Self-Reported Physical Activity Is Associated with Lupus Nephritis in Systemic Lupus Erythematosus: Data from KORean Lupus Network (KORNET) Registry

PURPOSE: The aim of this study was to identify the associations among physical activity, disease activity, and organ damage in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: A total of 415 patients with SLE were consecutively enrolled from the KORean lupus Network (KORNET) registry. This registry assessed clinical features, disease activity [Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)], and organ damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI)] upon enrollment in the study. Self-reported physical activity was measured by the International Physical Activity Questionnaire. Statistical analyses were conducted using the Mann-Whitney U test and multivariate logistic regression analysis. RESULTS: A significant difference in vigorous activity was noted between patients with lupus nephritis (LN) (n=93) and those without LN (n=322) (p=0.012), but not in moderate and walking activities. In contrast, no differences in physical activity, walking, moderate, and vigorous intensity, according to SLEDAI-2K and SDI were found. In addition to younger age (p=0.032), high physical component summary of SF-36 (p=0.004) and SLEDAI-2K (p=0.038), and less vigorous physical activity were associated with LN (p=0.024). However, cardiovascular disease was not associated with physical activity in SLE patients. CONCLUSION: This study showed that patients with LN had less vigorous physical activity than patients without LN. The results suggest that lupus nephritis might be associated with physical activity.

Initial digital vasculitis in a large multicenter cohort of childhood-onset systemic lupus erythematosus / Vasculite digital inicial em uma grande coorte multicêntrica de pacientes com lúpus eritematoso sistêmico de início na infância

Abstract Objectives: To assess clinical digital vasculitis (DV) as an initial manifestation of childhood-onset systemic lupus erythematosus (cSLE) within a large population. Methods: Multicenter cross-sectional study including 852 cSLE patients (ACR criteria) followed in ten Pediatric Rheumatology centers in São Paulo State, Brazil. Results: DV was observed in 25/852 (3%) cSLE patients. Periungual hemorrhage was diagnosed in 12 (48%), periungual infarction in 7 (28%), tip finger ulceration in 4 (16%), painful nodules in 1 (4%) and gangrene in 1 (4%). A poor outcome, with digital resorption, occurred in 5 (20%). Comparison of patients with and without DV revealed higher frequency of malar rash (80% vs. 53%, p = 0.008), discoid rash (16% vs. 4%, p = 0.017), photosensitivity (76% vs. 45%, p = 0.002) and other cutaneous vasculitides (80% vs. 19%, p < 0.0001), whereas the frequency of overall constitutional features (32% vs. 61%, p = 0.003), fever (32% vs. 56%, p = 0.020) and hepatomegaly (4% vs. 23%, p = 0.026) were lower in these patients. Frequency of female gender, severe multi-organ involvement, autoantibodies profile and low complement were alike in both groups (p > 0.05). SLEDAI-2K median, DV descriptor excluded, was significantly lower in patients with DV compared to those without this manifestation [10 (0-28) vs. 14 (0-58), p = 0.004]. Visceral vasculitis or death were not observed in this cSLE cohort. The frequency of cyclophosphamide use (0% vs. 18%, p = 0.014) was significantly lower in the DV group. Conclusion: Our large multicenter study identified clinical DV as one of the rare initial manifestation of active cSLE associated with a mild multisystemic disease, in spite of digital resorption in some of these patients.

Resumo Objetivos: Avaliar a vasculite digital (VD) clínica como uma manifestação inicial do lúpus eritematoso sistêmico de início na infância (LESi) em uma grande população. Métodos: Estudo transversal multicêntrico que incluiu 852 pacientes com LESi (critérios do ACR), acompanhados em dez centros de reumatologia pediátrica do Estado de São Paulo. Resultados: Observou-se VD em 25/852 (3%) pacientes com LESi. Diagnosticaram-se hemorragia periungueal em 12 (48%), infarto periungueal em sete (28%), úlcera de ponta de dígito em quatro (16%), nódulos dolorosos em um (4%) e gangrena em um (4%). Um desfecho ruim, com reabsorção digital, ocorreu em cinco (20%) pacientes. A comparação entre pacientes com e sem VD revelou maior frequência de erupção malar (80% vs. 53%, p = 0,008), erupção discoide (16% vs. 4%, p = 0,017), fotossensibilidade (76% vs. 45% p = 0,002) e outras vasculites cutâneas (80% vs. 19%, p < 0,0001), enquanto a frequência de características constitucionais totais (32% vs. 61%, p = 0,003), febre (32% vs. 56% p = 0,020) e hepatomegalia (4% vs. 23%, p = 0,026) foram menores nesses pacientes. A frequência do gênero feminino, o envolvimento grave de múltiplos órgãos, perfil de autoanticorpos e baixo complemento foram semelhantes nos dois grupos (p > 0,05). A mediana no Sledai-2 K, exclusive o descritor de VD, foi significativamente menor nos pacientes com VD em comparação com aqueles sem essa manifestação [10 (0 a 28) vs. 14 (0 a 58), p = 0,004]. Não foram observadas vasculite visceral nem morte nessa coorte de pacientes com LESi. A frequência de uso de ciclofosfamida (0% vs. 18%, p = 0,014) foi significativamente menor no grupo VD. Conclusão: Este grande estudo multicêntrico identificou a VD clínica como uma rara manifestação inicial do LESi ativo, associada a doença multissistêmica leve, apesar da ocorrência de reabsorção digital em alguns desses pacientes.

