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Study Identifies Possible Target of Immune Attacks in Some People with MS

Summary
An international team of researchers have identified a protein that may be a target of the immune attack in some people with MS. An immune response to this protein – a protein called "KIR4.1," which is found on several types of brain cells – was observed in the serum of 47% of people with MS who were tested. Further research is needed to confirm these findings, and to understand what the role of this protein may play in MS and its potential for developing new treatments. [Rajneesh Srivastava, M.Sc., Muhammad Aslam, Ph.D., Sudhakar Reddy Kalluri, M.Sc., Lucas Schirmer, M.D., Dorothea Buck, M.D., Björn Tackenberg, M.D., Veit Rothhammer, M.D., Andrew Chan, M.D., Ralf Gold, M.D., Achim Berthele, M.D., Jeffrey L. Bennett, M.D., Thomas Korn, M.D., and Bernhard Hemmer, M.D. N Engl J Med 2012; 367:115-123 July 12, 2012]

Details
The spinal fluid of most people with MS contains increased amounts of a type of antibody called IgG, which are present almost exclusively in infectious and inflammatory disorders and are usually directed against the disease-causing agent. Previous attempts to identify antigens to which antibodies are targeted in MS have failed. The current study focused on the serum portion of blood samples from people with MS and from others, rather than on spinal fluid.

In a series of experiments, the research team screened serum samples from people with MS and observed that IgG antibodies were attaching themselves to specific myelin-making cells. They identified the protein KIR4.1 as the target of the IgG reaction. KIR4.1 is an ion channel; these are proteins that are active on the surfaces of several types of brain cells and are critical for cell function. The team then developed a method of testing people for the presence of antibodies against KIR4.1 in serum samples, and found antibodies to KIR4.1 in a substantial proportion of people with MS in comparison with others tested. The antibodies were found in serum of 186 of 397 (46.9%) people with MS, versus only 3 out of 329 people with other neurologic disorders, and in none out of 59 people without disease.

Further studies revealed that when anti-KIR4.1 antibodies that were obtained from people with MS were injected into mice, abnormalities in the nervous system occurred. In previous studies, KIR4.1 has been shown to be important in myelin formation, leading the team to conclude that KIR4.1 is a plausible candidate to be a target of the immune attack in at least some people who have MS. The investigators did not observe any clinical or other differences in people with MS who had the antibodies versus those who did not. How this protein may be involved in MS, and whether this finding will lead to new approaches to treating MS, awaits further research.

Source: National MS Society (USA) www.nmss.org

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