Anti-C1q antibodies in lupus nephritis and their correlation with the disease activity.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disorder. Renal involvement usually develops in the first few years of illness and should be detected early by periodic urine analysis and quantitation of proteinuria. The aim of our work was to evaluate the biological marker [anti-complement 1q antibodies (anti-C1q Ab)] in lupus nephritis (LN) patients and its correlation to SLE disease activity. Sixty-five subjects were divided into four groups; Group I: SLE patients with LN (proteinuria >0.5 g/day), Group II: SLE patients without LN (all of them had a lupus flares rather than nephritis; active nonrenal), Group III: SLE patients without any activity (inactive disease), and Group IV: Control group. All subjects underwent urine analysis, complete blood picture, liver function tests, kidney function tests, albumin/ creatinine ratio, antinuclear antibody, anti-double stranded DNA (anti-dsDNA) antibody, C3, C4, and anti-C1q Ab. All patients in the first group underwent renal biopsy and pathological diagnosis showed: Class II in two patients, Class III and IV in nine patients, and Class V in four patients. Anti-C1q Ab were found in the serum of SLE patients and not in the control group and showed an association with active lupus with much higher concentration in active renal group, specifically those with severe renal histological lesions (proliferative form). There was significant statistical positive correlation between anti-C1q Ab with anti-dsDNA and SLE disease activity index in both active groups. There was statistically significant negative correlation between anti-C1q Ab with C3 and C4 in both active groups. Anti-C1q Ab could be used as useful marker for active lupus, especially with nephritis.

Zinc alpha 2 glycoprotein as an early biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus / Zinco-alfa2-glicoproteina (ZAG) como biomarcador precoce de nefropatia diabética em pacientes com diabetes mellitus tipo 2

Abstract Introduction: Although microalbuminuria remains the gold standard for early detection of diabetic nephropathy (DN), it is not a sufficiently accurate predictor of DN risk. Thus, new biomarkers that would help to predict DN risk earlier and possibly prevent the occurrence of end-stage kidney disease are being investigated. Objective: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) as an early marker of DN in type 2 diabetic (T2DM) patients. Methods: 88 persons were included and classified into 4 groups: Control group (group I), composed of normal healthy volunteers, and three patient groups with type 2 diabetes mellitus divided into: normo-albuminuria group (group II), subdivided into normal eGFR subgroup and increased eGFR subgroup > 120 mL/min/1.73m2), microalbuminuria group (group III), and macroalbuminuria group (group IV). All subjects were submitted to urine analysis, blood glucose levels, HbA1c, liver function tests, serum creatinine, uric acid, lipid profile and calculation of eGFR, urinary albumin creatinine ratio (UACR), and measurement of urinary and serum ZAG. Results: The levels of serum and urine ZAG were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied groups regarding serum and urinary ZAG was found. Urine ZAG levels were positively correlated with UACR. Both ZAG levels were negatively correlated with eGFR. Urine ZAG levels in the eGFR ˃ 120 mL/min/1.73m2 subgroup were higher than that in the normal eGFR subgroup. Conclusion: These findings suggest that urine and serum ZAG might be useful as early biomarkers for detection of DN in T2DM patients, detectable earlier than microalbuminuria.

Resumo Introdução: Embora a microalbuminúria continue sendo o padrão ouro para a detecção precoce da nefropatia diabética (ND), ela não é um preditor suficientemente preciso do risco de ND. Assim, novos biomarcadores para prever mais precocemente o risco de ND e possivelmente evitar a ocorrência de doença renal terminal estão sendo investigados. Objetivo: Investigar a zinco-alfa2-glicoproteína (ZAG) como marcador precoce de ND em pacientes com debates mellitus tipo 2 (DM2). Métodos: Os 88 indivíduos incluídos foram divididos em quatro grupos: grupo controle (Grupo I), composto por voluntários saudáveis normais; e três grupos de pacientes com DM2 assim divididos: grupo normoalbuminúria (Grupo II), subdivididos em TFG normal e TFG > 120 mL/min/1,73 m2), grupo microalbuminúria (Grupo III) e grupo macroalbuminúria (Grupo IV). Todos foram submetidos a urinálise e exames para determinar glicemia, HbA1c, função hepática, creatinina sérica, ácido úrico, perfil lipídico, cálculo da TFG, relação albumina/creatinina (RAC) e dosagem urinária e sérica de ZAG. Resultados: Os níveis séricos e urinários de ZAG foram mais elevados nos pacientes com DM2 em comparação aos controles. Foi identificada diferença estatisticamente significativa entre os grupos estudados em relação aos níveis séricos e urinários de ZAG. Os níveis urinários de ZAG foram positivamente correlacionados com a RAC. Ambos os níveis de ZAG foram negativamente correlacionados com TFG. Os níveis urinários de ZAG no subgrupo com TFG ˃ 120 mL/min/1,73m2 foram maiores do que no subgrupo com TFG normal. Conclusão: Constatamos que a ZAG sérica e urinária pode ser um útil biomarcador precoce para detecção de ND em pacientes com DM2, sendo detectável mais precocemente que microalbuminúria.

Serum Levels of Transforming Growth Factor Beta -1 (TGF-ß1) as An Early No Invasive Marker for Diagnosis of Lupus Nephritis in Systemic Lupus Erythematosus Patients.

