Dec 19, 2008
Researchers Funded in Part by Society’s Promise:2010 Campaign Use Novel Technology to Identify Antibody Patterns in Blood Samples from People with MS
A team funded by the National MS Society used novel technology to screen the immune response in blood samples from people with various courses of MS, and were able to differentiate between different types of MS and MS patterns of damage, based on distinct immune antibody signatures against different immune targets. Francisco Quintana, PhD, Howard Weiner, MD (Harvard Medical School, Boston) and colleagues reported findings that involved a collaboration with Claudia Lucchinetti, MD (Mayo Clinic, Rochester, MN). Dr. Lucchinetti is lead investigator of the Society’s MS Lesion Project, funded through the Promise: 2010 campaign. The results could ultimately lead to laboratory tests that help diagnose MS and predict its course. (Proceedings of the National Academy of Sciences U S A. 2008 Dec 2;105(48):18889-94)
Background: MS is a highly unpredictable disease that is often difficult to diagnose because there is no specific, single clinical or laboratory test that can tell whether a person has the disease. Not only are the symptoms or even timing of attacks unpredictable, there are also no laboratory or clinical tests that can predict the future course of the disease. The study of other autoimmune diseases has shown that autoantibodies, a family of proteins produced by the immune system, can be used to monitor disease.
Novel technologies such as “antigen microarrays” could help to discover molecules that may be used as “markers” to predict MS disease activity and progression. Antigen microarrays are glass slides dotted with thousands of molecules that are often attacked in autoimmune diseases. When a blood sample from a person without autoimmune disease is put on the array, the person’s antibodies largely ignore the molecules. In people with autoimmune disease, however, antibodies from the blood will latch on to their target molecules; a fluorescent probe is then added to detect and count the attacking antibodies.
The Study: Dr. Weiner and colleagues developed an antigen microarray using 362 molecules relating to nerve fiber-insulating myelin (a major target in MS), inflammation, or antigens associated with other neurological diseases. In one study, they identified a pattern of antibody reactivity that distinguished 38 people with relapsing-remitting MS from 30 controls without MS with a significant degree of accuracy. Among these 94 antibody reactivities, 90 demonstrated increased activity and 4 had decreased activity in MS versus controls. To determine if such patterns were specific for MS, the team investigated blood samples as well from people with systemic lupus erythematosus (an autoimmune disease), and adrenoleukodystrophy and Alzheimer’s disease (diseases with neuroinflammatory components). They found that antibody patterns detected on antigen microarrays discriminated MS from these other diseases.
Dr. Weiner’s group also used microarrays to compare the immune response in 37 people with primary-progressive MS and 37 controls without MS. Again, they identified unique antibody patterns. Unlike relapsing-remitting MS, in primary progressive MS, most of the antibodies were decreased in activity compared to non-disease controls rather than increased. Also, heat shock proteins (small, possibly protective proteins released by cells) were reacted to by people with RR MS, but not those with PP MS. Comparing 37 people with RR MS and 30 people with secondary-progressive MS, the team found different antibody signatures, and again, greater responses to heat shock proteins in RR MS.
Collaboration with The MS Lesion Project
Finally, the group compared findings to samples obtained from Dr. Lucchinetti and the MS Lesion Project. Project investigators have amassed a large collection of tissue samples from people with MS and have found four distinct types of lesions (patches of disease activity and damage) that differ in the pattern of myelin damage and immune response.
Examining samples from 62 people and comparing the results with antigen microarrays, Dr. Weiner’s team found that unique antibody patterns were associated with different lesion patterns. Previous research suggested that people with one of these patterns respond to plasma exchange therapy – a treatment used occasionally to treat individuals experiencing severe MS attacks that do not respond to standard steroid therapy. This suggests that in the future, a non-invasive blood test may be able to distinguish an individual’s underlying pathology and help with treatment decisions.
Comment: “These findings show why we live in a truly exciting time for MS research,” said John Richert, MD, Executive Vice President Of Research & Clinical Programs at the National MS Society. “The use of microarrays by Dr. Weiner’s team, and their collaboration with MS Lesion Project investigators, show how advances in technology are moving us toward the day when a blood test could help doctors diagnose and track MS, and immediately identify patients who will respond to specific treatments.”