Study of islet cell autoantibodies in serum of siblings of type 1 diabetics

Type 1 diabetes is an autoimmune disease that accounts for approximately 15% of the diabetic population. The pathogenesis of Type 1 diabetes could be divided into six stages. Stage I is genetic susceptibility which requires the presence of a triggering event [stage Il] that initiate the development of autoimmunity [stage Ill] which is characterized by lymphocytic infiltration of the islet cells and production of anti-islet autoantibodies e.g. islet cell cytoplasmic autoantibodies [ICCA], insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], and autoantibodies against irisulinoma-associated-2 autoantigen [IA-2A]. In stage IV, there is progressive loss of insulin secretion despite normal blood glucose level. Stage V develops when overt diabetes is first recognized. In stage VI, there is complete beta cell destruction. Since the clinical onset of Type 1 diabetes does not occur until 80-90% of the insulin-producing pancreatic beta cells have been destroyed, this prediabetic stage may last for a long time during which the immunologic disease markers are present and measurable. The present study aimed to determine the prevalence of the islet cell autoantibodies in siblings of type I diabetics for the presence of islet autoantibodies in an attempt to allow the opportunity for prediction and/or the prevention the clinical onset of the disease. 108 healthy siblings of Type 1 diabetic children [group I] and 100 healthy control subjects [group II] of matched age and sex were enrolled in the present study. IAA, GADA, and IA-2A autoantibodies were assayed in serum of all subjects by radioimmunoassay. Eight of the control subjects had autoantibodies in their sera which were of the IAA type only. In siblings of Type 1 diabetic children, the prevalence of GADA seropositivity showed the highest percentage [25%], followed by IAA [14.81%], then IA-2A [2.78%]. There was significant association between the brotherhood to Type 1 diabetic children and the presence of GADA alone [i.e. no concomitance with any other autoantibody], total GADA [GADA alone and in combination with other autoantibodies], and GADA+IAA [P=0.000, 0.000, and 0.018 respectively]. IAA+GADA+IA-2A or for IAA+lA-2A combinations were not detected in sera of siblings of Type 1 diabetic children. None of the siblings of Type 1 diabetics had lA-2A autoantibodies alone in the serum. From the present results it could be concluded that some degree of islet cell autoimmunity might develop in siblings of type 1 diabetic children as evidenced by the significant association between the presence of GADA or GADA+IAA and the brotherhood to type 1 diabetics. The present results also revealed that GADA is the most frequent autoantibody in serum of siblings of type 1 diabetics. They also showed that the presence of GADA per se conferred the highest significant association with the brotherhood to Type I diabetic children. However, a larger prospective study is recommended to ascertain the importance of the assay of these immunologic markers for the prediction and possible prevention of type 1 diabetes in individuals at risk e.g. sibling, parents, and offspring of Type 1 diabetics

Study of serum zinc, copper, magnesium, postassium and selenium in relation to serum Autoantibodies in siblings of type 1 diabetics

Aim: This work was intended to study the state of some elements namely zinc, copper, magnesium, potassium and selenium in sera of siblings of type 1 diabetic patients and its possible relation to some immunological markers. Subjects and The study included 208 subjects classified into 2 groups: group I included 108 siblings of type 1 diabetic patients and group II included 100 control subjects matched for age and sex. All subjects were subjected to the following: estimation of fasting and 2 hour postprandial plasma glucose and oral glucose tolerance test when needed. Determination of serum level of zinc, copper, magnesium, potassium and selenium was done using atomic absorption spectrophotometry. Measurement of serum insulin autoantibodies [IAA], antibodies to the protein tyrosine phosphatase-like proteins ICA512 [IA-2] and glutamic acid decarboxylase antibodies [GADA] was performed using radioimmunoassay [RIA] technique. The mean serum levels of zinc and copper were significantly higher [P = 0.000 for each], and the mean serum levels of selenium and potassium were significantly lower [P = 0.002 and 0.007, respectively] in type 1 diabetic siblings when compared with control subjects. Zinc and copper were significantly higher [P = 0.000 for each], and magnesium was significantly lower [P = 0.001] in the sera of siblings positive for IAA as compared to the seronegative cases. Selenium was found to be significantly lower in the sera of siblings positive for IAA, IA2 and GADA when compared to the seronegative cases [P = 0.000 for each]. Our results point to a disturbance in the serum levels of zinc, copper, selenium, potassium and magnesium. These nutritional elements may contribute as an environmental factor, that in conjunction with genetic factors, triggers the immunopathogenic sequence responsible, preceding and/or associated with beta cell damage in type 1 diabetes or its complications

Ultrastructural study of aorta in and changes induced by schistosomiasis mansoni

The aim of the present work has been to study the ultrastructural details of the mice aorta and changes induced by a challenge infection with Schistosoma mansoni. For that, 50 male mice were infected by the tail immersion method and sacrified six weeks after-infection. The electron microscopic study of the mice Aorta revealed an intima formed of endothelial cells, a media formed of well developed parallel dense elastic laminae, containing in between smooth muscle fibre cells, and an adventitia formed mostly of collagenic fibrils. Schistosomiasis led to endothelial hypertrophy and degenerationjsubendothelial proliferation containing collagenic fibrils, cellular debris and migrating degenerated smooth muscle fibres, splitting of elastic laminae of media and their fragmentation into islands, degeneration of smooth muscle fibres of the media with enlarged mitochondria and vacuolation of their cytoplasm, and fibrosis encroaching and surrounding most of the structure of the vessels. These changes have been related to the toxic and/or antigenic activity of the parasite since only present in infected animals. Besides, experimental schistosomiasis in the present work was not associated with other infections, metabolic or dietary factors, farther consolidating the view of the deleterious effect of schistosomiasis mansoni per se on the arterial blood vessels. These ultrastructural changes in mice Aorta induced by schistosomiasis mansoni we described for the first time in such an experimental design