Islet cell and XXXX autoantibodies in subjects at high risk for development of type 1 ( @entity2690 -dependent) diabetes mellitus: the Lyon family study.

@entity1 @entity6 @entity4106 @entity2690 @entity209 @entity413 @entity4107
Genetic determination as well as prospective analysis of islet cell autoantibodies and autoantibodies to @entity2690 were conducted in a population of 479 first degree relatives of 174 Type 1 ( @entity2690 -dependent) @entity6 @entity1 . Analysis of HLA haplotypes within families illustrated the high frequency of @entity4106 and @entity4107 alleles with preferential transmission from parent to both affected and unaffected offspring. @entity4107 was preferentially associated with DQw3.2 (TA10-) in 60/73 (82.2%) @entity1 and 101/127 (79.5%) relatives. Relatives have been followed for a period of 800 subject-years. Twenty-two out of 430 relatives (5.1%) were found islet cell antibodies (ICA-IgG) positive. Seven sera with low titres became negative 6 months later at two different determinations. Fifteen sera ICA-IgG and ICA-protein A positive with high titres remained positive thereafter. Half of the ICA positive relatives were also found @entity2690 autoantibodies (IAA) positive. All but 3 ICA negative relatives did not have IAA in their sera. Analysis of IAA specificity with competition experiments indicated that most antibodies recognised epitopes shared between @entity1 and pork insulins while four were specific for @entity1 @entity2690 determinants. Analysis of class I and class II HLA antigen distribution indicated no particular allelic restriction in antibody positive individuals. Metabolic status of antibody positive relatives was determined with oral and intravenous charge of @entity413 . Two haplo-identical @entity4106 -DQw2 brothers became @entity6 during the study. One @entity1 and one mother both with @entity4107 -DQw3.2 became intolerant to @entity413 . Each of these relatives had high titre ICA prior to @entity209 .(ABSTRACT TRUNCATED AT 250 WORDS)
