Ophthalmic disorder in patients with latent autoimmune diabetes in adult

It is well known that about 90% of all cases of diabetes mellitus [DM] are type 2, which is characteristic for adults aged above 40 years. Ten percent is represented by type 1 DM, typical for children and young. Adult's onset diabetes represent a heterogeneous mixture of type 1 and type 2 DM, often difficult to differentiate between, those patients may have actually latent autoimmune diabetes in adults [LADAs], where beta-cell destruction is less aggressive, leading to a slower development of insulin dependency. Studies indicated that antibodies against glutamic acid decarboxylase 65 [GAD 65] are good marker for diagnosis of autoimmune diabetes in adults who are not responding to oral hypoglycemic and may be at risk for getting complications namely increased risk of diabetic retinopathy. GAD 65 is mainly expressed in beta-cells of Langerhans but also in nonbeta-cells. GAD is an enzyme required for gama-aminobutyric acid [GABA] synthesis that acts as neurotransmitter in neurons of central nervous system and in pancreatic islets. GABA is probably involved in controlling the release of insulin from secretary granules

Determination of antiphospholipid antibodies and Thrombophilia in women with recurrent miscarriage

Recurrent miscarriage is a critical problem in which many factors play a crucial role such as. antiphospholipid antibodies [APA] and anticardiolipin antibodies [ACA]. Recent studies pointed to a potential role of thrombophilias as a possible cause of recurrent miscarriage [RM]. This study was conducted to determine the frequency of the primary and secondary antiphospholipid syndrome and the haemostatic abnormalities in women with history of RM. This study was a case control study, conducted from Febraury-2008 to February -2011 in Khartoum State. A total of 100 women with three or more consecutive recurrent miscarriage without previous living babies as case group and 100 non complicated pregnant women were screened for the presence of antinuclear antibodies [ANA], anti-double stranded DNA [anti-dsDNA], antiphospholipid antibodies [APA IgM/IgG], and anticardiolipin antibodies [ACA/IgG] by using Enzyme Linked Immuno-Sorbent Assay [ELISA]. Patients with history of three miscarriages with delivery of full-term or preterm babies in between or with medical termination of pregnancy were excluded from this study. Women positive for APA were asked for a repeat sample after 6 weeks to run confirmatory test. Patient and control groups were also screened for the count of platelets using Sysmex KXN-21, Activated Partial Thromboplastin Time [APTT], Prothrombin Time [PT] and Thrombin Time [TT] using coagulometer Biobas 10. The frequencies for both APA and ACA were 20%. ANA and Anti-dsDNA were 12%. There was a significant correlation between age and the presence of APA [P=0.03], ACA [IgG] [P=0.04], ANA and Anti-dsDNA [P=0.013]. Frequencies for, thrombocytopenia and lupus anticoagulant [LA] were 8% and 20% respectively. 5% had prolonged PT, whereas the remaining patient and control groups had normal results. The data concluded that the frequencies of APA, ACA, ANA, Anti-dsDNA, in women with RM obtained in this study were in agreement to the frequencies for these parameters obtained in previous studies and their presence were significantly associated with recurrent miscarriage. Frequencies of LA and thrombocytopenia were significantly associated with recurrent miscarriage. Prolongation in PT may be due to the presence of anti-prothrombin antibodies in serum of patients with recurrent miscarriage. The current study recommends measuring of APA, ACA, Anti-dsDNA-antibodies and assessment of platelets count, APTT and PT in all women with recurrent miscarriage and late pregnancy loss

Cytokines as immunological markers for follow up of disease activity during the treatment of pulmonary tuberculosis

Cytokines play a major role in protection against Mycobacterium tuberculosis infection and regulate the immune responses at a cellular level. Cytokine profile determines clinical outcome of the disease and responses to treatment as well. A T helper 1 [Th1] cytokine interferon gamma [IFN-gamma] is one of the most important cytokines which activate the macrophages to produce tumor necrosis factor-alpha [TNF-alpha]. Excessive production of TNF- alpha have been implicated in immunopathogenesis of tuberculosis. A T helper 2 [Th2] response leads to release of IL-4, and IL- 10 promoting an anti-inflammatory macrophage response. Interleukin-4[IL-4], has been implicated to down-regulate IFN-gamma, and thus has a harmful effect on TB patients. IL10 cytokine has the capacity to inhibit Th1 activation and thus terminates cell mediated immune responses. The objective of the present study was to determine Th1 and Th2 cytokine profile in patients with tuberculosis to identify immunological marker for follow up of the disease activity, and to study the outcome of treatment. To examine this, blood samples were collected from newly diagnosed HIV negative pulmonary tuberculosis patients and from apparently healthy individuals as controls following an informed consent. Blood samples were as well collected at several intervals during the treatment with anti-tuberculosis drugs. Levels of IFN-gamma, TNF- alpha, IL-4 and IL-10 were measured pre and during treatment using commercial available enzyme-linked immune-sorbent assay [ELISA]. Data were analyzed using SPSS 20. Receiver Operating Characteristic [ROC] Curve analysis has been carried out to assess their discriminative power and to determine cut-off values. Analysis has been carried out further by calculating other measures of diagnostic test accuracy. The median serum level of IL-4 was 20 and 35 pg/ml higher in new cases [untreated patients] and in patients under treatment with oral anti-tuberculosis, respectively, compared with that of controls [p=001]. Levels of TNF- alpha were significantly increased in patients before and after the treatment than those in control [p=0.001]. New cases had the highest median level [10pg/ml] followed by those under treatment group [6pg/ml]. Levels for IFN-gamma were not statistically different between patients and controls [p=0.351]. Median levels of IL10 were similar in both controls and new cases groups [35pg/ml], but lower in patients under treatment group [20pg/ml]. Increase in levels of IL-4 during treatment showed that Th2 immune responses still present and may indicate active disease and thus IL4 cytokine may be a possible marker for the disease activity. Serum levels of TNF- alpha in TB patients is useful in the evaluation of the disease activity during therapy, not replacing clinical parameters of disease activity in TB. Similar to TNF- alpha, IL-4 can also be used as marker for TB severity. On the other hand IL-4test can be used to diagnose TB in highly exposed suspects where a positive result is more likely to indicate TB

