Tags

Type your tag names separated by a space and hit enter

Autoantibody negative new onset type 1 diabetic patients lacking high risk HLA alleles in a caucasian population: are these type 1b diabetes cases?

Abstract

BACKGROUND

In Caucasians, a small number of Type 1 diabetic patients do not show evidence of humoral islet autoimmunity at disease onset, at least with common screening procedures. In African- and Hispanic-American diabetic children at time of diagnosis, many show no evidence of autoimmunity but have an atypical clinical form of the disease. According to the recent American Diabetes Association classification, this subgroup of autoantibody negative patients is referred to as Type 1b diabetic subjects. In the present study, a homogeneous Caucasian Type 1 diabetic clinic-based cohort has been evaluated at diagnosis using a large panel of diabetes-related antibodies and then characterized for various genetic features in order to identify newly diagnosed Type 1 diabetics who are potentially autoantibody negative, i.e. possibly referrable to as idiopathic Type 1b diabetes.

METHODS

Newly diagnosed Type 1 diabetic patients of Italian origin (n=141, mean age 12.0+/-7.6 years) were tested for anti-islet cell, anti-insulin, anti-65 kDa isoform of glutamic acid decarboxylase and anti-amino acid residues 256-979 of the tyrosine-phosphatase IA-2 molecule autoantibodies (Step 1). Only those patients found to be autoantibody negative were tested for anti-disialo-ganglioside GD3, anti-thyroid peroxidase, anti-thyroglobulin, anti-21-OH hydroxylase, anti-gastric parietal cell and anti-transglutaminase antibodies (Step 2). Sera negative for the presence of these six autoantibodies as well were characterized in terms of HLA DRB1, DQB1 and CTLA-4.

RESULTS

Six out of 141 subjects (3.5%) were autoantibody negative in the first step of the study and five out of six in the second. These five autoantibody negative patients underwent genetic analysis. Three of them had at least one Type 1 diabetes-related high risk HLA haplotype (3/141, 2.1%) while the remaining two cases showed neutral (DR5-DQB1*0301/DR5-DQB1*0301) or strongly protective (DR2-DQB1*0602/DR2-DQB1*0602) HLA genotypes, respectively (2/141, 1. 4%).

CONCLUSIONS

Clinically defined Type 1 diabetic patients with no sign of autoimmunity do exist in a Caucasian population. These patients (2 out of 141) that cannot be classified as Type 1a diabetic patients lack clinical characteristics of Type 1b diabetes and have to be reconsidered for a more appropriate ADA classification. These data suggest the need of further large population-based studies to understand if Type 1b diabetes really occurs in a Caucasian population. The patient with a strongly protective HLA genotype is particularly interesting considering that among Caucasians only a few sporadic cases with Type 1 diabetes and DQB1*0602, have been reported, none of whom was homozygous at DQB1 locus.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Endocrinology, Clinica Medica 2, University 'La Sapienza', Rome, Italy. ctiberti@uniroma1.it

    , , , , , , , , ,

    Source

    MeSH

    Abatacept
    Adolescent
    Adult
    Age of Onset
    Alleles
    Antigens, CD
    Antigens, Differentiation
    Autoantibodies
    C-Peptide
    CTLA-4 Antigen
    Child
    Child, Preschool
    Diabetes Mellitus, Type 1
    European Continental Ancestry Group
    Exons
    Female
    Glutamate Decarboxylase
    HLA-DQ Antigens
    HLA-DQ beta-Chains
    HLA-DR Antigens
    HLA-DRB1 Chains
    Humans
    Immunoconjugates
    Infant
    Islets of Langerhans
    Isoenzymes
    Italy
    Male
    Risk Factors

