Breaking News
March 22, 2018 - A retinal implant that is more effective against blindness
March 22, 2018 - New system based on artificial intelligence provides reliable detection of breast cancer
March 22, 2018 - Research offers new understanding about cause of Parkinson’s disease
March 22, 2018 - HORIBA’s Microsemi CRP analyzer improves quality of care in emergency pediatric units, study shows
March 22, 2018 - Range of Vaginal Dryness Products Can Help Postmenopausal Women: Study
March 22, 2018 - Higher Dose Tx Deemed Safe in Pulmonary TB
March 22, 2018 - Discovery of new ALS gene points to cytoskeleton as potential target for drug development
March 22, 2018 - Diet soda associated with higher odds of diabetic retinopathy
March 22, 2018 - LSD reduces ‘sense of self’
March 22, 2018 - Vitamin D deficiency linked to metabolic syndrome in postmenopausal women
March 22, 2018 - Changes in the intestines may be responsible for reversal of diabetes after bariatric surgery
March 22, 2018 - iPads and Cancer; Clot Retrieval and Stroke: It’s PodMed Double T!
March 22, 2018 - Premature births linked to changes in mother’s bacteria
March 22, 2018 - Brain SPECT scans predict treatment outcomes in patients with depression
March 21, 2018 - Researchers succeed in integrating artificial organelles into cells of living organism
March 21, 2018 - Researchers discover ‘missing mutation’ in severe infant epilepsy
March 21, 2018 - Researchers develop statistics-based computational scheme to zoom in on brain function
March 21, 2018 - Verge joins Genomics England’s Discovery Forum industry partnership
March 21, 2018 - Trovagene Announces First Patient Successfully Completes Cycle 1 of Treatment with PCM-075 in Combination with Low Dose Cytarabine (LDAC) in AML Trial
March 21, 2018 - Congenital Cardiac Cath Tx Often Strays from Guidelines
March 21, 2018 - Marked increase in cardiovascular risk factors in women after preeclampsia
March 21, 2018 - New app may help predict, track manic and depressive episodes in bipolar patients
March 21, 2018 - Discovery of genes could lead to development of novel therapies for EBV-related cancers
March 21, 2018 - High-fat, high-cholesterol diet depletes ranks of artery-protecting immune cells
March 21, 2018 - Research misconduct allegations shadow likely CDC appointee
March 21, 2018 - Most Breast Ca Patients Fail to Get Genetic Counseling
March 21, 2018 - Lopsided ear function can lead to lopsided brain development
March 21, 2018 - Acupuncture helps manage menopausal symptoms, review finds
March 21, 2018 - Motor skill training may contribute to reading skills in obese children
March 21, 2018 - Poor dental health may be related to increased diabetes risk
March 21, 2018 - Chronic opioid users at increased risk of complications after spinal fusion surgery
March 21, 2018 - Study uncovers potential therapeutic target against large family of parasites
March 21, 2018 - NSAID use linked to increased risk of atrial fibrillation
March 21, 2018 - Scientists develop brain “stethoscope” that can detect silent seizures
March 21, 2018 - New method predicts effects of global warming on disease
March 21, 2018 - Insurance Company Hurdles Burden Doctors, May Harm Patients
March 21, 2018 - Renal Transplant from HCV-Positive Donors Feasible
March 21, 2018 - Myelodysplastic syndrome: MedlinePlus Medical Encyclopedia
March 21, 2018 - Research reveals brain mechanism involved in language learning
March 21, 2018 - Many parents still hesitate to try early peanut introduction, survey finds
March 21, 2018 - Audiologist urges tinnitus sufferers facing ‘revolving door healthcare’ to seek support
March 21, 2018 - Study reveals impact of prostate cancer on wives and partners of sufferers
March 21, 2018 - ‘Almost a Miracle Drug’: What We Heard This Week
March 21, 2018 - Study shows NIH spent >$100 billion on basic science for new medicines
March 21, 2018 - Columbia researchers identify nerve cells that drive fruit fly’s escape behavior
March 21, 2018 - Sartorius Stedim Biotech selected by ABL Europe to supply single-use process technologies
March 21, 2018 - Increase in coffee consumption may help battle against colon cancer
March 21, 2018 - Hydrogel may accelerate healing of diabetic ulcers
March 21, 2018 - Dermira’s Two Phase 3 Trials Evaluating Olumacostat Glasaretil in Patients with Acne Vulgaris Did Not Meet Co-Primary Endpoints
March 21, 2018 - DePuy Synthes introduces ACTIS Total Hip System for improving initial implant stability
March 21, 2018 - ‘Oh, It Was Nothing’
March 21, 2018 - Herbal drug kratom linked to salmonella illnesses, CDC says
March 21, 2018 - New optical point-of-care device could enhance screening for thyroid nodules
March 21, 2018 - FDA Expands Approval of Adcetris (brentuximab vedotin) for First-Line Treatment of Stage III or IV Classical Hodgkin Lymphoma in Combination with Chemotherapy
March 21, 2018 - Eosinophilic Esophagitis: Late Manifestation of Allergic March
March 21, 2018 - Signaling pathway involving the Golgi apparatus identified in cells with Huntington’s disease
March 21, 2018 - Quintupling inhaled steroid doses may not benefit children with asthma
March 21, 2018 - Study shows clear connection between cardiovascular fitness in middle age and dementia risk
March 21, 2018 - Premature babies have higher risks of health complications in Bangladesh
March 21, 2018 - Child’s temperament and parenting influence weight gain in babies
March 21, 2018 - Researchers find the heart to be capable of arrhythmia termination after local gene therapy
March 21, 2018 - Inhealthcare to provide digital infrastructure for NHS to help protect people from falls
March 21, 2018 - Flu Season Finally Slowing Down
March 21, 2018 - Mixed Results for Shorter DAPT in ACS Patients
March 21, 2018 - Scientists discover fish scale-derived collagen effective for healing wounds
March 21, 2018 - Genomics England announces new partnership to improve efficiency of next-generation sequencing analysis
March 21, 2018 - Adjuvant AC chemotherapy found to be effective in treating HRD-positive breast cancer patients
March 21, 2018 - Researchers identify new treatment targets for lung diseases using big data
March 21, 2018 - Kids see more women in science than five decades ago
March 21, 2018 - Research shows link between chronic fatigue syndrome and lower thyroid hormone levels
March 21, 2018 - Alzheimer’s disease on the rise
March 21, 2018 - Two Agents Equal as Pretreatment for Adrenal Tumor Surgery
March 21, 2018 - ‘Icebreaker’ protein opens genome for T cell development, researchers find
March 21, 2018 - Women in medicine shout #Metoo about sexual harassment at work
March 21, 2018 - Mother’s pre-pregnancy waist size may be linked to child’s autism risk
March 21, 2018 - Second hand marijuana smoke can cause serious damage
March 21, 2018 - International study shows benefits of using MRI at the start of prostate cancer diagnosis
March 20, 2018 - Santhera Reports Outcome of Exploratory Trial with Idebenone in PPMS Conducted at the NIH
March 20, 2018 - ECG Patch Ups At-Home Afib Diagnosis in mSToPS Trial
March 20, 2018 - ROS-scavenging nanozymes for anti-inflammation therapeutics
Team engineers anti-inflammatory antibodies that may treat autoimmune disease

