Cut-off values of immunological tests to identify patients at high risk of severe lupus nephritis

Cut-off values for anti-dsDNA, anti-nucleosome and anti-C1q antibodies tests and for complement-mediated hemolytic activity (CH50) were explored to identify patients with high risk of developing severe lupus nephritis (LN). Forty-one patients with confirmed systemic lupus erythematosus (SLE) were identified; their levels for the three antibodies and complement had been measured on a same serum sample. These patients were classified based on the presence of renal involvem ent; sixteen had active proliferative LN. With the cut-off values accepted in the laboratory for SLE diagnosis (anti-dsDNA > 100 UI/ml, anti-nucleosome > 50 U/ ml or CH50 < 190 UCH50%) no significant differences were found between patients with and without LN. Anti-C1q > 40 U/ml showed a statistically significant association with LN and had 80% of specificity. Cut-off values for LN identified by Receiver Operating Characteristic curves (ROC) were higher for anti-dsDNA (> 455 IU/ml) and anti-nucleosome (>107 U/ml), lower for CH50 (< 150 UCH50%) and, for anti-C1q (> 41 U/ml) coincided with the cut-off values accepted for SLE. Anti-C1q > 134 U/ml had a 92% of specificity, 56% of sensibility and was associated with a fifteen-fold increased risk of LN. The simultaneous presence of anti-nucleosome > 107 U/ml and anti-C1q > 134 U/ml was associated with a 27-fold higher probability for LN. According to these results, the cut-off values used to detect SLE activity could be inadequate to identify patients at high risk of severe LN.

Se exploraron valores de corte para los ensayos de anti-ADNdc, anti-nucleosoma, anti-C1q y complemento hemolítico total (CH50) capaces de identificar los casos con mayor riesgo de nefritis lúpica (NL) grave. Se seleccionaron 41 pacientes ≥ 16 años con lupus eritematoso sistémico (LES) confirmado que tenían titulados los niveles de los tres anticuerpos y CH50, en una misma muestra de suero. Fueron clasificados según presencia de compromiso renal; 16 presentaron formas proliferativas de NL activa. Con los valores de corte aceptados por el laboratorio para el diagnóstico de LES (anti-ADNdc > 100 UI/ml, anti-nucleosoma > 50 U/ml o un CH50 < 190 UCH50%) no se encontraron diferencias significativas entre casos con y sin NL. Un anti-C1q > 40 U/ml tuvo una especificidad del 80% y mostró una asociación estadísticamente significativa con NL. Al aplicar curvas Receiver Operating Characteristic (ROC) para NL, se identificaron valores de corte más altos para anti-ADNdc (> 455 IU/ml) y anti-nucleosoma (> 107 U/ml), más bajo para CH50 (< 150 UCH50%) y para el anti-C1q (> 41 U/ml) coincidió con el aceptado para diagnóstico de LES. Un anti-C1q > 134 U/ml presentó una sensibilidad del 56%, una especificidad del 92% y se asoció con quince veces más riesgo de NL. La presencia simultánea de anti-C1q > 134 U/ml y anti-nucleosoma > 107 U/ml se asoció 27 veces más riesgo de NL. De acuerdo a estos resultados los valores de corte empleados para actividad en pacientes con LES podrían resultar inadecuados para identificar pacientes con mayor riesgo de NL grave.

Anticorpos antinucleossomo e síndrome antifosfolipídica: estudo observacional / Antinucleosome antibodies and primary antiphospholipid syndrome: an observational study

OBJETIVO: Avaliar a associação entre a presença de anticorpos antinucleossomo (anti-NCS) e a síndrome antifosfolipídica primária (SAFP) e o posterior desenvolvimento de lúpus eritematoso sistêmico (LES). MATERIAIS E MÉTODOS: Trinta e seis mulheres com o diagnóstico de SAFP foram avaliadas prospectivamente para manifestações de doenças reumáticas autoimunes e para a presença de anticorpos antifosfolípides, anticorpos antinucleares e anti-NCS/cromatina. RESULTADOS: Após um período médio de seguimento de 45,7 meses, anticorpos anti-NCS/cromatina foram detectados em apenas uma paciente (2,8%), que desenvolveu manifestações de LES tais como poliartrite, linfopenia, neurite óptica, lesões compatíveis com esclerose múltipla em substância branca cerebral e perfil de autoanticorpos altamente sugestivo de LES. CONCLUSÃO: A frequência de anticorpos anti-NCS/cromatina é baixa em pacientes com SAFP, e sua presença pode associar-se ao desenvolvimento de manifestações de LES.

