Echocardiographic abnormalities and anticardiolipin antibodies in Egyptian patients with systemic lupus erythematosus

Systemic lupus erythematosus [SLE] is an inflammatory disease characterized by deposition of autoantibodies and pathogenic immune complexes in cells and tissues causing lesions. Cardiac involvement in patients with SLE has been described since the early 20th century. Echo-cardiography is time main instrument for investigating the anatomical and functional involvement of the heart in the great majority of systemic diseases. Antiphospholipid syndrome is an autoimmune disease characterized by antiphospholipid antibodies and at least one clinical manifestation, the most common being venous or arterial thrombosis and recurrent fetal loss. Anticardiolipin IgG antibodies have been linked to several cardiac manifestations in patients with SLE. -to study the cardiac abnormalities in Egyptian patients with SLE, to determine its relation to other clinical features of SLE and its association with anticardiolipin antibodies [IgG]. This study involved thirty patients with SLE. Patients were classified into two groups according to having any abnormal finding on echocardiography into Echo positive patients [23 patients] and echo negative patients [7 patients]. Patients were also classified into two groups according to ACL IgG seropositivity into Group I: ACL positive patients [18 patients] and Group II. ACL negative patients [12 patients]. Group I with ACL +ve were further classified according to ACL titer of antibodies into: Group IA: with high titer [10 patients] and Group IB: with low titer [8 patients]. The study involved also a control group of 15 age and sex matched apparently healthy individuals. For each one detection of anticardiolipin antibodies IgG, transthoracic echocardiography in addition to liver and renal function tests were done. Results were subjected for statistical analysis. This study revealed that cardiac involvement in SLE is very common and it is not related to other clinical features of lupus, age, disease duration or to activity of disease. 23 patients had echocardiographic abnormalities [76.60%], 11 patients had pericardial effusion [36.60%], 1 patient had LV diastolic dysfunction [3.3%], 3 patients had LV systolic dysfunction [10%], 3 patients had Pulmonary hypertension [10%] and 16 patients had Valvular abnormalities [53.30%]. The valvular abnormalities were affecting the mitral valve in 16 patients [53.3%], aortic valve in 2 patients [6.6%] and tricuspid valve in 7 patients [23.3%]. No pulmonary valve affection was detected. Valvular involvement - especially regurgitation and thickening of the mitral valve - is the most encountered forum of heart disease in SLE followed by pericardial effusion. Comparative study between anticardiolipin positive and negative groups regarding echocardiographic abnormalities showed no statistical significance [P > 0.05]. ACL shows a tendency towards a statistical significance with MV thickening [P = 0.06]. Comparative study between patients of ACL +ve SLE patients according to titer of anticardiolipin antibodies IgG revealed statistically significant difference between both groups as regards BUN, PTT creatinine clearance, SLAM score and number of valve regurgitation in each patient [P < 0.05] as well as echo abnormalities in general [P < 0.05]. Cardiac involvement in SLE specially valvular affection followed by pericardial effusion - is very common although, clinical involvement is not very common and it is not related to other clinical features of lupus. ACL IgG antibodies play a role in the pathogenesis of the severity of cardiac affection in general and valvular lesions in particular and in time pathogenesis of lupus nephropathy

Autoimmunity and predictors of autoimmune diseases in the first degree relatives of patients with primary biliary cirrhosis

Primary biliary cirrhosis [PBC] is a chronic autoimmune disease of unknown cause that leads to destruction of intrahepatic ducts leading to ductopenia, fibrosis and ultimate biliary cirrhosis. Autoimmunity and autoimmune diseases were reported in family members of PBC patients. The aim of the present study was to investigate the prevalence of biochemical and immunological abnormalities and autoimmune diseases in first degree relatives [FDR] of patients with PBC. This study included: [1] A female [45 years old] patient diagnosed as having PBC, [2] Five FDR [3 females and 2 males] and [3] Fifteen blood donors [3 females and 12 males] were taken as a control group. Blood samples were taken from all subjects for the detection of nitric oxide [NO], transaminases [AST and ALT], alkaline phosphatase [ALP], total protein and albumin by colorimetric methods. Indirect immunofluorescent techniques were used for the detection of anti-nuclear antibodies [ANA], anti-smooth muscle antibodies [ASMA], anti-actin antibodies [AAA], anti-liver/kidney microsomes antibodies [LKM-I] and anti-mitochondrial antibodies [AMA]. Serum IgM was detected by radial immunodiffusion. Anti-SSA, anti-SSB and IgM rheumatoid factor [IgM RF] were detected by enzyme linked immunosorbent assays. Our PBC patient had a marked increase serum ALP level and a mild elevation in transminases. After treatment, serum ALP level dropped markedly [but still elevated] while the transaminases did not show a remarkable change. A marked elevation was noted in the serum levels of total globulins before and after treatment. A detectable decrease in the level of serum IgM was found after treatment. NO level of our patient was elevated [7 micro moI/L] at presentation while after treatment the level of NO returned to the normal level. AMA titer of our patient was 1/20 which considered a low titer. ANA titer was the same [1/40] before and after treatment. HCV antibodies, HBsAgs and other autoantibodies were absent before and after treatment. The titer of ASMA dropped from 1/160 to 1/40 after treatment. The pattern of these ASMA was the Vessels [V] pattern. In the FDR, the level of NO was elevated in sister-2, son-1 and the daughter. The AST ALT, ALP, total protein and albumin were normal in all subjects. Serum total globulins and IgM were elevated in sister-1, sister -2 and son-1. The ANA titer was 1/40 with a speckled pattern in all FDR. AAA, anti-SSA, anti-SSB, AMA, HBs Ag were negative in all FDR with the exception of sister-2 while had a positive anti-SSB. The ASMA were positive with the same pattern with varying titers. HCV antibodies were positive only in son-1 while was also the only FDR- to have autoantibodies to LKM-1. Sister-1 and sister-2 were diagnosed as a seropositive rheumatoid arthritis [RA] about 2 and 2.5 years after the development of PBC in our patient. The 15 blood donors showed a normal results except subjects 6 and 11 who had ASMA with a titer of 1/20 and subject 7 who had a positive ANA [titer l/40]. An autoimmune disease [RA] developed in two sisters of the PBC patient. Predictors of autoimmune diseases like elevated NO, LKM-1 and SSB antibodies are common in the FDR of a patient with PBC. Follow up of such subjects with these autoimmune predictors is recommended