About 40-50% of all patients with systemic lupus erythematosus (SLE) patients are associated with significant morbidity and a poor prognosis. The transforming growth factor ß-1(TGF-ß1) is a member of cytokines families which has emerged as an important player in the pathogenesis of autoimmune diseases, including SLE. In this study we aimed to evaluate TGF-ß1 as a noninvasive diagnostic test for early diagnosis of LN and to assess the correlations between TGFß-1 and clinic-pathologic characteristics as well as disease activity of SLE. This case-control study included 188 patients with SLE, stratified into two subgroups LN group and Non-LN group. We assessed diseases activity by SLE disease activity index and measured TGEß-1 by using ELISA. Our results showed that LN patients had significant lower values of serum TGF-ß1 compared with non-LN patients (P < 0.001). Moreover, there were significant differences between LN histopathological classes. The lowest levels values of serum TGFß1 was in Class V. There were significant negative correlations between levels of TGF-ß1 and SLEDAI, fever, arthritis, proteinuria, hematuria, serum creatinine, thrombocytopenia, lymphopenia, ESR, ANA, pus cell and cellular cast's, all (P < 0.01). In lupus nephritis patients, TGF-ß1 levels were positively correlated with eGFR, C3 and C4 (P < 0.001). Linear regression analysis revealed that, eGFR, CRP, thrombocytopenia, and serum creatinine were independently correlated with TGF-ß1 among lupus nephritis patients (P < 0.001). According to Receiver Operating Characteristic analysis, the sensitivity and specificity of TGF-ß1 were 91% and 65.5%, respectively in the diagnosis of LN among SLE patients. As LN group had significantly lower values of serum TGFß1 and the values further decreased with more damage of kidney tissues and progression of SLE activity. We conclude that serum TGF- ß1 could be a valuable non-invasive marker for assessment of LN activity and organ damage.

Zinc alpha 2 glycoprotein as an early biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus.

INTRODUCTION: Although microalbuminuria remains the gold standard for early detection of diabetic nephropathy (DN), it is not a sufficiently accurate predictor of DN risk. Thus, new biomarkers that would help to predict DN risk earlier and possibly prevent the occurrence of end-stage kidney disease are being investigated. OBJECTIVE: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) as an early marker of DN in type 2 diabetic (T2DM) patients. METHODS: 88 persons were included and classified into 4 groups: Control group (group I), composed of normal healthy volunteers, and three patient groups with type 2 diabetes mellitus divided into: normo-albuminuria group (group II), subdivided into normal eGFR subgroup and increased eGFR subgroup > 120 mL/min/1.73m2), microalbuminuria group (group III), and macroalbuminuria group (group IV). All subjects were submitted to urine analysis, blood glucose levels, HbA1c, liver function tests, serum creatinine, uric acid, lipid profile and calculation of eGFR, urinary albumin creatinine ratio (UACR), and measurement of urinary and serum ZAG. RESULTS: The levels of serum and urine ZAG were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied groups regarding serum and urinary ZAG was found. Urine ZAG levels were positively correlated with UACR. Both ZAG levels were negatively correlated with eGFR. Urine ZAG levels in the eGFR ˃ 120 mL/min/1.73m2 subgroup were higher than that in the normal eGFR subgroup. CONCLUSION: These findings suggest that urine and serum ZAG might be useful as early biomarkers for detection of DN in T2DM patients, detectable earlier than microalbuminuria.

Prevalence of occult hepatitis C virus infection in patients who achieved sustained virologic response to direct-acting antiviral agents.

The reappearance of HCV infection months or years after sustained virologic response (SVR) may be due to the persistence of HCV in tissue cells in spite of being undetected in serum. This situation is known as occult hepatitis C infection (OCI). We aimed to assess the prevalence of OCI in Egyptian patients with chronic hepatitis C (CHC) who achieved SVR after treatment with direct-acting antiviral agents (DAA). We carried out a cross-sectional study at the Advanced Center for Liver Diseases of Zagazig University Hospitals and Al-Ahrar Viral Hepatitis Treatment Center, Sharkia Governorate, Egypt. One hundred and fifty adult patients with CHC, who achieved SVR 12-24 weeks after end of treatment with sofosbuvir/daclatasvir ± ribavirin (139 patients, 92.67%), sofosbuvir/ledipasvir ± ribavirin (eight patients, 5.33%), sofosbuvir/simeprevir (two patients, 1.33%), and ombitasvir/ paritaprevir/ritonavir + ribavirin (one patient, 0.67%), according to the Egyptian National Committee for Control of Viral Hepatitis, were included in the study. We tested these patients for HCV RNA in peripheral blood mononuclear cells (PBMCs) immediately after confirmation of SVR12-24 weeks. Statistical analysis was performed by means of the Shapiro-Wilk test, Mann-Whitney U test, Chi-square test, and Fisher's exact test. Seventeen patients (11.33%) were positive for PBMNCs HCV RNA. The prevalence of OCI was highest in patients treated with simeprevir/sofosbuvir (2/2 patients). There is a substantially high prevalence of OCI after treatment with DAAs. We recommend dual testing for HCV RNA in both serum and PBMCs at the end of treatment of HCV infection with DAAs and during validation of the SVR following the initial response.