Stress Disorders Linked to Increase Risk of Autoimmune Disease

MedicalResearch.com Interview with:

Huan Song Associated Department of Medical Epidemiology and Biostatistics Karolinska Institutet

Huan Song

Huan Song
Associated
Department of Medical Epidemiology and Biostatistics
Karolinska Institutet

MedicalResearch.com: What is the background for this study?

Response: Earlier findings from our group (e.g. Fang et al., NEJM 2012; Arnberg et al., Lancet Psychiatry 2015; Lu et al., JAMA Oncol 2016; Shen et al., BMJ 2016; Zhu et al., Ann Oncol 2017) have identified pathways through which stressful events contribute to deterioration in human health. With strong animal models and human data supporting a role of stress in immune dysregulation, the hypothesis linking mental distress with autoimmune is indeed plausible. However, the evidence is as yet limited to clinical observations and a few larger observational studies on US veterans, most of them on men only, and some of which have cross-sectional designs and various other methodological shortcomings.

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Autoantibodies Generated By Zika Virus May Explain Some Consequences of Infection

MedicalResearch.com Interview with:

Slobodan Paessler, D.V.M., Ph.D. Associate Professor, Department of Pathology; Director, Galveston National Laboratory Preclinical Studies Core;  Director, Animal Biosafety Level 3, Institute for Human Infections and Immunity; Member, Center for Biodefense & Emerging Infectious Diseases University of Texas Medical Branch  Galveston, TX

Dr. Paessler

Slobodan Paessler, D.V.M., Ph.D.
Professor, Department of Pathology;
Director, Galveston National Laboratory Preclinical Studies Core;
Director, Animal Biosafety Level 3, Institute for Human Infections and Immunity;
Member, Center for Biodefense & Emerging Infectious Diseases
University of Texas Medical Branch
Galveston, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika virus infection is associated with various developmental issues for human embryos such as reduced head growth, reduced brain tissue growth, and damage to brain or eyes. We wanted to better understand if some of these birth defects are caused directly by the Zika virus or maybe by the host response to infection.

In our study we demonstrate that the Zika virus infection induces autoimmune response against the C1q protein. This protein is a very important immune protein as well as one of the essential proteins for healthy brain development. Attacking the C1q protein upon exposure with the Zika virus could contribute to the development of autoimmune disorders and birth defects.  Continue reading

Similar Incidence of Autoimmune and Infectious Brain Inflammatory Disease Encephalitis

MedicalResearch.com Interview with:

Eoin Flanagan, M.B., B.Ch. Mayo Clinic Rochester, Minnesota

Dr. Flanagan

Eoin Flanagan, M.B., B.Ch.
Mayo Clinic
Rochester, Minnesota 

MedicalResearch.com: What is the background for this study?

 

Response: Traditionally it has been thought that infections (e.g., viruses)  account for the majority of encephalitis cases. Recent discoveries of neural autoantibody markers of encephalitis (e.g., NMDA receptor autoantibodies) have led to an appreciation that encephalitis cases can be caused by the body’s own immune system attacking the brain, what we term autoimmune encephalitis. Continue reading

Newly Recognized Connection Between Immune System and Sperm Opens Window to Some Male Infertility and Cancer Vaccine Failures

MedicalResearch.com Interview with:
Kenneth S. K. Tung, M.D.
Professor of Pathology and Microbiology
Director of UVA Research Histology Core
Beirne B. Carter Center for Immunology Research
University of Virginia

MedicalResearch.com: What is the background for this study?

Response: The immune system needs to see tissue antigens to avoid responding to them in order to prevent autoimmune disease development. The current dogma, stated in all Immunology and Reproductive Biology textbooks, considers the sperm antigens in the testis to be exempted from this process. They are considered totally hidden behind a tissue barrier, and are invisible to the immune system.

Because sperm antigens are treated as foreign molecules, they should stimulate strong immune response when employed in cancer vaccines against antigens common to sperm and cancers. It is also believed that sperm molecules are protected by local factors that inhibit inflammation, whereas systemic mechanisms such as regulatory T cells would not exist.

The paradigm has restrained ongoing research on systemic tolerance to sperm, and the need to understanding systemic regulation in infertility research

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Follicular T Cells May Play a Role in Development of Type I Diabetes

MedicalResearch.com Interview with:

Tuure Kinnunen, MD, PhD Academy Research Fellow School of Medicine, University of Eastern Finland Kuopio, Finland

Dr. Tuure Kinnunen

Tuure Kinnunen, MD, PhD
Academy Research Fellow
School of Medicine, University of Eastern Finland
Kuopio, Finland

MedicalResearch.com: What is the background for this study?

Response: Type 1 diabetes is an autoimmune disease where the immune system destroys the insulin-producing beta cells in the pancreas. It typically manifests in childhood and early adolescence.

Diabetes-associated autoantibodies are highly predictive of type 1 diabetes risk and they can be typically detected in the blood of patients even years before the onset of the disease.

