scholarly journals A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen

2021 ◽  
Vol 118 (51) ◽  
pp. e2100687118
Author(s):  
Nils Landegren ◽  
Norito Ishii ◽  
Maribel Aranda-Guillén ◽  
Hörður Ingi Gunnarsson ◽  
Fabian Sardh ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Biomarker Discovery ◽  
Specific Marker ◽  
Clinical Use ◽  
Skin Disorders ◽  
Paraneoplastic Pemphigus ◽  
Human Genes ◽  
Autoimmune Attack ◽  
Transglutaminase 1 ◽  
Critical Challenge

Autoantigen discovery is a critical challenge for the understanding and diagnosis of autoimmune diseases. While autoantibody markers in current clinical use have been identified through studies focused on individual disorders, we postulated that a reverse approach starting with a putative autoantigen to explore multiple disorders might hold promise. We here targeted the epidermal protein transglutaminase 1 (TGM1) as a member of a protein family prone to autoimmune attack. By screening sera from patients with various acquired skin disorders, we identified seropositive subjects with the blistering mucocutaneous disease paraneoplastic pemphigus. Validation in further subjects confirmed TGM1 autoantibodies as a 55% sensitive and 100% specific marker for paraneoplastic pemphigus. This gene-centric approach leverages the wealth of data available for human genes and may prove generally applicable for biomarker discovery in autoimmune diseases.

scholarly journals Making Meaningful Clinical Use of Biomarkers

2017 ◽  
Vol 12 ◽  
pp. 117727191771523 ◽  
Author(s):  
Matthew J Selleck ◽  
Maheswari Senthil ◽  
Nathan R Wall
Keyword(s):  
Biomarker Discovery ◽  
Therapeutic Monitoring ◽  
Clinical Use ◽  
Current State

This review discusses the current state of biomarker discovery for the purposes of diagnostics and therapeutic monitoring. We underscore relevant challenges that have defined the gap between biomarker discovery and meaningful clinical use. We highlight recent advancements in and propose a way to think about future biomarker development.

Antibodies to orbital tissues in thyroid-associated ophthalmopathy

1992 ◽  
Vol 126 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Petros Perros ◽  
Pat Kendall-Taylor
Keyword(s):  
Autoimmune Diseases ◽  
Extraocular Muscle ◽  
Enzyme Linked Immunosorbent Assay ◽  
Eye Muscle ◽  
Autoimmune Attack ◽  
Thyroid Associated Ophthalmopathy ◽  
Binding Antibody ◽  
Antibody Levels ◽  
Orbital Fibroblasts ◽  
Normal Controls

Thyroid-associated ophthalmopathy is thought to be an autoimmune disease affecting the orbit. The precise pathogenetic mechanisms are not known, but extraocular muscle and/or orbital fibroblasts are the likely targets of the autoimmune attack. Sera from 41 normal controls, 79 patients with thyroid-associated ophthalmopathy and 72 patients with other autoimmune diseases were examined for antibodies to cultured orbital fibroblasts and extraocular muscle by enzyme-linked immunosorbent assay. Orbital fibroblast antibody levels varied widely in all subject groups studied, and failed to distinguish patients with thyroid-associated ophthalmopathy from patients with other autoimmune diseases or controls. Eye-muscle binding antibody levels were higher amongst patients with ophthalmopathy compared to normal controls and patients with Graves' hyperthyroidism without clinical evidence of ophthalmopathy. Furthermore, eye-muscle binding antibody levels were found to be particularly high in patients with ophthalmopathy and concurrent dermopathy, and in patients with ophthalmic (euthyroid) Graves' disease.

scholarly journals Bone Markers - Their Nature and Clinical Use

2008 ◽  
Vol 27 (2) ◽  
pp. 117-122
Author(s):  
Manfred Theis
Keyword(s):  
Vitamin D ◽  
Bone Markers ◽  
Cell Types ◽  
Bone Diseases ◽  
Specific Marker ◽  
Clinical Use ◽  
Osteoblastic Activity ◽  
Therapeutic Drugs ◽  
Recent Developments ◽  
Turnover Markers

