neuroinflammatory diseases are clinically heterogeneous and one of the major causes of acquired neurological disability . an underlying complex genetic susceptibility may play an important role in their etiologies ; however , the role of genetic factors in determining their clinical features is still unclear . multiple sclerosis ( ms ) , one of the major neuroinflammatory diseases , recently was recognized and subsequently well - characterized in children , but the awareness of pediatricians and pediatric neurologists , especially in asian countries to the occurrence of ms , is still unsatisfactory . some data provided evidences that asian and western type ms are distinct regarding their immunogenetic background ( 1 - 3 ) . acute disseminated encephalomyelitis ( adem ) is a postinfectious encephalitis that is usually preceded by an infectious illness or vaccination . the clinical manifestation has a wide spectrum and complementary examinations are not specific , except for magnetic resonance imaging ( mri ) findings which show multifocal white - matter lesions similar to those seen in ms ( 4 - 9 ) . acute necrotizing encephalopathy ( ane ) , likely postinfectious encephalomyelitis , is not uncommon in asian countries but is very rarely seen in western countries . the etiology is still unknown , but immunogenetic mechanism has been suggested ( 10 - 15 ) . some data suggest that children with postinfectious encephalomyelitis are genetically predisposed to this demyelinating disease ( 16 ) . therefore we studied hla determinants in thirteen children consecutively diagnosed with neuroinflammatory disease to study the immunogenetic peculiarities of neuroinflammatory diseases in korean children . a total of 13 children ( 8 males and 5 females ) with neuroinflammatory diseases were consecutively recruited at the section of pediatric neurology , kyungpook national university hospital , daegu , korea , between january 2000 and april 2003 . the studied subjects included five children with adem , three with ms , three with acute necrotizing encephalopathy , and two with transverse myelitis . three age - matched children with no neurological illnesses were also evaluated as controls . the children with neuroinflammatory diseases and three age - matched children with no neurological illnesses as controls were molecularly typed for hla class ii genes . genomic dna was prepared from peripheral blood leukocytes by using a dna purification kit ( promega , madison , wi , u.s.a . ) according to standard procedures . molecular analysis was performed on hla - drb / hla - dqb genes ( chromosome 6p21 ) of 13 unrelated children with neuroinflammatory diseases using pcr - ssop / ssp kits ( inno - lipa hla - drb , ghent , belgium and pel - freez ssp unitray with taq polymerase , basel , switzerland ) for low and high resolution typing , according to the manufacturer 's instructions along with augmentation of gel immunoelectrophoresis for hla - dqb . as shown in table 2 , the frequency of hla - dr1 * 15 was significantly increased in patients with adem ( 31% ) and the frequency of dqb1 * 06 was also increased in other neuroinflammatory diseases ( 38% ; 4 adem , 1 multiple sclerosis , 1 transverse myelitis ) compared with control subjects as well as known data of hla - drb alleles in koreans . in korean children with multiple sclerosis , the frequencies of hla - drb1 * 1501 , hla - drb5 * 0101 , hla - drb3 * 0301 , and hla - dqb1 * 0602 were not as high as in western children , but the frequencies of hla - drb3 * 0202 ( 100% ) , hla - drb1 * 1302 ( 67% ) , hla - drb3 * 0301 ( 67% ) , and hla - dqb1 * 0301 ( 67% ) were significantly increased instead ( table 3 ) . the frequencies of hla - drb1 * 1501 ( 40% ) and hla - drb5 * 0101 ( 40% ) were significantly increased in children with adem compared with control subjects . in addition , three common alleles , hla - drb1 * 1401 , hla - drb3 * 0202 , and hla - dqb1 * 0502 , were found in children with acute necrotizing encephalopathy with bilateral thalamotegmental involvement ( anebtt ) ( table 4 ) . in the absence of a biological marker , the distinction between adem and ms can not be made with certainty at the time of initial manifestation and a preceding or concurrent viral illness , high lesion load on mri , involvement of the deep gray matter , or absence of oligoclonal bands may be more indicative of adem ( 5 , 17 ) . it will be very interesting if we were able to clarify whether these conditions have their own specific biological markers or share the markers . we sought to assess a possible relationship between hla class ii genes and neuroinflammatory diseases such as ms and adem . this is the pilot study to evaluate the immunogenetic background of neuroinflammatory diseases in asian children . we analyzed hla determinants in thirteen korean children consecutively diagnosed with neuroinflammatory