الفهرس 
Chapter (I)Only 14 pages are availabe for public view
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Abstract
Systemic lupus erythematosus (SLE) is an immune-mediated multi- systemic disease characterized by a wide variability of clinical manifestations and a course frequently subject to unpredictable flares. Lupus nephritis (LN) is one of the most common manifestations of SLE, affecting approximately 40% of patients with lupus. It represents a major risk factor for morbidity and mortality, and 10% of patients with LN will develop end-stage kidney disease. The gold standard for the diagnosis and assessment of LN is a kidney biopsy despite being an invasive procedure associated with many complications, therefore we need an easily available and non-invasive biomarkers that could be useful for monitoring LN disease activity and for assessing the response to induction treatment to determine the consequence for the use of immunosuppression Several novel urinary biomarkers for active LN have been identified, among these proteins is the activated leukocyte cell adhesion molecule ALCAM or CD166 which is a surface transmembrane glycoprotein from the immunoglobulin superfamily and is expressed on antigen presenting cells including macrophages, B cells, and more particularly on dendritic cells and serves as a CD6 ligand, co-stimulating T cells and enabling immune cell adhesion through CD6 binding or through ALCAM- ALCAM interactions. When CD6 associates with its ligand ALCAM, it co-stimulates T- cell activation, proliferation, recruitment and activation, which contribute to tissue inflammation and drives the pathogenesis of LN.
The aim of this study was to investigate the level of urinary ALCAM in SLE patients and study its clinico-serological relationship in SLE activity and severity. Our aim expanded to clarify the associations of this biomarker with LN activity and histopathology. The present study was a case–control study including 60 individuals with SLE [47 females (78.3%) and 13 males (21.7%)] as group I (patients’ group) who were subdivided according to the presence of LN into 2 subgroups: 30 SLE patients without LN (Ia) and SLE 30 patients with LN (Ib) and was conducted between September 2021 and September 2022.A 20 age and sex-matching subjects who were apparently healthy served as controls (group II).
Results of the present study showed that:
The mean age of the patients was 29.27 ± 5.07 years and their disease duration was 5.83 ± 0.61 and 5.63 ± 0.61 years for SLE patients with and without LN respectively.
Concerning the clinical manifestations among our SLE patients, the most frequent clinical variables at presentation was LN and malar rash representing 50% and 41.7% respectively, followed by arthritis and anemia in 28.3% then fever, leucopenia and thrombocytopenia in 21.7%; pericarditis and alopecia in 16.7%; pleurisy in 15.0%; lymphadenopathy in 10.0%; oral ulcer in 8.3%; myositis in 6.7%; headache in 3.3% and discoid lesion in 1.7%.
Regarding the serological manifestations of SLE patients, it was observed that there were highly statistically significant differences between SLE patients with and without nephritis as regards to hemoglobin percentage (HB%), s.albumin level, albuminurea, 24h urine protein and ESR (p<0.001) and a statistically significant difference as regards to blood urea level (p=0.019).
The SLEDAI in LN patients with was greater than that of SLE patients without nephritis with a statistically significant difference between both groups (p=0.027).
The mean uALCAM level was significantly increased in active LN patients compared to active SLE patients without renal involvement (491.0 vs
260.0 ng/mg, p <0.001), inactive LN patients (491.0 vs 160.0 ng/mg, p
<0.001), inactive SLE patients without renal involvement (491.0 vs 144.0 ng/mg, p < 0.001), and healthy controls (491.0 vs 92.0 ng/mg, p < 0.001).
The uALCAM level was significantly different among renal biopsy classes, SLEDAI grades and rSLEDAI (p<0.001).
The mean uALCAM level was different among SLE clinical features compared to others. It was statistically significantly higher associating the malar rash, arthritis, nephritis, anemia, leucopenia, and anti-dsDNA abs (p<0.001 each), and statistically significantly high with fever (p=0.001), lymphadenopathy (p=0.01), oral ulcer (p=0.012), alopecia (p=0.001), myositis (p=0.047), pericarditis (p=0.001), pleurisy (p=0.002), and thrombocytopenia (p=0.039). Insignificant associations of uALCAM occurred with discoid lesions (p<0.214), and headache (p<0.918).
There was a highly statistically significant positive correlation of uALCAM level with the SLEDAI score, rSLEDAI score , SLE disease duration, ESR, 24 hr urinary protein, hematuria, pyuria, and urea level (p<0.00) and a highly statistically significant negative correlation of uALCAM level with the s.albumin and C3 levels (p<0.001), and a statistically significant negative correlation with C4 (p=0.005).
On conducting Logistic Regression Analysis for the prediction of LN occurrence by using age, gender, laboratory data, SLEDAI and rSLEDAI grades, and uALCAM level as confounders, in univariate
analysis, higher levels of s.creatinine, urea level, 24 hr urinary protein, anti-dsDNA abs, SLEDAI score, rSLEDAI score, lower s.albumin level were associated with a risk of LN occurrence among SLE cases while on conducting multivariate analysis on univariate analysis significant confounders, only a higher 24 hr urinary protein, the SLEDAI score, the rSLEDAI score and the uALCAM levels were considered unfavorable risk predictors for LN occurrence.
On conducting Logistic regression analysis for the prediction of active LN by using age, gender, laboratory data, disease duration, SLEDAI score and rSLEDAI score and uALCAM level as confounders, in univariate analysis; higher values of ESR, s.creatinine level, urea level, 24 hr urinary protein level, anti-dsDNA abs, SLEDAI score, rSLEDAI score, lower s.albumin level, and a shorter disease duration were associated with the risk of active LN occurrence
However, multivariate analysis was conducted on significant confounders in univariate analysis, and revealed that only higher levels of the SLEDAI score, rSLEDAI score and uALCAM were considered unfavorable risk predictors for LN activity.