Bone Markers - Their Nature and Clinical UseBone remodeling units are the centerpiece of bone metabolism. They are fueled by a synchronized and well balanced interaction of osteoclasts and osteoblasts, the activity of which releases specific substances known as bone markers into the blood. Resorption markers result from osteoclastic activity, formation markers from osteoblastic activity, and turnover markers from both cell types. In clinical practice, bone markers are today widely used for monitoring of antiresorptive therapy and patient compliance. There is strong evidence that they are also useful for risk assessment with respect to osteoporosis, here complementing established imaging methods. Other possible and partly not yet investigated indications include monitoring of side-effects of certain therapeutic drugs and oncology. In particular the combination of resorption and formation markers may open up a more differentiated insight into the metabolic situation of a patient's bone. The activity of osteoclasts and osteoblasts is triggered and modulated by numerous factors, some of which are of endocrine nature. Easily measurable in today's laboratory are for instance PTH, calcitonin and vitamin D. While calcitonin is not widely used in osteology, PTH and vitamin D define risk factors for an accelerated loss of bone and impaired mineralization of osteoid with the related diseases of osteoporosis, ricketts and osteomalacia. Recent developments in lab diagnosis of bone diseases focus on rheumatic diseases like rheumatoid arthritis, where anti-CCP is a much more specific marker than the common rheuma factors.

scholarly journals Expression of Immunoregulatory Molecules by Thyrocytes Protects Nonobese Diabetic-H2h4 Mice from Developing Autoimmune Thyroiditis

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1545-1551 ◽  
Author(s):  
Mami Nakahara ◽  
Yuji Nagayama ◽  
Ohki Saitoh ◽  
Rintaro Sogawa ◽  
Shigenobu Tone ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Adenovirus Vector ◽  
Target Tissue ◽  
Tissue Destruction ◽  
Indoleamine 2 ◽  
Nonobese Diabetic ◽  
Autoimmune Attack ◽  
Thyroid Glands ◽  
Organ Specific

One approach to prevent tissue destruction by autoimmune attack in organ-specific autoimmune diseases is to protect the target tissue from autoimmune reaction, regardless of its persistent activity. To provide proof-of-principle for the feasibility of this approach, the immunoregulatory molecules, TNF-related apoptosis-inducing ligand (TRAIL) and indoleamine 2, 3-dioxygenase, were expressed in the thyroid glands using adenovirus vector in nonobese diabetic-H2h4 mice that spontaneously develop thyroiditis. Mice were anesthetized, and the thyroid glands were exposed by neck dissection, followed by in situ infection with adenovirus vector (5 × 1010 particles per mouse) twice or thrice, starting 1 d or 4 wk before mice were supplied with sodium iodine (NaI) water. After 8 wk NaI provision, the extent of thyroiditis, serum titers of antithyroglobulin antibodies, and cytokine expression in the spleen were examined. In situ infection of adenovirus expressing TRAIL or indoleamine 2, 3-dioxygenase, but not green fluorescent protein, significantly suppressed thyroiditis scores. However, antithyroglobulin antibody titers and expression levels of cytokines (interferon-γ and IL-4) in the spleen remained unaltered. Importantly, adenovirus infection 4 wk after NaI provision was also effective at suppressing thyroiditis. The suppressive effect of TRAIL appears to be mediated at least partly by accumulation of CD4+Foxp3+ regulatory T cells into the thyroid glands. Thus, localized expression of immunoregulatory molecules efficiently protected the thyroid glands from autoimmune attack without changing the systemic autoimmunity in nonobese diabetic-H2h4 mice. This kind of immunological intervention, although it does not suppress autoimmune reactivity, may have a potential for treating organ-specific autoimmune diseases. The feasibility of in situ expression of the immuno-regulatory molecules to prevent tissue destruction by autoimmune attack in organ-specific autoimmune diseases is discussed.

