antibodies predict damage in systemic lupus erythematosus (SLE). Five-hundred inception patients from the University of Toronto Lupus Clinic were studied. Predictors assessed for the entire study period were: (1) raised anti-dsDNA on two consecutive occasions; (2) anti-dsDNA levels (normal, mildly or highly elevated); (3) presence of antiSm on any occasion. To account for disease duration, the following were assessed at three years post-inception: raised anti-dsDNA on two consecutive occasions; anti-dsDNA levels. These predictors were correlated with the following outcomes: (1) overall SLICC/ACR Damage Index (SDI) at the end of the study period; (2) frequency of damage in the cardiovascular, neuropsychiatric, musculoskeletal and renal components of SDI; ((3) SDI at five years for the predictors assessed at three years post-inception. In the multivariate analysis, presence of anti-DNA antibodies or of anti-SM were non-significant but sex, age at SLE diagnosis, disease duration, corticosteroid use and cumulative dose were strong predictors of damage. Raised anti-dsDNA on two occasions or anti-dsDNA levels in the three years post-inception patients did not predict damage at five years. The presence and levels of anti-dsDNA and anti-Sm antibodies do not predict damage in SLE.

Interleukin-10 gene polymorphisms are associated with the SLICC/ACR Damage Index in systemic lupus erythematosus

Overproduction of interleukin-10 (IL-10) is a pivotal feature in the pathophysiology of systemic lupus erythematosus (SLE). We examined the IL10 genotype of Korean patients with SLE and normal controls to determine whether associations exist between the pattern of inherited IL10 genes and SLE susceptibility or the SLICC/ACR Damage Index (SDI). A total of 350 Korean SLE patients and 330 healthy subjects were enrolled. Direct DNA sequencing and primer extension procedures were employed. Logistic regression analyses were performed to examine the genetic association with SLE and SDI. Eight sequence variants were identified by direct DNA sequencing in 24 Korean individuals. Five of the polymorphisms were selected for larger scale genotyping (n = 680) by considering their allele frequencies, haplotype-tagging status and linkage disequilibrium coefficients among polymorphisms. Haplotypes and allele distributions of the IL10 polymorphisms did not differ significantly between SLE patients and controls. Among identified SNPs, the rare C allele of IL10-592A-->C was significantly associated with the SDI among SLE patients in the following three alternative models: codominant (P = 0.007, odds ratio = 1.70), dominant (P = 0.02, odds ratio = 1.85) and recessive (P = 0.05, odds ratio = 2.25). Similarly, IL10+955T-->G and IL10-ht2 were significantly associated with the SDI in the codominant and dominant models. IL10 polymorphisms are not associated with disease susceptibility in Korean patients with SLE. However, IL10-592A-->C, IL10+955T-->G and IL10-ht2 are significantly associated with the SDI, suggesting that IL10-592C, IL10+955G and IL10-ht2 accelerate the damage induced by SLE.

Catalase and PPARg2 genotype and risk of systemic lupus erythematosus in Koreans

Catalase (CAT) and peroxisome proliferator activated receptor-gamma2 (PPARgamma2) are important regulators of oxidative stress and inflammation, which may contribute to the development of systemic lupus erythematosus (SLE). The objective of this study was to investigate the effects of genetic polymorphisms of CAT and PPARy2 on risk and severity of SLE in a Korean population. DNA was isolated from blood samples collected from 345 patients with SLE and 400 controls. Genotyping for the -262C-->T polymorphism of CAT and the Pro 12Ala polymorphism of PPARgamma2 were performed by PCR-RFLP analysis. The severity of SLE was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). No association was observed between genotypes for any of the clinical manifestations of SLE. CAT and PPARgamma2 genotypes were not associated with either risk or severity of SLE. For subjects who were carriers of the high activity T allele for CAT and have the Pro/Pro genotype for PPARgamma2, the odds ratio (95% confidence interval) for risk of SLE was 0.45 (0.23-1.08). Our results suggest that genetic polymorphisms of CAT and PPARy2 do not play a significant role in the development of SLE in a Korean population. A possible protective effect of a combined genotype warrants further investigation.

