Decreased level of soluble receptors of advanced glycated end products [sRAGE] and Glycine 82 Serine [G82S] polymorphism in patients with RA

The receptor for advanced glycated end products [RAGE] is a multi-ligand receptor expressed as a cell surface molecule, interacting with diverse ligands. Since soluble RAGE [sRAGE] acts as a competitive receptor for cellular RAGE, the balance between these two types of receptors might be of importance in the pathogenesis of RA. To evaluate the levels of sRAGE in patients with RA compared with healthy controls and to assess the relationship between sRAGE levels and disease characteristics. Also, we assessed the association between the gene variants and the sRAGE level and disease activity. The study included 33 patients with RA and 16 healthy normal controls. All patients and controls are subjected to full clinical assessment, joint examination including tender joint count [TJC], swollen joint count [STC] and estimation of DAS 28 and laboratory investigations including CBC, ESR, urine analysis, kidney function tests, liver function tests, RF and C-reactive protein [CRP]. Soluble RAGE was determined by enzymatic immunoassay and molecular study was done for single nucleotide polymorphisms [SNP] in the glycine 82 serine [G82S] of the RAGE gene. RF was positive in 72.7% of patients and was negative in all controls. CRP was significantly higher in RA patients as compared with controls [p < 0.01]. Serum levels of sRAGE were significantly lower in RA patients than controls. RA: Rheumatoid arthritis. AGEs: Advanced glycation endproducts. sRAGE: Soluble receptor for advanced glycation end products. NF-KB: Nuclear factor-kappaB. DAS28: Disease activity score. MS: Morning stiffness. TJC: Tender joint count. SJC: Swollen joint count. CRP: C-reactive protein. SNP: Single nucleotide polymorphisms. G82S: Glycine 82 serine gene polymorphism. HMGB1: High mobility group box I or amphoterin. MMPs: Matrix metalloproteinases. [840.11 +/- 230.32 versus 1111.59 +/- 143.20, p < 0.05]. Genotyping of the RAGE gene showed G82S in 22 out of 33 RA patients, 5 of them were homozygous for the RAGE serine 82 allele, while genotyping in the control subjects showed polymorphisms in the G82S in 5 out of 16, only one of them was homozygous for the RAGE G82S allele, indicating significantly increased G82S allele in RA patients as compared with controls [p < 0.05]. The G82S allele was related to the MS, CRP and sRAGE in RA patients. The sRAGE levels were significantly lower in RA patients with more disease activity as indicated by MS, TJC and CRP. The sRAGE levels were significantly lower in RA patients with cardiac disease than those without cardiac disease. Linear regression analysis detected CRP and gene polymorphism as significant predictors for sRAGE. The levels of sRAGE were significantly lower in patients with RA and this reduction was correlated with the disease activity and glycine 82 serine gene polymorphism. Thus, the sRAGE may be an important marker of disease activity and can be used as a therapeutic target in these conditions

Correlation between level of soluble receptors of advanced glycated end products [sRAGE] and gene polymorphism of glycine 82 serine [G82S] in patients with rheumatoid arthritis

The receptor for advanced glycated end products [RAGE] is a multi-ligand receptor expressed as a cell surface molecule, interacting with diverse ligands. Since soluble RAGE [sRAGE] acts as a competitive receptor for cellular RAGE, the balance between these two types of receptors might be of importance in the pathogenesis of RA. To evaluate the levels of sRAGE in patients with RA compared with healthy controls and to assess the relationship between sRAGE levels and disease characteristics. Also, we assessed the association between the gene variants and the sRAGE level and disease activity. The study included 33 patients with RA and 16 healthy normal controls. All patients and controls are subjected to laboratory investigations including CBC, ESR, urine analysis, kidney function tests, liver function tests, RF and C-reactive protein [CRP]. Soluble RAGE was determined by enzymatic immunoassay and molecular study was done for single nucleotide polymorphisms [SNP] in the glycine 82 serine [G82S] of the RAGE gene. RF was positive in 72.7% of patients and was negative in all controls. CRP was significantly higher in RA patients as compared with controls [p<0.01]. Serum levels of sRAGE were significantly lower in RA patients than controls [840.11 +/- 230.32 versus 1111.59 +/- 143.20, p<0.05]. Genotyping of the RAGE gene showed G82S in 22 out of 33 RA patients, 5 of them were homozygous for the RAGE serine82 allele, while genotyping in the control subjects showed polymorphisms in the G82S in 5 out of 16, only one of them was homozygous for the RAGE G82S allele, indicating significantly increased G82S allele in RA patients as compared with controls [p<0.05]. The G82S allele was related to the CRP and sRAGE in RA patients. The sRAGE levels were significantly lower in RA patients. Linear regression analysis detected CRP and gene polymorphism as significant predictors for sRAGE. The levels of sRAGE were significantly lower in patients with RA and this reduction was correlated with the disease activity and glycine 82 serine gene polymorphism. Thus, the sRAGE may be an important marker of disease activity and can be used as a therapeutic target in these conditions