Biomarker identification and clinical validation

2016 ◽  
pp. 98-108
Author(s):  
Richard D. Kennedy ◽  
Manuel Salto-Tellez ◽  
D. Paul Harkin ◽  
Patrick G. Johnston
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Biomarker Discovery ◽  
Drug Dosage ◽  
Anatomical Site ◽  
Clinical Validation ◽  
Clinical Use ◽  
Biomarker Identification ◽  
Novel Drugs ◽  
Objectively Measured

Most cancer therapy is given in a ‘one size fits all’ manner depending on the anatomical site involved and basic histopathology, with drug dosage calculated from clinical trials using toxicity as an endpoint. An improved understanding of cancer at a molecular level has led clinicians to question how we develop novel drugs and select appropriate patients in the clinic. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Biomarkers can potentially be used to tailor a patient’s treatment to improve survival and reduce unnecessary toxicity. Though many cancer-related biomarkers have been published in peer-reviewed articles, few have made an impact on patient care because of a failure to demonstrate clinical validity. This chapter explains biomarker discovery and delivery with a view to describing what constitutes a valid biomarker suitable for clinical use.

Biomarker discovery by comprehensive phenotyping for autoimmune diseases

2004 ◽  
Vol 111 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Aaron B Kantor ◽  
Weixun Wang ◽  
Hua Lin ◽  
Harini Govindarajan ◽  
Markus Anderle ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Biomarker Discovery

scholarly journals Applications of Protein Microarrays in Biomarker Discovery for Autoimmune Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Siting Li ◽  
Guang Song ◽  
Yina Bai ◽  
Ning Song ◽  
Jiuliang Zhao ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Biomarker Discovery ◽  
Protein Microarray ◽  
Protein Microarrays ◽  
Microarray Technology ◽  
Serum Samples ◽  
Future Studies ◽  
Key Issues

Dysregulated autoantibodies and cytokines were deemed to provide important cues for potential illnesses, such as various carcinomas and autoimmune diseases. Increasing biotechnological approaches have been applied to screen and identify the specific alterations of these biomolecules as distinctive biomarkers in diseases, especially autoimmune diseases. As a versatile and robust platform, protein microarray technology allows researchers to easily profile dysregulated autoantibodies and cytokines associated with autoimmune diseases using various biological specimens, mainly serum samples. Here, we summarize the applications of protein microarrays in biomarker discovery for autoimmune diseases. In addition, the key issues in the process of using this approach are presented for improving future studies.

scholarly journals The Role of Regulatory B cells in Kidney Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Wang Long ◽  
Hedong Zhang ◽  
Wenjia Yuan ◽  
Gongbin Lan ◽  
Zhi Lin ◽  
...  
Keyword(s):  
B Cells ◽  
Autoimmune Diseases ◽  
Kidney Diseases ◽  
Specific Marker ◽  
Protective Effects ◽  
Regulatory B Cells ◽  
Multiple Phenotypes ◽  
Therapeutic Value ◽  
And Function

B cells, commonly regarded as proinflammatory antibody-producing cells, are detrimental to individuals with autoimmune diseases. However, in recent years, several studies have shown that regulatory B (Breg) cells, an immunosuppressive subset of B cells, may exert protective effects against autoimmune diseases by secretion of inhibitory cytokines such as IL-10. In practice, Breg cells are identified by their production of immune-regulatory cytokines, such as IL-10, TGF-β, and IL-35, however, no specific marker or Breg cell-specific transcription factor has been identified. Multiple phenotypes of Breg cells have been found, whose functions vary according to their phenotype. This review summarizes the discovery, phenotypes, development, and function of Breg cells and highlights their potential therapeutic value in kidney diseases.

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