Markers of acute neuropsychiatric systemic lupus erythematosus: a multidisciplinary evaluation.

This study was aimed to assess: (1) the additive diagnostic utility of diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) over conventional MRI in detecting brain lesions in patients with acute primary neuropsychiatric systemic lupus erythematosus (NPSLE), and (2) the relevance of their findings to the associated NP manifestations. Included were 34 patients with acute NPSLE with mean age of 33.26 ± 10.14 years and duration of illness of 3.33 ± 1.71 years. Clinical interviewing and psychiatric and cognitive evaluations were performed by applying the criteria of the diagnostic and statistical manual of mental health disorders criteria (DSM-IV), Stanford Binet Subset Testing, Mini-Mental State Examination and Wechsler Memory Scale-Revised. Serologic tests included looking for antinuclear antibodies, anti-double strand DNA, anti-phospholipid antibodies. Radiologic evaluation included conventional MRI, DWI and MRA. One or more NP manifestations were diagnosed in 28 patients, in which cognitive deficits were reported with headache, psychosis and CVS. Anti-phospholipid antibodies were reported in patients with CVS. Twenty patients (71.43 %) with primary NPSLE (n = 28) had MRI abnormalities in which hyperintense signals at subcortical and periventricular white matter and at the junction between the gray and white matter represented 75 % (n = 15) and with headache (n = 6), psychosis (n = 6) and acute confusional state (n = 3) with and without cognitive deficits, respectively. Moderate-sized infarctions with restricted diffusion in the distribution of middle cerebral arteries were represented in 35 % (n = 7) and with CVS, of them, 71.43 % (n = 5) had beading and focal narrowing of carotid arteries were consistent with vasculitis. Brain atrophy represented 20 % (n = 4) and with psychosis. Compared to those with normal MRI, patients with MRI abnormalities were older (P < 0.050) and had longer duration of illness (P < 0.050). To conclude, although DWI and MRA are helping in more precise etiopathologic diagnosis compared to conventional MRI, but their relevance to the present NP manifestations is still limited.

Does herpes simplex virus have a role in the pathogenesis of systemic lupus erythematosus in Egyptians?

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune mediated tissue damage affecting a wide range of organs. The pathogenesis of SLE is complex. Infectious agents, including viruses, can act as environmental triggers, inducing or promoting onset and exacerbations of autoimmune disease in genetically predisposed individuals. Viral infections may be involved in the pathogenesis of SLE. To date, there is no published data about role of herpes simplex virus (HSV) in pathogenesis of SLE in Egyptian population. This study was designed to investigate a possible role of HSV in pathogenesis of SLE and its relation to disease activity. This study included 90 SLE female patients and 83 apparently healthy age-matched female subjects. SLE disease activity was assessed using SLEDAI-2K score. Qualitative assessment of anti-HSV antibodies (HSV1/2 IgM and IgG) was performed using ELISA kits. There was no statistically significant difference in frequency of HSV1/2 IgG positive test between SLE patients (97.6%) and control subjects (94.4%). There was a statistically significant increase in frequency of HSV1/2 IgM positive test in SLE patients compared to control subjects (P < 0.001). There was no difference in the frequency of HSV1/2 IgM and HSV1/2 IgG positive test results between SLE patients with higher disease activity score (60% and 95.6%, respectively) and those with lower disease activity score (60% and 93.3%, respectively). High prevalence of HSV1/2 IgG antibodies was observed among Egyptians. The lack of significant difference in frequency of HSV1/2 IgG between SLE patients and control subjects may indicate that HSV is not involved in SLE pathogenesis. Also, HSV infection may have no role in SLE disease exacerbation due to the absence of significant difference in the frequency of HSV1/2 IgM and HSV1/2 IgG antibodies in SLE patients with higher disease activity compared to those with lower disease activity.

Single nucleotide polymorphism T869C of transforming growth factor-beta 1 gene and systemic lupus erythematosus: association with disease susceptibility and lupus nephritis.

