The Journal of clinical endocrinology and metabolism · 2025
Insulitis and Exocrinitis in Autoantibody-positive Nondiabetic Individuals: Role of HLA Genotypes.
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Diedisheim Marc, Mallone Roberto, Pugliese Alberto, Dubois-Laforgue Danièle, Larger Etienne
Аннотация
CONTEXT: Type 1 diabetes (T1D) is characterized by the presence of autoantibodies on a genetic background largely determined by HLA class II haplotypes. Stage 1 T1D is characterized by the presence of multiple autoantibodies and normoglycemia.
OBJECTIVE: To investigate the prevalence of high-risk HLA-DQB1 haplotypes and the extent of islet autoimmunity in pancreatic tissues from nondiabetic organ donors with autoantibodies.
DESIGN: We analyzed 117 virtual pancreatic slides from 30 antibody-positive nondiabetic donors from the Network for Pancreatic Organ Donors with Diabetes (nPOD).
PATIENTS: Thirty nondiabetic individuals positive for ≥1 autoantibody. HLA haplotypes were classified as at risk (DQ2, namely DQB1*02:01 and/or DQ8, namely DQB1*03:02), protective (DQ6, namely DQB1*06:02) or neutral (other HLA-DQ alleles).
MAIN OUTCOME MEASURE: CD3+ lymphocyte infiltration of both endocrine and exocrine pancreas, according to HLA.
RESULTS: Among these 30 individuals with a median age of 25 years (interquartile range 21-39); median body mass index 24 kg/m2 (21-30), 23 were single autoantibody-positive and 7 were positive for 2 autoantibodies. β-cell mass was normal in all. HLA-DQ allele distribution was similar to that of autoantibody-negative nondiabetic nPOD donors and differed from that of nPOD donors with stage 3 T1D. Insulitis was identified only in 1 case. CD3+ lymphocyte densities did no correlate with HLA status or autoantibody number or titers, neither in islets nor in the exocrine pancreas.
CONCLUSION: Contrary to stage 3 T1D, autoantibody-positive donors had normal β-cell mass and no significant insulitis, suggesting heterogeneity in the progression of autoimmunity, even in the presence of genetic risk, rather than a uniform slow-progressing process.
OBJECTIVE: To investigate the prevalence of high-risk HLA-DQB1 haplotypes and the extent of islet autoimmunity in pancreatic tissues from nondiabetic organ donors with autoantibodies.
DESIGN: We analyzed 117 virtual pancreatic slides from 30 antibody-positive nondiabetic donors from the Network for Pancreatic Organ Donors with Diabetes (nPOD).
PATIENTS: Thirty nondiabetic individuals positive for ≥1 autoantibody. HLA haplotypes were classified as at risk (DQ2, namely DQB1*02:01 and/or DQ8, namely DQB1*03:02), protective (DQ6, namely DQB1*06:02) or neutral (other HLA-DQ alleles).
MAIN OUTCOME MEASURE: CD3+ lymphocyte infiltration of both endocrine and exocrine pancreas, according to HLA.
RESULTS: Among these 30 individuals with a median age of 25 years (interquartile range 21-39); median body mass index 24 kg/m2 (21-30), 23 were single autoantibody-positive and 7 were positive for 2 autoantibodies. β-cell mass was normal in all. HLA-DQ allele distribution was similar to that of autoantibody-negative nondiabetic nPOD donors and differed from that of nPOD donors with stage 3 T1D. Insulitis was identified only in 1 case. CD3+ lymphocyte densities did no correlate with HLA status or autoantibody number or titers, neither in islets nor in the exocrine pancreas.
CONCLUSION: Contrary to stage 3 T1D, autoantibody-positive donors had normal β-cell mass and no significant insulitis, suggesting heterogeneity in the progression of autoimmunity, even in the presence of genetic risk, rather than a uniform slow-progressing process.