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OBJECTIVE—Autoimmune thyroid disease (AIT), celiac disease, and Addison’s disease are characterized by the presence of autoantibodies: thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in AIT, tissue transglutaminase antibody (TTGAb) in celiac disease, and 21-hydroxylase antibody (21-OHAb) in Addison’s disease. The objective of this study was to define the prevalence of these autoantibodies and clinical disease in a population with type 1 diabetes. RESEARCH DESIGN AND METHODS—We screened 814 individuals with type 1 diabetes for TPOAb, TGAb, TTGAb, and 21-OHAb. Clinical disease was defined by chart review. Factors related to the presence of autoimmunity and clinical disease including age at onset of type 1 diabetes, duration of diabetes, age at screening, sex, and the presence of autoantibodies were reviewed. RESULTS—The most common autoantibodies expressed were TPOAb and/or TGAb (29%), followed by TTGAb (10.1%) and 21-OHAb (1.6%). Specific HLA DR/DQ genotypes were associated with the highest risk for expression of 21-OHAb (DRB1*0404-DQ8, DR3-DQ2) and TTGAb (DR3-DQ2- DR3-DQ2). The expression of thyroid autoantibodies was related to 21-OHAb but not to TTGAb. The presence of autoantibodies was associated with and predictive of disease. CONCLUSIONS—In this large cohort of individuals with type 1 diabetes, the expression of organ-specific autoantibodies was very high. The grouping of autoantibody expression suggests common factors contributing to the clustering.

How plants adapt to low temperature is not well understood. To identify components involved in low-temperature signaling, we characterized the previously isolated chilling-sensitive2 mutant (chs2) of Arabidopsis (Arabidopsis thaliana). This mutant grew normally at 22°C but showed phenotypes similar to activation of defense responses when shifted to temperatures below 16°C. These phenotypes include yellowish and collapsed leaves, increased electrolyte leakage, up-regulation of PATHOGENESIS RELATED genes, and accumulation of excess hydrogen peroxide and salicylic acid (SA). Moreover, the chs2 mutant was seedling lethal when germinated at or shifted for more than 3 d to low temperatures of 4°C to 12°C. Map-based cloning revealed that a single amino acid substitution occurred in the TIR-NB-LRR (for Toll/Interleukin-1 receptor-nucleotide-binding Leucine-rich repeat)-type resistance (R) protein RPP4 (for Recognition of Peronospora parasitica4), which causes a deregulation of the R protein in a temperature-dependent manner. The chs2 mutation led to an increase in the mutated RPP4 mRNA transcript, activation of defense responses, and an induction of cell death at low temperatures. In addition, a chs2 intragenic suppressor, in which the mutation occurs in the conserved NB domain, abolished defense responses at lower temperatures. Genetic analyses of chs2 in combination with known SA pathway and immune signaling mutants indicate that the chs2-conferred temperature sensitivity requires ENHANCED DISEASE SUSCEPTIBILITY1, REQUIRED FOR Mla12 RESISTANCE, and SUPPRESSOR OF G2 ALLELE OF skp1 but does not require PHYTOALEXIN DEFICIENT4, NONEXPRESSOR OF PR GENES1, or SA. This study reveals that an activated TIR-NB-LRR protein has a large impact on temperature sensitivity in plant growth and survival.

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