Receptors, antibodies, and disease.

1984 ◽  
Vol 30 (7) ◽  
pp. 1137-1156 ◽  
Author(s):  
M Blecher
Keyword(s):  
Autoimmune Diseases ◽  
Clinical Symptoms ◽  
Type I Diabetes ◽  
Neurological Diseases ◽  
Clinical Signs ◽  
Connective Tissue Diseases ◽  
Chronic Atrophic Gastritis ◽  
Point Of View ◽  
Type I ◽  
Potential Marker

Abstract Abnormal antibody production is now recognized as the basis of specific endocrine and neurological diseases and their complications. Among the autoimmune diseases, the best understood from a mechanistic point of view are myasthenia gravis, Graves' disease, several variants of insulin resistance, and a variant of bronchial asthma. In each of these human disorders, the clinical symptoms can be traced to the actions of antireceptor antibodies produced by a deranged immune system. The autoantibodies produced in these diseases are functionally heterogeneous. They may produce the clinical symptoms of hormone or neurotransmitter insufficiency either by blocking the binding of these agents to target cell surface receptors or by accelerating the internalization and degradation of these receptors. In other cases, the autoantibodies may produce the clinical signs of hormone excess by mimicking the actions of the hormone, in an uncontrollable fashion. In some cases, functionally different types of autoantibodies will appear in the same patient at different stages of the disease. For all of these autoantibodies, of whatever function, assays for their presence in serum are available, in forms suitable for clinical chemists, as well as for researchers; these will be described in this review. In addition to the known anti-receptor autoimmune diseases, there are a large number of other autoimmune diseases for which there is fragmentary evidence that their clinical symptoms have an anti-receptor autoantibody etiology. Several examples of this group will be discussed, and assays suitable for establishing the presence of anti-receptor antibodies in the sera of such patients will be provided. The disorders to be considered are: type I diabetes mellitus, chronic atrophic gastritis, autoimmune Addison's disease, autoimmune hypoparathyroidism, type II pseudohypoparathyroidism, resistant ovary syndrome, connective tissue diseases, and the HLA-B8/DR3 antigen haplotype as a potential marker for autoimmune diseases of the anti-receptor type.

A highly sensitive microsphere-based assay for early detection of Type I diabetes

TECHNOLOGY ◽  
2014 ◽  
Vol 02 (03) ◽  
pp. 200-205 ◽  
Author(s):  
Shyam Sundhar Bale ◽  
Gavrielle Price ◽  
Monica Casali ◽  
Nima Saeidi ◽  
Abhinav Bhushan ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Type I Diabetes ◽  
Rolling Circle Amplification ◽  
Limited Range ◽  
Assay Method ◽  
Type I ◽  
Rolling Circle ◽  
Highly Sensitive ◽  
Progression Of Disease ◽  
Time Required

Type 1 Diabetes Mellitus (T1DM) is a T-cell mediated autoimmune disease in which deterioration of insulin producing pancreatic β-cells leads to a state of insulin deficiency. It has been shown that the clinical symptoms of T1DM are preceded by presence of islet cell autoantibodies (ICA) in serum. Radioimmunoassay (RIA) based detection of ICA are the current gold standard for diagnosis of T1DM. While the onset of hyperglycemia is an indicator of onset of T1DM, detection of ICA within the serum is important to differentiate T1DM from ketogenic Type 2 Diabetes (T2D) and Maturity Onset Diabetes of the Young (MODY). Due to their limited range of sensitivity, however, RIA cannot detect ICA at low concentrations in serum which could lead to delay in proper diagnosis and treatment. In addition, the use of radioactive species presents major disadvantages including exposure, waste removal, need for specialized licensed facilities to conduct the tests and the time required for the test (> 24 hours). To overcome these limitations, we have developed a rapid, highly sensitive, fluorescent and microsphere-based assay technique using Rolling Circle Amplification (RCA), to profile T1DM marker antibodies in serum. This assay utilizes the ability of RCA to detect very small amounts of DNA coupled with microsphere-immobilization resulting in an assay which is at least 50 times more sensitive than RIA. Further, this assay method requires very low volume of sample (5 μL), and can be easily adapted to detect other autoantibodies at similar sensitivities while reducing the assay time to ~6 hours. This powerful technique could enable detection of T1DM markers much earlier than current methods and enable earlier intervention to deter the progression of disease. In addition, the modularity of this assay would have implications for enhancing the sensitivities of any standard ELISA technique.