disease . as illustrated in table 1 , adem is still the major condition despite the fact that a lot of children with adem were not enrolled for many reasons . we had two cases of clinically definite multiple sclerosis ( cdms ) who met the diagnostic criteria ( 18 - 20 ) . in addition , there was a child with clinically isolated syndromes ( cis ) suggestive of ms . few pediatric cases of cdms have been reported in korea . however , recently the number is increasing . this is probably due to rapid westernization of the country , availability of clinically qualified experts , and improvement of diagnostic tools . the subjects were genotyped using pcr - ssop / ssp techniques for hla drb / hla dqb genes with augmentation and gel immunoelectrophoresis . as shown in table 2 , the frequencies of hla - dr1 * 15 and dqb1 * 06 were significantly increased in neuroinflammatory diseases compared with control subjects as well as known data of hla - drb alleles in korean ( 21 , 22 ) . the results are similar to previous reports from western countries and partly supports our hypothesis ( 23 ) . the five most common alleles in these children were drb3 * 0202 ( 46% ) , drb1 * 0101 ( 23% ) , drb1 * 1302 ( 23% ) , dqb1 * 0301 ( 23% ) , and dqb1 * 0501 ( 23% ) . like previous japanese studies ( 24 , 25 ) , the frequencies of hla - drb1 * 1501 , hla - drb5 * 0101 , hla - drb3 * 0301 , and hla - dqb1 * 0602 were not as high in korean children with ms as in western children ( 1 - 3 , 26 - 29 ) . a very strong correlation of the condition with hla - drb3 * 0202 , hla - drb1 * 1302 , hla - drb3 * 0301 , and hla - dqb1 * 0301 alleles was verified instead ( table 3 ) . these findings may provide the evidence for correlation of these alleles and susceptibility of korean children to ms . the frequencies of hla - drb1 * 1501 ( 40% ) and hla - drb5 * 0101 ( 40% ) were significantly increased in children with adem compared with control subjects . interestingly , there was one child with a clinically strong feature of adem , but he had the western genotype of ms , hla - drb1 * 1501 and hla - dqb1 * 0602 ( fig . although the same hla determinants were found in this patient as in those with ms , further studies on a larger number of patients with postinfectious encephalomyelitis are needed before we can conclude with certainty that the two diseases share a common genetic propensity . finally , it is noteworthy that three common alleles , hla - drb1 * 1401 , hla - drb3 * 0202 , and hla - dqb1 * 0502 were found in children with anebtt ( table 4 ) . with our limited knowledge , anebtt is not a common illness worldwide and has never been molecularly evaluated , so this result might be valuable . however , further studies are required to elucidate the condition . in conclusion , hla - dr1 * 15 and dqb1 * 06 may be involved in susceptibility to inflammation in korean children . the frequencies of hla - drb1 * 1501 , hla - drb5 * 0101 , hla - drb3 * 0301 , and hla - dqb1 * 0602 were not as high in korean children with ms as in western children . our data may provide further evidence that the immunogenetic background of neuroinflammatory diseases in asians is distinctly different from that in western countries .
the work was done to study immunogenetic peculiarities of neuroinflammatory diseases among korean children . 
 a total of 13 children with neuroinflammatory diseases ( 8 males and 5 females ; mean age 4.62.6 yr ) were consecutively recruited . 
 genomic typing was performed on their hla drb / hla dqb genes using pcr - ssop / ssp techniques with gel immunoelectrophoresis . 
 the frequencies of hla - dr1 * 15 in children with acute disseminated encephalomyelitis ( adem ) ( 31% ) and dqb1 * 06 in other neuroinflammatory diseases ( 38% ) were significantly increased compared with control subjects . the frequencies of hla - drb3 * 0202 ( 100% ) , hla - drb1 * 1302 ( 67% ) , hla - drb3 * 0301 ( 67% ) , and hla - dqb1 * 0301 ( 67% ) were significantly increased in children with multiple sclerosis and the frequencies of hla - drb1 * 1501 ( 40% ) and hla - drb5 * 0101 ( 40% ) were significantly increased in children with adem . 
 hla - drb1 * 1401 , hla - drb3 * 0202 , and hla - dqb1 * 0502 were found in children with acute necrotizing encephalopathy . in conclusion , hla - dr1 * 15 and dqb1 * 06 may be involved in susceptibility to inflammation in korean children . 
 the frequencies of hla - drb1 * 1501 , hla - drb5 * 0101 , hla - drb3 * 0301 , and hla - dqb1 * 0602 were not as high in korean children with multiple sclerosis as in western children . however , hla - drb3 * 0202 was seen in all children with multiple sclerosis . 
 our data may provide further evidence that the immunogenetic background of neuroinflammatory diseases in korean is distinctly different from the ones in western countries . 
 further studies are necessary to confirm this finding .