الفهرس 
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Abstract
Systemic Lupus Erythematosus is a heterogeneous clinical featured disorder characterized by altered self-tolerance mechanisms which are mainly due to the interaction of genetic, environmental and hormonal factors. The genetic component has a pivotal role in SLE pathogenesis with several genes contributing in disease´s triggering. The majority of genetic variations, including SNPs, associated with SLE are within immune response–related genes and Human leukocyte antigen gene variants.
Considering that CTLA-4 is an important negative regulator of T-cell responses and IL-1β is a potential pro-inflammatory cytokine, it seems that their allelic polymorphisms might have an effect on susceptibility to SLE.
This study was performed at Menoufia University Hospitals to investigate the polymorphisms of IL-1β and CTLA-4 genes in patients with SLE and a possible association between these polymorphisms and increased susceptibility and activity of SLE.
This study was carried out during the period from January 2017 to June 2018 and included 50 SLE patients (25 active and 25 inactive SLE) recruited on one of their routine visits to outpatient clinics of Internal Medicine and Rheumatology and Rehabilitation Departments as well as from inpatient ward of Internal Medicine at Menoufia University Hospitals and 25 age- and sex-matched healthy individuals.
All Patients were subjected to full history taking, complete medical examination and thorough laboratory investigations.
1) Personal history including: name, age, sex, occupation, residence, educational level and special habits.
2) Relevant clinical and medical data were collected with particular stress on onset of SLE, duration of disease and presence of family history of autoimmune diseases
3) Thorough clinical examination.
4) Laboratory investigations: Hematology and biochemistry analyses were performed at the local laboratory of the Menoufia University Hospitals. It included the following: CBC, ESR, kidney function tests, liver functions tests, ANA and Anti-ds DNA as well as complement C3 and complement C4.
5) Polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) was used to analyze the _318C/T polymorphism at the promoter region of the CTLA-4 gene and T-31C polymorphism in IL-1β gene.
In our study, all lupus patients were females. The mean ages of active and inactive SLE patients were 32.08±7.19 and 31.32 ±7.67 years old respectively. About 18% of lupus patients had positive family history of SLE. The mean ages of onset and disease duration in lupus patients were 25.61±4.53 and 5.97±3.97 years respectively. Half of lupus patients were inactive while 14% had mild activity. Moderate and severe lupus activity were diagnosed each in 18% of patients.
Malar rash, fever, arthritis, nephritis, alopecia, photosensitivity, oral ulcers, vasculitis and serositis were diagnosed in 76%, 72%, 52%, 52%, 48%, 48%, 44%, 32% and 16% of lupus patients respectively.
Hemoglobin level, WBCs count, platelet count, serum albumin, serum complement C3 and complement C4 were significantly lower in lupus patients compared to controls (P value <0.05). Mean anti-dsDNA levels, serum ALT, serum AST and ESR were significantly higher in lupus patients compared to controls (P value <0.05). Blood urea and serum creatinine were significantly higher in patients with active SLE compared to patients with inactive SLE and controls (P value <0.05). There is no significant difference between three studied groups regarding serum levels of total and direct bilirubin and INR bilirubin as P- value > 0.05.
In our study, there was no association between −318 CTLA-4 polymorphisms and SLE susceptibility or activity (P value >0.05). The CC genotype was observed in 78.0% of the SLE patients and 68.0% of the controls while 20% of the controls had TT genotype compared to 8% in lupus patients with no statistical significant difference.
Socio-demographic characters, relevant clinical and medical data, disease activity presented by SLEDAI, clinical manifestations and organ involvement as well as anti-dsDNA levels had no significant association with genotypic pattern of _318 C/T CTLA-4 polymorphisms (P-value ˃ 0.05). Except for hemoglobin level, laboratory investigations didn`t show any significant difference between different genotypes of _318 C/T CTLA-4 polymorphisms in lupus patients (P-value ˃ 0.05).
The −31 IL-1β TT genotype frequency was found to be significantly higher in SLE patients (26% vs. 8%) compared to healthy controls (p= 0.009). In our study, the risk of developing SLE was 3.67 and 8.27 times higher in individuals carrying C/T and TT genotypes respectively. The frequency of T allele was significantly higher in SLE patients (52% vs.26%) than in control (p=0.002; OR=3.08).
Individuals carrying TT genotype for IL-1β T-31C polymorphism were significantly higher in active SLE patients and the risk of SLE activity was 8.88 fold higher in these individuals [OR, 8.88 (95% CI, 1.39 to 56.57); P=0.04]. The frequency of T allele was significantly higher in patients with active SLE (64% vs. 40%) compared to patients with inactive SLE (P value 0.01; OR 2.66).
Socio-demographic characters, relevant clinical and medical data had no significant association with genotypic pattern of _−31 T/C IL-1β polymorphisms (P-value ˃ 0.05).
Lupus patients with TT genotype had higher mean SLEDAI score (12.90±5.41) compared to those with C/T and CC genotypes (8.41±4.62 and 4.66±3.78 respectively).
It was found that arthritis and vasculitis were more common with the TT genotype at −31 site in IL-1β gene (P value 0.03 and 0.04 respectively).
Lupus patients with TT genotype had significantly higher mean anti-dsDNA levels (162.33 + 94.21) compared to those with C/T and CC genotypes (88.07 + 62.21 and 72.45 + 27.83 respectively).
Except for ESR, laboratory investigations of lupus patients didn`t show any significant difference between different genotypes of −31 T/C IL-1β polymorphisms (P-value ˃ 0.05).