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    10707033

    Citation

    Tiberti, C, et al. "Autoantibody Negative New Onset Type 1 Diabetic Patients Lacking High Risk HLA Alleles in a Caucasian Population: Are These Type 1b Diabetes Cases?" Diabetes/metabolism Research and Reviews, vol. 16, no. 1, 2000, pp. 8-14.
    Tiberti C, Buzzetti R, Anastasi E, et al. Autoantibody negative new onset type 1 diabetic patients lacking high risk HLA alleles in a caucasian population: are these type 1b diabetes cases? Diabetes Metab Res Rev. 2000;16(1):8-14.
    Tiberti, C., Buzzetti, R., Anastasi, E., Dotta, F., Vasta, M., Petrone, A., ... Di Mario, U. (2000). Autoantibody negative new onset type 1 diabetic patients lacking high risk HLA alleles in a caucasian population: are these type 1b diabetes cases? Diabetes/metabolism Research and Reviews, 16(1), pp. 8-14.
    Tiberti C, et al. Autoantibody Negative New Onset Type 1 Diabetic Patients Lacking High Risk HLA Alleles in a Caucasian Population: Are These Type 1b Diabetes Cases. Diabetes Metab Res Rev. 2000;16(1):8-14. PubMed PMID: 10707033.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Autoantibody negative new onset type 1 diabetic patients lacking high risk HLA alleles in a caucasian population: are these type 1b diabetes cases? AU - Tiberti,C, AU - Buzzetti,R, AU - Anastasi,E, AU - Dotta,F, AU - Vasta,M, AU - Petrone,A, AU - Cervoni,M, AU - Torresi,P, AU - Vecci,E, AU - Multari,G, AU - Di Mario,U, PY - 2000/3/9/pubmed PY - 2000/5/16/medline PY - 2000/3/9/entrez SP - 8 EP - 14 JF - Diabetes/metabolism research and reviews JO - Diabetes Metab. Res. Rev. VL - 16 IS - 1 N2 - BACKGROUND: In Caucasians, a small number of Type 1 diabetic patients do not show evidence of humoral islet autoimmunity at disease onset, at least with common screening procedures. In African- and Hispanic-American diabetic children at time of diagnosis, many show no evidence of autoimmunity but have an atypical clinical form of the disease. According to the recent American Diabetes Association classification, this subgroup of autoantibody negative patients is referred to as Type 1b diabetic subjects. In the present study, a homogeneous Caucasian Type 1 diabetic clinic-based cohort has been evaluated at diagnosis using a large panel of diabetes-related antibodies and then characterized for various genetic features in order to identify newly diagnosed Type 1 diabetics who are potentially autoantibody negative, i.e. possibly referrable to as idiopathic Type 1b diabetes. METHODS: Newly diagnosed Type 1 diabetic patients of Italian origin (n=141, mean age 12.0+/-7.6 years) were tested for anti-islet cell, anti-insulin, anti-65 kDa isoform of glutamic acid decarboxylase and anti-amino acid residues 256-979 of the tyrosine-phosphatase IA-2 molecule autoantibodies (Step 1). Only those patients found to be autoantibody negative were tested for anti-disialo-ganglioside GD3, anti-thyroid peroxidase, anti-thyroglobulin, anti-21-OH hydroxylase, anti-gastric parietal cell and anti-transglutaminase antibodies (Step 2). Sera negative for the presence of these six autoantibodies as well were characterized in terms of HLA DRB1, DQB1 and CTLA-4. RESULTS: Six out of 141 subjects (3.5%) were autoantibody negative in the first step of the study and five out of six in the second. These five autoantibody negative patients underwent genetic analysis. Three of them had at least one Type 1 diabetes-related high risk HLA haplotype (3/141, 2.1%) while the remaining two cases showed neutral (DR5-DQB1*0301/DR5-DQB1*0301) or strongly protective (DR2-DQB1*0602/DR2-DQB1*0602) HLA genotypes, respectively (2/141, 1. 4%). CONCLUSIONS: Clinically defined Type 1 diabetic patients with no sign of autoimmunity do exist in a Caucasian population. These patients (2 out of 141) that cannot be classified as Type 1a diabetic patients lack clinical characteristics of Type 1b diabetes and have to be reconsidered for a more appropriate ADA classification. These data suggest the need of further large population-based studies to understand if Type 1b diabetes really occurs in a Caucasian population. The patient with a strongly protective HLA genotype is particularly interesting considering that among Caucasians only a few sporadic cases with Type 1 diabetes and DQB1*0602, have been reported, none of whom was homozygous at DQB1 locus. SN - 1520-7552 UR - https://www.unboundmedicine.com/medline/citation/10707033/Autoantibody_negative_new_onset_type_1_diabetic_patients_lacking_high_risk_HLA_alleles_in_a_caucasian_population:_are_these_type_1b_diabetes_cases L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1520-7552&date=2000&volume=16&issue=1&spage=8 DB - PRIME DP - Unbound Medicine ER -