Serum interleukin levels in asthmatic patients with eosinophilia

The incidence, morbidity and mortality of bronchial asthma have increased over the last two decades. Immune and inflammatory responses mediated by cytokines are essential in the pathophysiology of bronchial asthma. Substantial evidence has implicated Th2 cytokines, IL-4 and IL-5, in the pathology of allergic asthma and demonstrated protective effects of Th1 cells. This work was conducted to study the serum levels of IL-4, IL-5, IL-12 and IL-18, in patients with allergic asthma associated with eosinophilia. Interleukins levels were correlated with IgE level and the degree of eosinophilia in these patients. The study included 25 asthmatic patients with acute attack of bronchial asthma, associated with history of allergy and eosinophilia; and 25 normal healthy controls. All patients and controls were subjected to full medical history, clinical examination, and laboratory investigations for assessment of the eosinophil count and measurement of serum levels of IgE and interleukins [IL-4, IL-5, IL-12 and IL-18]. The correlation between interleukin [IL] levels, and degree of eosinophilia and IgE levels were also examined in these patients. Measurement of serum levels of interleukins showed significant elevation of IL-4, IL-5 and IL-18 levels in asthmatic patients as compared with the control group [p<0.0001], whereas IL-12 levels did not show any significant change [p>0.05]. Marked elevation in the IgE level and eosinophil count were also detected in asthmatic patients as compared with the control group [p<0.0001]. Significant positive correlations were observed between serum levels of IL-4, IL-5 and IL-18 and the degree of eosinophilia in asthmatic patients. A significant positive correlation was also detected between level of IL-18 and the IgE level in asthmatic patients. Patients with allergic bronchial asthma have elevated levels of IL-4, IL-5 as well as IL-18; and these levels correlated significantly with degree of eosinophilia in these patients. Further studies are needed to clarify the signaling cascade involved in allergic responses mediated by these ILs. This may help in developing new therapeutic modalities, as blockade of IL receptors, for these conditions

Cardiac involvement in primary antiphospholipid syndrome and anticardiolipin positive systemic lupus erythematosus

Since the recognition of antiphospholipid syndrome [APS], many cardiac manifestations have been reported in association with the anti-phospholipid [aPL] antibodies. The APS syndrome can be either primary or secondary to an underlying condition, most commonly systemic lupus erythematosus [SLE]. Echocardiographic studies have disclosed heart valve abnormalities in about a third of patients with APS. The aPL antibodies have been suggested to be a pathogenetic factor in the cardiac abnormalities. To evaluate prospectively the prevalence of cardiac abnormalities in patients with SLE and primary antiphospholipid syndrome [PAPS], and correlate these data with serum level of anticardiolipin [aCL] antibodies. Sixty three patients with SLE [62 females and 1 male] were enrolled and divided into two groups according to the presence [Group III, n=35] or absence of aCL [Group II, n=28]. Ten patients with PAPS [7 females and 3 males] were recruited [Group IV, n=10]. In addition, 23 healthy age and sex matched controls, were included [Group I] The serum levels of IgG and IgM aCL antibodies were measured for all patients and controls by a st and ardized ELISA test. All patients and controls also, underwent st and ard two-dimensional and Doppler echocardiographic examination within a week of serum testing. The aCL IgG antibodies were positive in 30 of 63 [47.6%] patients with SLE, in all 10 [100%] patients with PAPS, and in 1 of 23 [4.5%] control individuals. The aCL IgM antibodies were positive in 12 of 63 [19%] patients with SLE, in 4 of 10 [40%] patients with PAPS, and in none of the control individuals. Both IgG and IgM aCL antibodies were positive in 7 of 63 [11%] patients with SLE and in 4 of 10 [40%] patients with PAPS. Echocardiographic findings showed normal heart in all control subjects [group I], and in 16 [57%] of SLE patients with absence of elevated aCL levels [group II], 10 [28.5%] of SLE patients with elevated aCL levels [group III] and 3 [30%] of patients with PAPS [group IV]. Valvular lesions were detected in 7 patients [25%] in group II, 15 [43%] in group III and 7 [70%] in group IV. Pericardial effusion was SLE: systemic lupus erythematosus, PAPS:primary antiphospholipid syndrome, aPL:anti-phospholipid antibodies, aCL:anticardiolipin antibodies. detected in 3 patients [11%] in group II, 10 [28.5%] in group III, and 1 [10%] in group IV. Myocardial dysfunction was detected in 1 patient [3.5%] in group II, 7 [20%] in group III and 2 [20%] in group IV Left ventricular hypertrophy was detected in 2 patients [7%] in group II, 5 [14%] in group III and 1 [10%] in group IV. Pulmonary hypertension was detected in none [0%] of patients in group II, 4 [11.5%] in group III and 2 [20%] in group IV Diastolic dysfunction was detected in 12 patients [43%] in group II, 14 [40%] in group III and 4 [40%] in group IV. Valvular lesions, myocardial dysfunction and pulmonary hypertension in patients with PAPS and SLE are associated with elevated aCL antibodies. There was no significant difference in the frequency of cardiac involvement between patients with increased aCL antibodies in SLE and those with PAPS. Thus, aCL may play an important role in the pathogenesis of valvular lesions as well as myocardial abnormalities