OBJECTIVE: To study the association of anti-nucleosome (anti-NCS) antibodies in primary antiphospholipid syndrome (APS) and the development of systemic lupus erythematosus (SLE) during follow-up. MATERIALS AND METHODS: Thirty-six women with primary APS were evaluated prospectively for clinical features of systemic autoimmune diseases and for the presence of antiphospholipid antibodies, antinuclear antibodies and anti-NCS/chromatin antibodies. RESULTS: After a mean follow-up period of 45.7 months, anti-NCS/chromatin antibodies were detected in only one patient (2.8%), who developed features of SLE including polyarthritis, lymphopenia, optic neuritis, multiple sclerosis-like lesions, and an autoantibody profile suggestive of SLE. CONCLUSION: The frequency of anti-NCS/chromatin antibodies in primary APS patients is very low, and they may be associated with the development of SLE manifestations.

Anti-Nucleosome antibodies as a diagnostic tool in systemic lupus erythematosus and marker of lupus nephritis

To evaluate the prevalence of anti-nucleosome antibodies [anti-NCS Abs] in systemic lupus erythematosus [SLE], their role in diagnosis, disease activity and lupus nephritis [LN]. The study was conducted on 23 SLE female patients. They were divided into two groups according to the presence or absence of LN. Ten apparently healthy individuals served as a control group. Clinical assessment was done to all patients especially for renal affection. Disease activity was scored with SLEDAI. Anti-NCS and anti-dsDNA antibodies were measured with ELISA. Renal biopsy was performed for patients with LN. The prevalence of anti-NCS Abs was [78.3%] and anti-dsDNA Abs was [56.5%] in SLE. Seventeen patients presented with LN and 6patients without. Among these patients, the prevalence of anti-NCS Abs and anti-dsDNA Abs were [88%-64.7%] and [50%-33.3%] respectively. Anti-NCS Abs were found to be positive in 21.7% of SLE patients lacking anti-dsDNA Abs. The mean anti-NCS and anti-dsDNA Abs tiler in SLE was 250.60 +/- 207.00 and 443.3 +/- 714.3 respectively, showing a highly significant increase compared with healthy controls [12.3 +/- 4.54 and 31.0 +/- 20.11] [p<0.001]. Moreover, in LN and those without LN, the mean anti-NCS Abs showed a highly significant increase [331.41 +/- 179. 73 and 21.67 +/- 8.36] [p<0.001], while there was a significant increase in the mean of anti-ds DNA Abs [574.71 +/- 794.07 and 71.17 +/- 46.99] [p<0.05] respectively. The sensitivity and specificity of anti-NCS Abs in SLE were 82.6% and 100% and in LN were 88.2% and 100% respectively. Anti-NCS Abs showed a positive significant correlation with ESR [r=0.900], SLEDAI [r=0.761] and anti-dsDNA Abs [r=0.681] in LN, but showed a negative significant correlation with disease duration [r=-0.511] and C4 [r=-0.650] in patients without LN. In LN 7 patients hadproliferative glomerular lesion [WHO class III], 6 patients class IV and 4 patients class II on renal biopsy. They were associated with a statistically significant proteinuria, anti-ds DNA and anti-NCS especially in classes II and IV, Anti-NCS Abs could be a useful parameter for diagnosis and assessment of disease activity and LN in SLE, It seems to be a more sensitive marker of SLE than anti-ds DNA especially in patients who are anti-dsDNA antibody negative

Anticorpos antinucleossomo em pacientes com lúpus eritematoso sistêmico juvenil / Antinucleosome antibodies in patients with juvenile systemic lupus erythematosus

Este estudo teve por objetivos avaliar a positividade do anticorpo antinucleossomo (anti-Ncs) no LES juvenil, sua associação com manifestações e atividade da doença e compará-lo ao anticorpo anti-DNA. A pesquisa dos anticorpos anti-Ncs e anti-DNA foi realizada em 74 pacientes com LESJ e 64 controles. Os anti-Ncs e anti-DNA demonstraram sensibilidade / The aims of this study were to evaluate the positivity of antinucleosome antibodies (Anti-Ncs) in SLE children, their association to disease manifestations and activity, and to compare them to anti-DNA antibodies. Anti-Ncs and anti-DNA were tested on 74 JSLE patients and 64 controls...