Reliability of Cyclic Citrullinated peptide antibodies [Anti-CCP] for the diagnosis of rheumatoid arthritis as compared to that of rheumatoid factor test

Rheumatoid factor [RF] is commonly used for diagnosis of rheumatoid arthritis [RA]. RF positivity is nonspecific for diagnosis of RA because it can be detected in 3-5% of normal individuals. Recent studies indicated that anti-Cyclic-Citrullinated protein [Anti-CCP] antibodies are more specific to diagnose rheumatoid arthritis and have the capacity to diagnose RA in early stages of the disease, or even before the onset of the disease when the arthritis is undifferentiated. This study has been conducted to assess the reliability and specificity of anti-CCP in Sudanese as an indicator of RA. In this study, patients were diagnosed as RA patients according to the American College of Rheumatology [ACR] criteria. To get further insight on the sensitivity and specificity of Anti-CCP test as compared to that of RF test in the diagnosis of RA, analysis of samples obtained was performed using enzyme linked immune sorbent assay [ELISA] and latex agglutination test. All the results were analyzed using Statistical Packages of Social Sciences [SPSS]. Anti-CCP test achieved higher specificity [86.7% Vs 60%] and sensitivity [74.3% Vs 60%] compared with RF. However, despite that the accuracy of anti-CCP to diagnose RA was high [76.5%], the false negative rate reached 21.2%. Although anti-CCP test is more accurate compared with RF; it may sometimes fail to diagnose some patients with rheumatoid arthritis. However, studies on the predictive values and other conditional ratios for anti-CCP antibodies were scarce

Diagnostic value of autoantibodies to GAD65 and IA-2 in patients with latent autoimmune diabetes in adult [LADA]

Latent autoimmune diabetes in adults [LADA] accounts for11% of all cases of diabetes and often misdiagnosed as type 2diabetes. LADA resembles type 1diabetes and shares common physiological characteristics of type 1 but it does not affect children and has been classified distinctly as being separate from juvenile diabetes. Autoantibodies against glutamic acid decarboxylase 65 [GADA] and tyrosine phosphatase [IA-2] are found frequently in patients with LADA. The presence of these autoantibodies in LADA predicts inevitable cell failure and poor response to oral hypoglycemic therapy i.e., patients with LADA do not respond to oral hypoglycemic therapy. To determine an immunological marker to diagnose patients not responding to oral hypoglycemic therapy. Patients and A facility-based cross sectional study was conducted in Jabbir Abu Eliz Diabetes Center, located at Khartoum 2. Venous blood samples were obtained from the study patients. They were divided into three groups, group1 included 27 diabetic patients treated with insulin, group2 included 15 diabetic patients of type 2 diabetes as controls, and group3 included 15 newly diagnosed patients older than 35 years at onset of diabetes. A standardized pre-tested administered questionnaire was used for data collection and the collected data were analyzed. Males encountered in the study were 28 [49.1%]. On patient recently diagnosed to have type 2 diabetes mellitus [T2DM] was positive for autoantibodies to GDA/IA-2. These autoantibodies were also positive in 15 patients with diabetes mellitus type 1 [T1DM] Autoimmune diagnostics is of particular importance in adults to discriminate between type 1 and type 2 diabetes and to assess the diagnosis of latent autoimmune diabetes in adults. The current study results revealed that autoantibodies to GAD/IA-2 are good marker for diagnosis of latent onset DM type 1. On the other hand, data indicate that the vast majority of cases of type 1 diabetes may be considered as immune-mediated, that multiple autoantibody to GAD/IA-2 analysis are of prognostic value to predict complications e.g., retinopathy. The current study recommends using of anti-GAD/IA-2 antibodies as marker for diagnosis of latent autoimmune diabetes in adults [LADA] who are not responding to oral hypoglycemic and may be at risk for getting complications. On the other hand, the study recommends using of anti-GAD/IA-2 antibodies for prognosis of the clinical progression of diabetes type 1 for prediction of insulin dependence