COMPLEMENT-FIXING ISLET-CELL ANTIBODIES IN TYPE I DIABETES AND IN SUSCEPTIBLE PATIENTS WITH AUTOIMMUNE DISEASES

The Lancet ◽  
1980 ◽  
Vol 315 (8183) ◽  
pp. 1418-1419 ◽  
Author(s):  
Corrado Betterle ◽  
Antonio Caretto ◽  
Antonio Tiengo ◽  
Alfonso Trevisan
Keyword(s):  
Autoimmune Diseases ◽  
Islet Cell ◽  
Type I Diabetes ◽  
Islet Cell Antibodies ◽  
Type I

scholarly journals NK Cells in Autoimmune Diseases: Protective or Pathogenic?

2021 ◽  
Vol 12 ◽  
Author(s):  
Meifang Liu ◽  
Shujuan Liang ◽  
Cai Zhang
Keyword(s):  
Immune System ◽  
Autoimmune Diseases ◽  
Nk Cells ◽  
Lupus Erythematosus ◽  
Nk Cell ◽  
Current Knowledge ◽  
Type I Diabetes ◽  
Cell Subset ◽  
Type I ◽  
Autoantibody Production

Autoimmune diseases generally result from the loss of self-tolerance (i.e., failure of the immune system to distinguish self from non-self), and are characterized by autoantibody production and hyperactivation of T cells, which leads to damage of specific or multiple organs. Thus, autoimmune diseases can be classified as organ-specific or systemic. Genetic and environmental factors contribute to the development of autoimmunity. Recent studies have demonstrated the contribution of innate immunity to the onset of autoimmune diseases. Natural killer (NK) cells, which are key components of the innate immune system, have been implicated in the development of multiple autoimmune diseases such as systemic lupus erythematosus, type I diabetes mellitus, and autoimmune liver disease. However, NK cells have both protective and pathogenic roles in autoimmunity depending on the NK cell subset, microenvironment, and disease type or stage. In this work, we review the current knowledge of the varied roles of NK cell subsets in systemic and organic-specific autoimmune diseases and their clinical potential as therapeutic targets.

Effect of jerusalem artichoke extract on the functioning of malate dehydrogenase in the liver of rats with alloxan diabetes

2021 ◽  
Vol 67 (2) ◽  
pp. 144-149
Author(s):  
A.T. Eprintsev ◽  
N.V. Selivanova ◽  
A.V. Moiseenko
Keyword(s):  
Malate Dehydrogenase ◽  
Alloxan Diabetes ◽  
Blood Glucose Concentration ◽  
Type I Diabetes ◽  
Jerusalem Artichoke ◽  
Point Of View ◽  
The Body ◽  
Type I ◽  
Experimental Type ◽  
Encoding Genes

An increase in the activity and the appearance of a new isoform of NAD-dependent malate dehydrogenase (MDH; EC 1.1.1.37) has been detected in the liver of rats with alloxan diabetes was revealed. This confirms the possibility of MDH involvement in the adaptive reaction of the body under oxidative tress caused by biochemical changes in diabetic animals. The increase in the hepatic MDH activity in rats with experimental type I diabetes mellitus (T1DM) is associated with the formation of an additional MDH isoform in peroxisomes. Data on the expression of the MDH encoding genes mdh1 and mdh2 confirm that in T1DM the increase in MDH activity occurs at the level of transcription of MDH encoding genes. The use of the extract of Helianthus tuberosus led to a marked decrease in the blood glucose concentration of rats with alloxan diabetes, abolished by the change in transcriptional activity of the studied genes and blocked the formation of new MDH isoforms in rats with experimental alloxan diabetes. This suggest that extract of H. tuberosus may be of considerable interest from the point of view of pharmacological correction of metabolic changes during the development of pathologies of this kind.