Follicular helper T cells are a recently described type of immune cells that have a central role in activating B cells, which in turn are responsible for producing antibodies. Since the emergence of autoantibodies is a common feature of type 1 diabetes development, it is plausible that follicular T helper cells have a role in the disease process. This notion is also supported by evidence recently generated in the murine models of type 1 diabetes.

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New Approach May Cure Autoimmune Diseases By Targeting Just Autoantibody Cells

MedicalResearch.com Interview with:

 credit Paul Foster, Penn Medicine for the photo.

from left to right:
Aimee Payne, MD, PhD – co-senior author
Christoph Ellebrecht, MD – first author
Michael Milone, MD, PhD – co-senior author

Aimee S. Payne, M.D., Ph.D.
Albert M. Kligman Associate Professor of Dermatology
University of Pennsylvania
Philadelphia, PA 19104

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Payne: Autoimmunity occurs when the body’s immune system mistakenly attacks itself, instead of foreign viruses and bacteria. The most common way we treat autoimmunity is to suppress the immune system, but that can be dangerous, with risk of serious and even fatal infections. We have developed a method to use the body’s own immune system to specifically kill the disease-causing autoimmune cells, while sparing the “good” immune cells that protect from infection.

If you think about the way we used to treat cancer, we had no way of targeting the cancer cells specifically, so we just targeted all dividing cells, but this approach led to terrible side effects and even death from therapy. Over the last several decades, tremendous advances have been made identifying cell markers and signaling pathways that are specific to cancer cells, which has greatly reduced the toxicity of cancer treatments. Recently, researchers discovered that they could direct the body’s own immune cells to seek out and kill cancer cells, using a so-called “chimeric antigen receptor” or CAR, a breakthrough in medical technology that has cured previously incurable cancers.

We have re-engineered the CAR approach to specifically target the autoantibody-producing cells, by using the disease autoantigen in a “chimeric autoantibody receptor” or CAAR. We are hopeful that this approach might similarly prove to be a breakthrough in autoimmune disease therapy, since the concept can be extended to any autoantibody-mediated disease for which the autoantigen is known.

MedicalResearch.com: What should readers take away from your report?

Dr. Payne:  Ideally, the CAAR targeted therapy approach would be a one-time disease treatment that would cure autoantibody-mediated diseases, without the risks of generalized immune suppression. In contrast, our current therapies use chronic immune suppression for the goal of disease control, which can greatly reduce the quality of life for affected patients.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Payne: We are actively seeking to move this technology forward into human clinical trials. Our immediate focus is to use CAAR technology to cure pemphigus in dogs. Dogs are one of the only animals other than humans that naturally develop pemphigus. If we could safely treat and potentially cure pemphigus in dogs, that would be compelling evidence to encourage doctors and patients to enroll for clinical trials of CAAR therapy.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Rosacea May Be A Marker For Autoimmune Disease

Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital, University of Copenhagen Hellerup, Denmark

Dr. Alexander Egeberg

MedicalResearch.com Interview with:
Alexander Egeberg, MD PhD

National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology
Herlev and Gentofte University Hospital
University of Copenhagen
Hellerup, Denmark

Medical Research: What is the background for this study? What are the main findings?

Dr. Egeberg: A recent genome-wide association study (GWAS) identified 90 shared genetic regions associated with celiac disease, type 1 diabetes mellitus, multiple sclerosis, and rheumatoid arthritis, respectively. Similarly, a newly published GWAS identified shared risk loci between rosacea, type 1 diabetes, and celiac disease. In the present study of 6,759 patients with rosacea and 33,795 control subjects, rosacea was associated with a 2 to 3-fold higher risk of these four conditions, particularly among women.

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Celiac Disease Implies Higher Risk of Other Autoimmune Diseases

MedicalResearch.com Interview with:
Louise Emilsson, MD PhD, Postdoc
Primary Care Research unit
Vårdcentralen Värmlands Nysäter and Institute of Health and Society
University of Oslo

MedicalResearch: What is the background for this study?

Dr. Emilsson: Genetics is considered an important factor in the development of celiac disease and other autoimmune diseases. For e.g. the prevalence of celiac disease is about 10% in first-degree relatives of celiac patients compared to about 1% in the general population. Several earlier genome-wide association study (GWAS) studies have established shared genetic features also in-between different autoimmune diseases, however, very little is known about the risk of developing other autoimmune diseases in relatives of celiac patients. Therefore we assessed the risk of several other non-celiac autoimmune diseases (Crohn’s disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus or ulcerative colitis) in all first degree relatives and spouses of Swedish celiac patients.

MedicalResearch: What are the main findings?

Dr. Emilsson: The main finding is that both first-degree relatives (+28%) and spouses (+20%) are at increased risk of other autoimmune diseases. There are several plausible explanations for these findings. One is of course that individuals with celiac disease and their first-degree relatives share a genetic autoimmune predisposition, another potential explanation involves shared environment (relevant for both first-degree relatives and spouses) but finally we cannot rule out that a certain degree of increased awareness of signs and symptoms in both first-degree relatives and spouses might lead to more examinations and thereby diagnoses (so-called ascertainment bias). Probably all these mechanisms contributed to the finding.

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