Team engineers anti-inflammatory antibodies that may treat autoimmune disease

image_pdfDownload PDFimage_print

A team of Massachusetts General Hospital (MGH) investigators has found a way to engineer antibodies within an organism, converting autoantibodies that attack “self” tissues into anti-inflammatory antibodies in animal models of two autoimmune diseases. The researchers’ report will be published in the January 25 issue of Cell and has been released online.

“We were able to convert antibodies that cause autoimmune disease into anti-inflammatory antibodies by specifically modifying the sugars attached to the antibodies,” says Robert Anthony, PhD, of the Center for Immunology and Inflammatory Diseases in the MGH Division of Rheumatology, Allergy and Immunology, who led the study. “While more work is required, we hope that this approach of anti-inflammatory antibody conversion will have a beneficial effect on patients suffering from autoimmune and inflammatory diseases.”

Intravenous immunoglobulin (IVIG) – prepared from the antibodies of healthy donors – is used at low doses to treat patients lacking key antibodies. Paradoxically, at high dosage levels IVIG can suppress, rather than enhance the immune response and is used to treat several inflammatory and autoimmune conditions. Whether activated antibodies stimulate an inflammatory or anti-inflammatory response appears to be determined by specific sugar molecules called glycans attached to the Fc region – the tail-like section of a Y-shaped antibody. In previous work, Anthony’s group and others have found that the anti-inflammatory effect of high-dose IVIG can be attributed to a minor fraction of antibodies to which a glycan called sialic acid has been attached to their Fc region.

While glycans are usually attached to the proteins making up antibodies while they are being assembled within cells, recent evidence suggests they could be modified outside of the cellular environment. The MGH team set out to determine whether administration of a transferase, an enzyme that moves chemical groups like glycans from one molecule to another, could convert inflammatory antibodies to anti-inflammatory forms within a living animal.

Since the attachment of sialic acid to an Fc group requires the presence of another glycan called galactose, the team created two enzymes termed B4Fc and ST6Fc, which induce the attachment of galactose and sialic acid respectively. Although intravenous administration of either enzyme alone did not reduce inflammation in a mouse model of rheumatoid arthritis, simultaneous administration of both in a form called B4ST6Fc had anti-inflammatory effects similar to those of high-dose IVIG. B4ST6Fc administration also reduced kidney damage in a mouse model of lupus-related kidney inflammation.

Additional experiments found little evidence that enzyme administration affected antibodies not involved with the specific autoimmune condition and also showed that platelets, which become activated at the site of antibody-driven inflammation, provided the sialic acid and galactose attached to the Fc region by the B4ST6Fc enzyme.

Anthony explains that, while IVIG can be effective against many inflammatory and autoimmune diseases, it is in short supply, the treatment is expensive, and administration is time consuming. “We found that our enzymes were effective at a 400-fold lower dose than high-dose IVIG, and by manipulating the enzymes already in an organism, our method eliminates the need for a lengthy IVIG infusion.” His team will be exploring questions in future studies such as appropriate dosage, optimal administration and whether repeat treatments would be required.

Explore further:
Sugar governs how antibodies work in the immune system

More information:
Cell (2017). DOI: 10.1016/j.cell.2017.11.041

Journal reference:

Provided by:
Massachusetts General Hospital

Tagged with:

About author

Related Articles