Transforming growth factor ß1 (TGF-ß1) has a large role in the control of autoimmunity. Single nucleotide polymorphisms (SNP) in the promoter of TGF-ß1 cytokine gene are known to alter the production of this important cytokine. Decreased levels of TGF-ß1 may contribute to systemic lupus erythematosus (SLE) susceptibility, activity and organ damage. Lupus nephritis (LN) occurs in more than one-third of patients with SLE. In this study we measured serum levels of TGF-ß1 and assessed TGF-ß1 single nucloetide polymorphism (SNP) at codon 10 (T869C) in Egyptian SLE population in order to verify whether there is a relationship between this polymorphism, serum level of TGF-ß1, SLE susceptibility, clinical manifestations and lupus nephritis. We studied 56 consecutive SLE female patients and 40 healthy female volunteers as control group. Serum levels of TGF-ß1 were measured by enzyme-linked immunosorbent assay (ELISA) and the polymorphism of the TGF-ß1 gene, T869C was analyzed using the method of amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The genotype and allele frequencies of T869C of the TGF-ß1 gene did not differ between SLE patients and healthy controls. Serum levels of TGF-ß1 were significantly reduced in patients with SLE as compared with levels in healthy controls (P < 0.001). The genotype and allele frequencies of T869C of the TGF-ß1 gene did not differ between SLE patients with lupus nephritis (LN) and SLE patients without LN. Lower levels of TGF-ß1 were found in patients with LN than in patients without LN. TGF-ß1 was significantly decreased in TT group than in CC and TC groups (P < 0.001). No significant correlation was found between serum TGF-ß1 level, SLEDAI scores and clinical manifestations. In conclusion, these results suggest that T869C polymorphism of the TGF-ß1 gene is not associated with SLE disease susceptibility and specific clinical manifestations. However, this polymorphism may lead to the production of low serum level of TGF-ß1 especially with TT genotype and consequently plays an important role in the development of renal damage.

Evaluation of transforming growth factor alpha and vascular endothelial growth factor in diagnosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors. It is important to detect disease and recurrence at its earlier period. We aimed to evaluate the usefulness of TGF-alpha and VEGF in diagnosis of HCC patients. Thirty patients with liver cirrhosis, 30 patients with confirmed HCC and 20 healthy volunteers were subjected to abdominal ultrasonography, and alpha-fetoprotein, TGF-alpha and VEGF were assessed. Serum level of AFP was significantly higher in HCC than cirrhotic patients and controls and in cirrhosis patients than controls. The level of TGF-alpha was significantly increased in HCC and cirrhosis groups than in control group with no difference between cirrhosis and HCC groups. Serum VEGF was higher in HCC than in cirrhosis group and in both groups than in control group. Sensitivity and specificity of makers in diagnosis of HCC were 63%, 90% respectively for AFP using a cutoff value of 19.96 ng/ml; 60% and 92% for VEGF at cut off 268 and 73% and 84 % for TGF-alpha using a cutoff value of 13.95 pg/ml. VEGF may be useful serum marker for detection of HCC in addition to traditional markers.

Mannose binding lectin gene polymorphism and preclinical carotid atherosclerosis in patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have increased risk of atherosclerosis and CVD that cannot be explained by traditional risk factors. Previous studies indicated that mannose binding lectin (MBL) may modify the development of atherosclerosis. This study was designed to investigate association of MBL gene polymorphism with occurrence of preclinical atherosclerosis in SLE. The study included 46 patients with SLE and 17 age and sex matched controls. MBL2 genotypes were assessed in patients and controls by the PCR-RFLP method and intima-media thickness of the common carotid artery (cclMT) was determined by means of ultrasonography. Also, serological markers were measured and the disease activity index (SLEDAI) was estimated. SLE patients had higher frequency of MBL A/B + B/B genotypes (47.8%) than controls (29.4%). ccIMT was higher in patients having A/B, B/B, A/B+B/B genotypes when compared with wild genotype (A/A). Patients with A/B+B/B genotypes showed high serum level of LDL, TG, ESRI, CRP and SLEDAI score, but low level of HDL, C3, and C4 compared to wild genotype. ccIMT of mutant SLE subgroup correlated well with SLE risk factors for atherosclerosis. In conclusion, mutant genotypes of MBL may be atherogenic as SLE patients had a higher IMT, which correlated significantly with SLE risk factors for atherosclerosis.

Value of serum and synovial fluid activin A and inhibin A in some rheumatic diseases.

AIM: The purpose of the study is to measure serum and synovial fluid levels of activin A and inhibin A in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and osteoarthritis (OA) and correlate them with disease activity parameters. SUBJECTS AND METHODS: This study included 60 patients with various rheumatic diseases (20 with RA, 20 with SLE and 20 with OA), as well as 10 healthy controls. All of them were subjected to complete history-taking, examination and estimation of disease activity index. The following investigations were done for all subjects: serum and synovial activin A, inhibin A, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-dsDNA and complements 3 and 4. RESULTS: Serum levels of activin A were significantly higher in RA, SLE and OA than controls and in RA and SLE versus OA The mean values of serum inhibin A were significantly higher in all studied groups than controls. Synovial activin A and inhibin A were significantly higher in RA than OA. Positive correlations were found between serum activin A and disease activity parameters of RA. In SLE, positive correlations were found between serum activin A and inhibin A with ESR and SLE Disease Activity Index. CONCLUSIONS: Serum activin A and inhibin A were significantly higher in RA and SLE. Serum levels correlated positively with disease activity parameters of RA and SLE. However, synovial levels were significantly higher in RA than OA but showed no correlation or negative correlation with disease activity. We recommend further studies to detect the exact role of activin A and inhibin A in these conditions.