Autoantibodies against the complement component C1q (anti-C1q) are among the main biomarkers in lupus nephritis (LN) known to contribute to renal injury. C1q, the recognition subcomponent of the complement classical pathway, forms a heterotetrameric complex with C1r and C1s, and can also associate a central complement regulator and C1 Inhibitor (C1-Inh). However, the frequency and the pathogenic relevance of anti-C1r, anti-C1s and anti-C1-Inh autoantibodies remain poorly studied in LN. In this paper, we screened for anti-C1q, anti-C1r, anti-C1s and anti-C1-Inh autoantibodies and evaluated their association with disease activity and severity in 74 LN patients followed up for 5 years with a total of 266 plasma samples collected. The presence of anti-C1q, anti-C1r, anti-C1s and anti-C1-Inh was assessed by ELISA. IgG was purified by Protein G from antigen-positive plasma and their binding to purified C1q, C1r and C1s was examined by surface plasmon resonance (SPR). The abilities of anti-C1q, anti-C1r and anti-C1s binding IgG on C1 complex formation were analyzed by ELISA. The screening of LN patients’ plasma revealed 14.9% anti-C1q positivity; only 4.2%, 6.9% and 0% were found to be positive for anti-C1r, anti-C1s and anti-C1-Inh, respectively. Significant correlations were found between anti-C1q and anti-dsDNA, and anti-nuclear antibodies, C3 and C4, respectively. High levels of anti-C1q antibodies were significantly associated with renal histologic lesions and correlated with histological activity index. Patients with the most severe disease (A class according to BILAG Renal score) had higher levels of anti-C1q antibodies. Anti-C1r and anti-C1s antibodies did not correlate with the clinical characteristics of the LN patients, did not interfere with the C1 complex formation, and were not measurable via SPR. In conclusion, the presence of anti-C1q, but not anti-C1s or anti-C1r, autoantibodies contribute to the autoimmune pathology and the severity of LN.
Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). LN often leads to kidney failure, affecting the quality of a patient's life. There are several classical biomarkers that assist nephrologists' daily practice. For more than 50 years, anti-double stranded DNA antibodies and complement components C3 and C4 have been used for LN disease activity evaluation. The major obstacle in the usage of conventional biomarkers is that none of them have both high specificity and high sensitivity. Moreover, an invasive kidney biopsy is still the gold standard for renal involvement detection in SLE patients. Therefore, new non-invasive biomarkers are needed for the early and accurate establishment of LN. Among the promising candidates are long non-coding RNAs (lncRNAs). Their dysregulation appears to have predictive and diagnostic potential. Furthermore, these biomarkers like other conventional biomarkers give insight into the pathogenesis of LN. This review aims to summarize the available information on lncRNAs in SLE patients and to present their future opportunities to add to the conventional biomarkers in the diagnosis and monitoring of LN.
Systemic lupus erythematosus (SLE) is severe, chronic autoimmune disease affecting mainly young active individuals, leading to disability and premature death. Recent studies have reported long non-coding RNAs (lncRNAs) to participate in the pathogenesis of the disease. Among lncRNAs, the circular RNAs (circRNAs) gain growing scientific attention due to their stability in body fluids. This makes them suitable for new nonbiomarkers for evaluation of SLE activity and promising therapeutic targets. Methods for detecting of cir-cRNAs are evolving rapidly. The aim of this review is to present these techniques and their advantages and disadvantages.
Системата на комплемента представлява важна част от имунния отговор. Нормалното й функциониране е задължително за защитата на организма от патогени, както и за очистването му от имунни комплекси, апоптотични клетки и клетъчен дебрис. Прекалената й активация обаче може да доведе до отделяне на множество про-инфламаторни и цитотксични медиатори, причиняващи възпаление и тъканна увреда. Участието на комплемента в патогенезата на ревматоидния артрит (РА) е безспорно, но интимните механизми, по които то се осъществява и съответно възможностите за повлияването им, са все още обект на изследвания. Целта на настоящия обзор е да очертае и систематизира събраните до момента научни доказателства в това отношение.
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