Pathogenesis

2020 ◽  
pp. 48-87
Keyword(s):  
Autoimmune Diseases ◽  
Type I Diabetes ◽  
Complex Interaction ◽  
Specific Gene ◽  
Graves Disease ◽  
Type I ◽  
Vdr Gene ◽  
Organ Specific ◽  
Ifn Γ ◽  
Thyroid Antigen

Hashimoto's thyroiditis (HT) is one of the most prevalent autoimmune diseases provoked in genetically susceptible individuals by several triggers. Immune-regulatory genes such as HLA, CTLA-4, and PTPN22 play a major role in the pathogenesis of autoimmune thyroiditis. The thyroid-specific gene currently showing the association with HT (and also Graves' disease) is the gene for thyroglobulin (Tg). The VDR gene is another HT predisposing gene, common for other organ-specific autoimmune diseases such as type-I diabetes or Addison's disease. Furthermore, cytokine genes such as IFN-γ, IL-4, or TGF-β indicate the association with the development and severity of HT. A complex interaction between genetic and non-genetic factors results in enhanced thyroid antigen presentation and reduced immune tolerance leading to predominantly Th1-type autoimmunity, thyroid destruction, and clinical disease. The exact mechanisms of initiation and progression of HT are yet to be clarified. This chapter explores the pathogenesis of Hashimoto's disease.

Autoantibodies to insulin do appear in non-diabetic patients with autoimmune disorders: Comparison with anti-immunoglobulin antibodies and other autoimmune phenomena

1990 ◽  
Vol 122 (2) ◽  
pp. 303-308 ◽  
Author(s):  
Umberto Di Mario ◽  
Riccardo Perfetti ◽  
Emanuela Anastasi ◽  
Giovanna Contreas ◽  
Laura Crisà ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Type I Diabetes ◽  
Primary Hypothyroidism ◽  
Insulin Autoantibodies ◽  
Diabetic Patients ◽  
Graves Disease ◽  
Type I ◽  
Serum Samples

Abstract Insulin- and anti-immunoglobulin-antibodies have been recently reported in pre-diabetic subjects: the former has been proposed as a predictive marker of Type I diabetes in non-diabetic-subjects. To evaluate the diabetes-related specificity of these antibodies, the presence of insulin autoantibodies, using a recently developed and highly sensitive competitive radioimmune assay, and of anti-immunoglobulin antibodies together with that of immune complexes and of other autoantibodies has been investigated in patients with organ- or non-organ-specific autoimmune diseases. One hundred and eleven serum samples were assayed from patients with Graves' disease, primary hypothyroidism, chronic autoimmune thyroiditis, Addison's disease, chronic autoimmune hepatitis, pernicious anemia, lupus erythematosus, and rheumatoid arthritis, together with 45 serum samples from normal subjects. From patients with autoimmune diseases, 32.4% of all sera revealed values of insulin autoantibodies above the limit of positivity (p<0.001); anti-immunoglobulin antibodies were present in 4.1% of patients (NS); immune complexes were found in 19.5% (NS) of all patients, but in 38% of patients with Graves' disease and chronic hepatitis (p<0.02). There was a trend for multiple autoantibody positivity to be associated with high levels of insulin autoantibodies (p<0.05). Thus, whereas contrary to expectation anti-immunoglobulin antibodies are not associated with non-diabetes-related autoimmune diseases, increased humoral immunoresponsiveness to endogenous insulin appears to be related to autoimmunity in general rather than restricted to Type I diabetes.

