Small study begins to uncover the role of antibodies to KIR4.1 in MS

Antibodies to the potassium channel KIR4.1 have been discovered in a cohort of people who later developed multiple sclerosis, and not in healthy controls, suggesting that anti-KIR4.1 antibodies may play a role in disease pathogenesis.

In an abstract released Feb. 21 in advance of the annual meeting of the American Academy of Neurology, Dr. Viola Biberacher of Technical University Munich and her colleagues, examined blood samples that had been collected from 16 MS patients between 2 and 9 months before their first clinical attack. The investigators also looked at earlier samples from the same cohort taken up to 6 years before the first attack.

In the cohort, seven patients were positive for anti-KIR4.1 antibodies, two showed borderline activity, and seven were negative. Anti-KIR4.1 antibodies were found in samples taken several years before the first clinical attack, and antibody titers varied at different time points before the first attack; titers before and after disease onset did not differ significantly. None of the 16 age- and sex-matched healthy controls had antibodies to KIR4.1.

Dr. Bernhard Hemmer, also of Technical University Munich and the corresponding author of the study, had been part of the research team that first established KIR4.1 as an immune target in MS. In an observational study of patients with active MS (n = 397), compared with patients with other neurological diseases (n = 329) and healthy blood donors (n = 59), anti-KIR4.1 antibodies were found in almost half (47%) of blood samples from people with MS. No evidence of anti-KIR4 antibodies were found in the healthy controls, and they occurred in less than 1% of people with other neurological diseases (N. Engl. J. Med. 2012;367:115-23).

In the current study as well, about half of the patients who went on to develop MS had antibodies to KIR4.1. The full results of the study will be presented at the meeting in Philadelphia.

In an interview, Dr. Hemmer said that because of the very small sample size of patients in this study, these results must be interpreted with caution. "Replication in independent cohorts is essential," he said.

Dr. Hemmer added that while anti-KIR4.1 antibodies appear to be present in about half of MS patients, "we have not observed a particular phenotype of MS to be associated with these antibodies. However, larger studies are underway to address this issue."

If KIR4.1 is proves to be a relevant immune target in MS, something that will take additional studies to confirm, treatment might involve specific immune therapies that could focus on silencing antibodies to KIR4.1, Dr. Hemmer said. "I could also envision drugs that protect the KIR4.1 channel from damage, or enhance its function if the antibody is disturbed or dysregulated in the MS lesion. But all these therapies require first additional studies to strengthen the hypothesis that the channel plays an important role in MS."

Further studies are looking at expression of KIR4.1 in the brain and MS lesions, and investigating cellular immune responses to KIR4.1.

Currently, no commercial assay is available for KIR4.1, as the protein is difficult to express and purify. "We are working on this too, but it will take time," Dr. Hemmer said.

The KIR4.1 study was funded by the German Ministry for Education and Research and the German Competence Network for Multiple Sclerosis. Dr. Biberacher reported having no conflicts of interest related to the study, but several coauthors hold a patent on KIR4.1 antibody testing in MS. Dr. Hemmer has received past support from Roche, Biogen Idec, Bayer, Novartis, Merck Serono, Metanomics, and Teva.

Antibodies to the potassium channel KIR4.1 have been discovered in a cohort of people who later developed multiple sclerosis, and not in healthy controls, suggesting that anti-KIR4.1 antibodies may play a role in disease pathogenesis.

In an abstract released Feb. 21 in advance of the annual meeting of the American Academy of Neurology, Dr. Viola Biberacher of Technical University Munich and her colleagues, examined blood samples that had been collected from 16 MS patients between 2 and 9 months before their first clinical attack. The investigators also looked at earlier samples from the same cohort taken up to 6 years before the first attack.

In the cohort, seven patients were positive for anti-KIR4.1 antibodies, two showed borderline activity, and seven were negative. Anti-KIR4.1 antibodies were found in samples taken several years before the first clinical attack, and antibody titers varied at different time points before the first attack; titers before and after disease onset did not differ significantly. None of the 16 age- and sex-matched healthy controls had antibodies to KIR4.1.

Dr. Bernhard Hemmer, also of Technical University Munich and the corresponding author of the study, had been part of the research team that first established KIR4.1 as an immune target in MS. In an observational study of patients with active MS (n = 397), compared with patients with other neurological diseases (n = 329) and healthy blood donors (n = 59), anti-KIR4.1 antibodies were found in almost half (47%) of blood samples from people with MS. No evidence of anti-KIR4 antibodies were found in the healthy controls, and they occurred in less than 1% of people with other neurological diseases (N. Engl. J. Med. 2012;367:115-23).