Analysis of the relationship between disease activity and damage in patients with systemic lupus erythematosus--a 5-yr prospective study.

To determine whether initial damage, disease duration, age, initial health status, average disease activity over the 5 yr or an average medication score covering the follow-up period would predict an increase in damage in patients with systemic lupus erythematosus (SLE) within the next 5 yr. A 5-yr prospective longitudinal study of a cohort of 141 consecutive patients with SLE attending a specialist lupus out-patient clinic in London from their first assessment between July 1994 and February 1995. Disease activity was assessed using the BILAG system, initial health status by the Medical Outcome Survey Short Form 20 with an extra question about fatigue (SF-20+) and damage by the SLICC/ACR Damage Index (SDI). Damage was reassessed 5 yr later. Statistical analysis was carried out using multiple logistic regression analysis (logXact). One hundred and thirty-three female and eight male SLE patients (97 Caucasians, 16 Afro-Caribbeans, 22 Asians and 6 others) were included, their age at inclusion was 41.1 +/- 12.5 yr and their disease duration 10.2 +/- 6.3 yr. The mean measures at inclusion were: total BILAG 5.2 (range 0-17), total SDI 1.2 (0-7) and medication score 1.2 (0-3). Six patients were lost to follow-up because they had moved. Of the remaining 135 patients total damage had increased in 40 patients and 10 patients had died. At the end of the study, at 4.63 +/- 0.19 yr, the total SDI had increased to 1.6 +/- 1.7. Multiple logistic regression analysis revealed that death and increase in damage were strongly predicted by a high total disease activity over the entire study period (P<0.001) as we had hypothesized. When the total BILAG score was replaced by the average number of A-flares the prediction of accrual of damage during the study period was again highly significant (P = 0.004). In this first prospective study of its type a highly significant impact of total disease activity, as measured over 5 yr using the BILAG system, on the development of total damage was revealed. Moreover, these results provide further proof of the validity of the SDI and support the BILAG concept of the A-flares.

Contribuição da doença e sua terapêutica no índice de dano SLICC/ACR na fase precoce do lúpus eritematoso sistêmico

The majority of the information available about the disease course of patients with systemic lupus erythematosus (SLE) is restricted to the first five years after disease onset. However, data about early damage were rarely reported. to describe the early damage outcome of SLE patients in early disease and to discriminate the influence of disease itself or its therapy as the main cause of their damage. we retrospectively studied 82 patients with SLE, diagnosed during the period from 1998 to 1999 in our institution. In all patients the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) was scored at the diagnosis and annually for the next three years. Clinical manifestations were evaluated at each visit as well as the therapy. The SLICC/ACR-DI scores for each organ system and the prevalence of damage within organ systems were assessed, as well as its possible main cause (disease or therapy). the mean age at entry was 31.6 years with female predominance of 94%. The majority of the patients (94%) presented cutaneous and articular involvement, 40% renal, 28% pulmonary, and 18% neurological manifestations. At the end of the study, 52 (63.4%) patients had no damage to score with SLICC. From the remaining 30 patients, 16 had a score of 1 and 14 had a score = 2. In total, 36 damages occurred, 23 of them attributed to the disease and 13 to the therapy (64% vs. 36%; p < 0.05). The most frequently injured systems were the articular and the neurological (27.7%) ones, followed by the renal (13.8%) system. All patients with neurological involvement have early damage due to the disease itself in spite of the aggressive therapeutic whereas from 10 patients with articular damage, 70% (7) were associated with steroid therapy (osteonecrosis). In contrast, premature renal injury was observed in 13.8%, all of them with unresponsive severe nephritis. Other adverse effect of therapy included 1 angina, 2 cataracts, 1 diabetes and 2 premature menopauses. this study suggests that early damage is still a major problem in SLE that reinforces the need for new strategies in order to minimize injury, particularly for neurological manifestations. Moreover, it also seems important to reduce morbidity induced by corticosteroid therapy with the use of steroid-sparing agents.