Myelin Basic Protein-Specific TCR/HLA-DRB5*01:01 Transgenic Mice Support the Etiologic Role of DRB5*01:01 in Multiple Sclerosis
- Jacqueline A. Quandt*,1,
- Jaebong Huh*,
- Mirza Baig*,
- Karen Yao*,
- Naoko Ito†,
- Mark Bryant‡,
- Kazuyuki Kawamura*,
- Clemencia Pinilla§,
- Henry F. McFarland*,
- Roland Martin*,2,3 and
- Kouichi Ito*,†,3
- *Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892;
- †Department of Neurology, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854;
- ‡Division of Veterinary Resources, Office of Research Services, National Institutes of Health, Bethesda, MD 20892; and
- §Torrey Pines Institute for Molecular Studies, San Diego, CA 92121
- ↵1 Current address: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
- ↵2 Current address: Department of Neuroimmunology and Multiple Sclerosis Research, Neurology Clinic, University Hospital Zürich, University of Zürich, Zürich, Switzerland.
- Address correspondence and reprint requests to Prof. Jacqueline A. Quandt or Prof. Kouichi Ito, Department of Pathology and Laboratory Medicine, University of British Columbia, G227-2211 Wesbrook Mall, Vancouver, British Columbia V6T 2B5, Canada (J.A.Q.) or Department of Neurology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, SPH/RWJMS Building, Room 184, 683 Hoes Lane, Piscataway, NJ 08854 (K.I.). E-mail addresses: firstname.lastname@example.org(J.A.Q.) or email@example.com (K.I.)
- ↵3 R.M. and K.I. contributed equally to this work.
Genetic susceptibility to multiple sclerosis (MS) has been linked to the HLA-DR15 haplotype consisting of DRB1*15:01(DR2b) and DRB5*01:01(DR2a) alleles. Given almost complete linkage disequilibrium of the two alleles, recent studies suggested differential roles in susceptibility (DR2b) or protection from MS (DR2a). Our objective was to assess the potential contribution of DR2a to disease etiology in MS using a humanized model of autoimmunity. To assess the potential contribution of DR2a to disease etiology, we created DR2a humanized transgenic (Tg) mice and subsequently crossed them to Tg mice expressing TL3A6, an MS patient-derived myelin basic protein 83-99–specific TCR. In TL3A6/DR2a Tg mice, CD4 Tg T cells escape thymic and peripheral deletion and initiate spontaneous experimental autoimmune encephalomyelitis (EAE) at low rates, depending on the level of DR2a expression. The ability to induce active EAE was also increased in animals expressing higher levels of DR2a. Inflammatory infiltrates and neuronal damage were present throughout the spinal cord, consistent with a classical ascending EAE phenotype with minor involvement of the cerebellum, brainstem, and peripheral nerve roots in spontaneous, as well as actively induced, disease. These studies emphasize the pathologic contribution of the DR2a allele to the development of autoimmunity when expressed as the sole MHC class II molecule, as well as strongly argue for DR2a as a contributor to the CNS autoimmunity in MS.
- This work was supported by the National Institutes of Health intramural program and in part by National Institutes of Health Grant R21 AI067474 (to K.I.), with additional support from the Multiple Sclerosis National Research Institute. J.A.Q. was supported by fellowships from the Multiple Sclerosis Society of Canada and the National Multiple Sclerosis Society.
- The online version of this article contains supplemental material.
- Received January 9, 2012.
- Accepted July 16, 2012.
Dr. Baig was just featured in reviewit Magazine, below is the featured story!
Creating comprehensive personalized treatment regimes for pain.
Over the course of our lives, almost 80% of Americans will be affected by back-related pain. The common misconception that there is no good solution to chronic back and neck pain leads many of us to avoid seeking treatment entirely. For neurosurgeon, Dr. Mirza Baig, there is nothing more important than quality of life, and with his new neurosurgery practice in North Houston he is working to provide chronic pain sufferers with the options – patient education, non-surgical and surgical alternatives and proven outcomes they deserve. “It’s important to diagnose the reason for the pain and build a personalized plan to focus on recovery.” says Dr. Baig.
People who are living with chronic back pain often feel like they have little or no options; they live with their pain, wait to seek treatment, or make a decision to avoid treatment based on the experience of a friend of family member.With this in mind, Dr. Baig conducts a comprehensive diagnosis—including detailed discussion on any previous treatments—and carefully educates patients, providing the information required to make informed decisions.Understanding their condition and the options available to them offers Dr. Baig’s patients a greater sense of empowerment, allowing them take an active role in their own recovery.
With a doctorate degree in medicine (M.D.), a doctorate in Molecular Genetics (Ph.D.) from Howard University with graduate research at National Institute of Health in Bethesda Maryland. Along with his Neurological Surgery training from Ohio State University in Columbus, Ohio, Dr. Baig has devoted a large part of his academic career to research. After his mother succumbed to the neurological disorder Guillain-Barre syndrome during his second year of medical school, Dr. Baig made the decision to study neuroimmunology, focusing his area of research on multiple sclerosis (M.S.). Since that time, Dr. Baig has authored 26 peer-reviewed articles and book chapters and presented at over 17 national and international conferences of neurosurgical societies and associations.
It’s this strong academic background and desire to continue pushing the limitations of modern medicine that puts Dr. Baig at the forefront of neurosurgical treatment. “In every occupation you get comfortable with a procedure or a way of doing something so you stick with it,” Dr. Baig explains. “If it works for you, there’s no reason to try something new. In medicine that just doesn’t apply. You have to implement evidence-based medicine and incorporate latest non-surgical and surgical remedies for the person.” Dr. Baig continues to pursue further medical innovations with projects such as robotic spine surgery he has designed to automate aspects of spinal surgery.
While advancements in the field of spinal surgery have improved patient outcomes, as a conservative neurosurgeon Dr. Baig believes there are also a large number of medical alternatives to surgery that can provide patients with simple and effective solutions. Many common spine-related problems ranging from neck and back pain can be treated with simpler solutions such as physical therapy, pain management and chiropractic care. Working in conjunction with this wide array of specialists, Dr. Baig is able to provide patients with positive outcomes using carefully planned, comprehensive managed care. With only one out of every 12 patients ultimately requiring surgical intervention, Dr. Baig’s customized treatment plans ensure the best outcome while getting individual patients back to full function as quickly and effectively as possible.
In addition to his focus on non-invasive treatment for chronic neck and back pain, as a neurosurgeon Dr. Baig and performs spinal surgery for conditions including lumber disc herniation, spinal stenosis and spondylosis, and treats patients with brain tumors, aneurysms and headaches.
Dr. Baig believes that it is possible for his patients to achieve a superior quality of life, one where pain is not a daily companion. He stresses the need for patient education/empowerment and believes that people who are struggling with pain do have options—options that can lead them to a better, pain-free life.
Sitting in an office chair for prolonged periods of time can definitely cause low back pain or worsen an existing back or neck problem. The main reason behind this is that sitting, in an office chair or in general, is a static posture that increases stress in the back, neck, shoulders, arms and legs, and in particular, can add large amounts of pressure to the back muscles and spinal discs.
When sitting in an office chair for a long period, the natural tendency for most people is to slouch over or slouch down in the chair, and this posture can overstretch the spinal ligaments and strain the discs and surrounding structures in the spine. Over time, incorrect sitting posture can damage spinal structures and contribute to or worsen back and neck pain.