In the current study as well, about half of the patients who went on to develop MS had antibodies to KIR4.1. The full results of the study will be presented at the meeting in Philadelphia.

In an interview, Dr. Hemmer said that because of the very small sample size of patients in this study, these results must be interpreted with caution. "Replication in independent cohorts is essential," he said.

Dr. Hemmer added that while anti-KIR4.1 antibodies appear to be present in about half of MS patients, "we have not observed a particular phenotype of MS to be associated with these antibodies. However, larger studies are underway to address this issue."

If KIR4.1 is proves to be a relevant immune target in MS, something that will take additional studies to confirm, treatment might involve specific immune therapies that could focus on silencing antibodies to KIR4.1, Dr. Hemmer said. "I could also envision drugs that protect the KIR4.1 channel from damage, or enhance its function if the antibody is disturbed or dysregulated in the MS lesion. But all these therapies require first additional studies to strengthen the hypothesis that the channel plays an important role in MS."

Further studies are looking at expression of KIR4.1 in the brain and MS lesions, and investigating cellular immune responses to KIR4.1.

Currently, no commercial assay is available for KIR4.1, as the protein is difficult to express and purify. "We are working on this too, but it will take time," Dr. Hemmer said.

The KIR4.1 study was funded by the German Ministry for Education and Research and the German Competence Network for Multiple Sclerosis. Dr. Biberacher reported having no conflicts of interest related to the study, but several coauthors hold a patent on KIR4.1 antibody testing in MS. Dr. Hemmer has received past support from Roche, Biogen Idec, Bayer, Novartis, Merck Serono, Metanomics, and Teva.

Antibodies to the potassium channel KIR4.1 have been discovered in a cohort of people who later developed multiple sclerosis, and not in healthy controls, suggesting that anti-KIR4.1 antibodies may play a role in disease pathogenesis.

In an abstract released Feb. 21 in advance of the annual meeting of the American Academy of Neurology, Dr. Viola Biberacher of Technical University Munich and her colleagues, examined blood samples that had been collected from 16 MS patients between 2 and 9 months before their first clinical attack. The investigators also looked at earlier samples from the same cohort taken up to 6 years before the first attack.

In the cohort, seven patients were positive for anti-KIR4.1 antibodies, two showed borderline activity, and seven were negative. Anti-KIR4.1 antibodies were found in samples taken several years before the first clinical attack, and antibody titers varied at different time points before the first attack; titers before and after disease onset did not differ significantly. None of the 16 age- and sex-matched healthy controls had antibodies to KIR4.1.

Dr. Bernhard Hemmer, also of Technical University Munich and the corresponding author of the study, had been part of the research team that first established KIR4.1 as an immune target in MS. In an observational study of patients with active MS (n = 397), compared with patients with other neurological diseases (n = 329) and healthy blood donors (n = 59), anti-KIR4.1 antibodies were found in almost half (47%) of blood samples from people with MS. No evidence of anti-KIR4 antibodies were found in the healthy controls, and they occurred in less than 1% of people with other neurological diseases (N. Engl. J. Med. 2012;367:115-23).

In the current study as well, about half of the patients who went on to develop MS had antibodies to KIR4.1. The full results of the study will be presented at the meeting in Philadelphia.

In an interview, Dr. Hemmer said that because of the very small sample size of patients in this study, these results must be interpreted with caution. "Replication in independent cohorts is essential," he said.

Dr. Hemmer added that while anti-KIR4.1 antibodies appear to be present in about half of MS patients, "we have not observed a particular phenotype of MS to be associated with these antibodies. However, larger studies are underway to address this issue."

If KIR4.1 is proves to be a relevant immune target in MS, something that will take additional studies to confirm, treatment might involve specific immune therapies that could focus on silencing antibodies to KIR4.1, Dr. Hemmer said. "I could also envision drugs that protect the KIR4.1 channel from damage, or enhance its function if the antibody is disturbed or dysregulated in the MS lesion. But all these therapies require first additional studies to strengthen the hypothesis that the channel plays an important role in MS."

Further studies are looking at expression of KIR4.1 in the brain and MS lesions, and investigating cellular immune responses to KIR4.1.

Currently, no commercial assay is available for KIR4.1, as the protein is difficult to express and purify. "We are working on this too, but it will take time," Dr. Hemmer said.

The KIR4.1 study was funded by the German Ministry for Education and Research and the German Competence Network for Multiple Sclerosis. Dr. Biberacher reported having no conflicts of interest related to the study, but several coauthors hold a patent on KIR4.1 antibody testing in MS. Dr. Hemmer has received past support from Roche, Biogen Idec, Bayer, Novartis, Merck Serono, Metanomics, and Teva.