scholarly journals Apert syndrom: a literature review and own clinical case

2020 ◽  
pp. 55-58
Author(s):  
V.M. Husiev ◽  
◽  
D.S. Khapchenkova ◽  
V.E. Kleban ◽  
◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Clinical Case ◽  
Clinical Symptoms ◽  
Proximal Phalanx ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Apert Syndrome ◽  
Type I ◽  
Hands And Feet ◽  
Type V

Acrocephalosyndactyly (ACS) is a group of multiple malformations, the main clinical manifestations of which are acrocephaly and syndactyly. The most common forms are Apert (type I), Pfeiffer (type V), Setra–Hotzen (type II) syndromes. Apert syndrome is the most explored and common form of all types of ACS and Apert syndrome is estimated to occur in 1 in: 100 000 newborns. The syndrome is inherited in an autosomal dominant manner. If the gene is carried by one of the parents, the risk of having a child with Apert syndrome is 50%. The syndrome genome (FGFR2) is located on the long arm of chromosome 10 at locus 10q26. Apert syndrome occurs due to mutations at this locus, but the children karyotype is not changed. The pathognomonic clinical signs of Apert syndrome are craniofacial dysostosis and symmetrical syndactyly of the hands and feet. Acrocephaly («tower skull») — is a consequence of early synostosis of some sutures of the skull. Orbital hypertelorism and exophthalmos are referred to typical facial changes. Among other abnormalities there are heart and vascular defects (25%), cleft palate, malformations of the gastrointestinal tract and kidneys. The diagnosis is made on the basis of clinical symptoms. No treatment has been developed. Life expectancy is short. Purpose — to present a clinical case of a newborn with Apert syndrome. Clinical case. Apert syndrome was suspected prenatally, confirmed after birth. The newborn girl had the characteristic signs of the above-described pathology: «tower head», hypertelorism, saddle bridge of the nose, closed large fontanelle, phalanges of the first finger were wide, the proximal phalanx was triangular, complete cutaneous syndactyly of the II–IV fingers was observed symmetrical on both upper extremities; on the lower extremities — thickening of the proximal phalanges of the big toes, complete cutaneous syndactyly of the II–IV toes. Conclusions. The article describes a clinical case of a child with Apert syndrome. Prenatal diagnosis takes one of the leading places in confirming genetic abnormalities, determining the prognosis for life. Genetic counseling for parents is necessary and important at all stages of pregnancy planning. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: Apert syndrome, children, prenatal diagnosis.

HAEMOSTASEOLOGICAL CHANGES IN DIABETIC CHILDREN (HUMAN INSULIN VERSUS PORCINE INSULIN

1987 ◽  
Author(s):  
U Nowak-Göttl ◽  
W D Kreuz ◽  
M John ◽  
B Krackhardt ◽  
H-P Grüttner ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Human Insulin ◽  
Type I Diabetes ◽  
Clinical Signs ◽  
Porcine Insulin ◽  
Control Group ◽  
Type I ◽  
Irreversible Damage ◽  
Diabetic Children ◽  
Spontaneous Platelet Aggregation

Changes of haemostaseological parameters are involved in pathogenesis of diabetic angiopathy. However it is not yet clear whether they are cause or consequence of the endothelial damage. We investigated coagulation parameters in 84 children with type I diabetes mellitus without clinical signs of vascular disease.Compared to the control group no significant changes could be seen in fibrinogen, plasminogen, protein C, α 1 antichymotrypsin, β-thrombo-globulin and ristocetin - induced aggregation.Additionally we could observe significant differences in patients treated with human insulin to those treated with porcine insulin. Spontaneous platelet aggregation (PAT III) and factor VIII C correlated to the duration of diabetes. Also to the mean metabolic equilibrium (HBA1) correlations could be found. Spontaneous platelet aggregation seems to be a useful parameter to assess the onset of atherosclerotic diseases in diabetic children. High values of von Willebrand factor may indicate reversible and/or irreversible damage of vascular endothelium.

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