Anti cyclic citrullinated peptide antibodies in IgM rheumatoid factor positive patients: a new insight

The presence of IgM rheumatoid factor [IgM RF] is one of the clinical criteria for the diagnosis of rheumatoid arthritis [RA]. The cutoff point of IgM RF assays is usually based on a reference level obtained from normal subjects in the same population as the patients. However, raising the cutoff values increases the specificity of RF testing. The present study was undertaken to investigate this observation with the help of anti cyclic citrullinated peptide [CCP] antibodies to be of potential diagnostic value. Seventy six patients were chosen with arthritis and IgM RF titers > 20 units/ml. Subsequently, patients were classified according to their IgM RF titers: patients with titers 40 units/ml [group B] and patients [selected from group B] with titers >120 units/ml [group C]. Twenty one RA patients with IgM RF negative and positive anti CCP antibodies were also included in this study. In all serum samples, IgM RF, anti CCP, hepatitis C virus antibodies [HCV], anti-Smith and anti-ribonucleoprotein [anti-RNP] antibodies were determined by ELISA. PCR analysis was performed for all patients with positive HCV antibodies. Antinuclear antibodies [ANA] and anti-dsDNA were determined by indirect immunofluorescence. In patients of groups A, B and C, RA was detected in 28.6, 80.5 and 83.3% of all patients, respectively. Anti CCP antibodies detected RA in 22.85, 75.6 and 77.8% of all patients in groups A, B and C, respectively. IgM RF positive non RA patients were diagnosed in 71.4, 19.5 and 16.7% among all patients included in group A, B and C, respectively. In group A, anti CCP antibodies correctly classified 24/25 [96%] of patients with false positive IgM RF as non RA patients, they were positive in only one patient with rhupus. Anti CCP antibodies were positive in 2.8, 4.9 and 11.1% in non RA patients among all patients in group A, B and C, respectively. Anti CCP antibodies were present in 80, 93.9 and 93.3% of RA patients in groups A, B and C, respectively. The overall presence of anti CCP in seropositive RA patients was 90.6%. Kappa statistics showed an excellent agreement between IgM RF and anti CCP for the serodiagnosis of RA. Among the non RA patients of group A, it was found that 9/25 [36%] of patients diagnosed as having HCV infection. Anti CCP antibodies were negative in all HCV patients. Low positive titers of anti CCP antibodies were more prevalent [76.2%] in patients with seronegative RA than in patients with seropositive RA [17.9%]. Results demonstrated that: [1] anti CCP antibodies correctly classified about 24/25 [96%] of patients with false positive IgM RF [< 40 units/ml] as non RA, [2] high titers of IgM RF [>120 units/ml] are of similar high specificity to anti CCP antibodies and [3] anti CCP antibodies are able to differentiate between patients with HCV infection associated with arthritis and patients with RA

possible protective role of lisinopril as a pro-apoptotic agent in cyclosporin A induced nephrotoxicity in rats

The study was carried out on 40 male albino rats, which were divided into five groups: Group 1, normal control group, group 2, saline treated group, group 3, cyclosporin A treated group [rats received saline 0.2 ml for one week orally daily, then received cyclosporin A [20 mg/kg/day] intraperitoneally daily for another week], group 4, lisinopril plus cyclosporin A treated group [treatment with lisinopril [10 mg/kg/day] orally for one week, then co-administration, of both lisinopril and cyclosporin A for another one week using the aforementioned doses] and group 5, lisinopril-treated group [rats received lisinopril [10 mg/kg/day] orally for two weeks]. At the end of the study, blood samples were withdrawn from rats of all groups for determination of serum creatinine. Afterwards, rats were sacrificed and the kidneys were obtained. Sections from the kidney were stained by hematoxylin and oesin and immunohistochemically using anti-Bcl-2 antibodies for assessment of both necrosis and apoptosis, respectively. Cyclosporin A administration for one week significantly raised the serum creatinine level. Also, it produced histopathological changes confined to the proximal convoluted tubules in the form of moderate to severe focal necrosis, and produced strong Bcl-2 cytoplasm immunostaining. Treatment with lisinopril for one week, then co-administration, of both lisinopril and cyclosporin A, decreased significantly the cyclosporin A-induced elevation of serum creatinine, decreased the focal necrosis in the proximal convoluted tubules [Chi square=13.3], and produced weak Bcl-2 cytoplasm immunostaining [Chi square=7.27]. This denotes that the ACE inhibitor ameliorated the toxic insult induced by CsA by favoring induction of apoptosis as denoted by diminishing the Rcl-2 cytoplasmnostaining. From the above data, it could be concluded that lisinopril has a proapoptotic effect in the kidney after cyclosporin A-induced nephrotoxicity