Cytokine profile in childhood-onset systemic lupus erythematosus: a cross-sectional and longitudinal study

Childhood-onset systemic lupus erythematosus (cSLE) exhibits an aggressive clinical phenotype and severe complications. This could be due to a pro-inflammatory cytokine milieu. Therefore, we determined plasma levels of Th1 (IL-2, IFN-γ, TNF), Th2 (IL-4), Th17 (IL-17A, IL-6), and Treg (IL-10) cytokines in a cohort of cSLE patients and healthy controls, and we evaluated the association between these cytokines and disease activity. We conducted a cross-sectional study with 51 cSLE patients from two pediatric rheumatology services. Ten cSLE patients participated in a longitudinal follow-up study. Blood samples were collected from the same patient during active and inactive disease. Disease activity was evaluated according to SLE Disease Activity Index 2000 (SLEDAI-2K). Cytokines levels were measured by cytometric bead array technique. cSLE patients had higher IL-6 (P<0.001) and IL-10 (P<0.001) levels than healthy controls. Patients with active disease had higher IL-6 and IL-10 levels than patients with inactive disease (P=0.001 and P=0.014, respectively) and the control group (both P<0.001). IL-6 (P=0.022), IL-10 (P=0.013), and IL-17A (P=0.041) levels were significantly higher during active than inactive disease. Linear regression analysis revealed IL-6 (P=0.002, 95%CI=0.006-0.025) and IL-10 (P=0.01 95%CI=0.021-0.150) as independent factors for increased SLEDAI-2K. IL-6, IL-10, and IL-17A are candidate biomarkers for disease activity in cSLE patients. This is the first longitudinal study to support their pivotal role in the pathogenesis of the disease.

Anticuerpos antinucleosoma frente a marcadores inmunológicos convencionales en el diagnóstico de la actividad del lupus eritematoso sistémico / Anti-nucleosome antibodies against conventional Immunological markers in the diagnosis of SLE activity

OBJETIVOS: examinar el perfil de anticuerpos en pacientes con lupus eritematoso sistémico y establecer la correlación entre los niveles de anticuerpos y la actividad de la enfermedad y de la nefritis lúpica. MÉTODOS: en 213 pacientes con lupus eritematoso sistémico, atendidos de forma consecutiva, se determinaron los anticuerpos anti-DNA de doble cadena (DNAdc), antinucleosoma (Nu), anti-Sm, anti-RNP, anti-Ro, anti-La y anti-Scl-70 por ensayo inmunoadsorbente ligado a enzima (ELISA), el C3 y el C4. La actividad de la enfermedad fue evaluada por el índice SLEDAI-2K, sin la contribución de anti-DNAdc, C3 ni C4. Los niveles de anticuerpos, el complemento y la actividad del lupus eritematoso sistémico fueron correlacionados. RESULTADOS: los niveles de todos los anticuerpos resultaron superiores significativamente en los pacientes en fase activa de la enfermedad con respecto a los que se hallaban en la fase inactiva. Los coeficientes de correlación de Spearman más altos con la puntuación de SLEDAI-2K correspondieron a los anti-Nu y anti-DNAdc (p= 0,856 y p= 0,616, respectivamente, p < 0,001 para ambos). Las áreas bajo de la curva (AUC) del análisis COR de la actividad del LES fueron en orden decreciente para los anti-Nu= 0,948, anti-DNAdc= 0,810, anti-RNP= 0,705, C4= 0,704, anti-Sm= 0,703, C3= 0,688, anti-Scl-70= 0,611, anti-La= 0,601 y anti-Ro= 0,593; y de la actividad renal para los anti-Nu= 0,845, anti-DNAdc= 0,755, C4= 0,694, C3= 0,670, anti-Sm= 0,641, anti-RNP= 0,630, anti-Scl-70= 0,611, anti-Ro= 0,593 y anti-La= 0,567. CONCLUSIÓN: los anticuerpos anti-Nu mostraron una capacidad discriminatoria excelente para la actividad del LES y de la actividad renal lúpica, superior a la de los anti-DNAdc y el resto de los marcadores.

OBJECTIVES: to examine the profile of antibodies in patients with systemic lupus erythematosus and establish the correlation between antibody levels and disease activity, and lupus nephritis. METHODS: anti-double stranded DNA (dsDNA), antinucleosoma (Nu), anti-Sm, anti-RNP, anti-Ro, anti-La, and anti-Scl-70 antibodies by enzyme-linked immunosorbent assay (ELISA) as well as C3 and C4 were determined in 213 patients with systemic lupus erythematosus who were treated consecutively. Disease activity was assessed by the SLEDAI 2K-index, without the contribution of anti-dsDNA, C3 or C4. The levels of antibodies, complement and activity of systemic lupus erythematosus were correlated. RESULTS: the levels of antibodies turned out to be remarkably higher in patients in the active phase of the disease compared to those who were in the inactive phase. The higher Spearman correlation coefficients with SLEDAI-2K score corresponded to the anti-Nu and anti-dsDNA (p = 0.856 and p = 0.616, respectively, p <0.001 for both). The areas under the ROC curve analysis of the activity of systemic lupus erythematosus were in descending order as follows: anti-Nu = 0.948; anti-dsDNA = 0.810; anti-RNP = 0.705; C4 = 0.704; anti-Sm = 0.703; C3 = 0.688; anti-Scl-70 = 0.611; = 0.601 anti-La. Anti-Ro = 0.593; and renal activity for anti-Nu = 0.845; anti-dsDNA = 0.755; C4= 0.694; C3 = 0.670; anti-Sm = 0.641; anti-RNP = 0.630; anti-Scl-70 = 0.611; anti-Ro = 0.593 and anti-La = 0.567. CONCLUSION: the anti-Un exhibit excellent activity discriminating capacity of SLE lupus and renal activity, higher than the anti-dsDNA and other markers.