Islet-Specific T-Cell Responses and Proinflammatory Monocytes Define Subtypes of Autoantibody-Negative Ketosis-Prone Diabetes
| Autor: | Jerry P. Palmer, Ashok Balasubramanyam, Radhika R. Narla, Christiane S. Hampe, Kerem Ozer, Ramaswami Nalini, Dinakar Iyer, Barbara Brooks-Worrell, Ivonne Coraza |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Endocrinology Diabetes and Metabolism T-Lymphocytes medicine.disease_cause Monocytes Autoimmunity 0302 clinical medicine Insulin-Secreting Cells Child Original Research 0303 health sciences geography.geographical_feature_category Middle Aged Islet Phenotype Female Adult medicine.medical_specialty Diabetic ketoacidosis Adolescent Genotype Immunoblotting 030209 endocrinology & metabolism Real-Time Polymerase Chain Reaction Proinflammatory cytokine Diabetic Ketoacidosis 03 medical and health sciences Young Adult Diabetes mellitus Internal medicine Internal Medicine medicine Humans Pathophysiology/Complications 030304 developmental biology Aged Autoantibodies Advanced and Specialized Nursing geography Type 1 diabetes business.industry Autoantibody DNA HLA-DR Antigens medicine.disease Endocrinology Diabetes Mellitus Type 1 Immunology business Ketosis-prone diabetes Biomarkers Follow-Up Studies |
| Zdroj: | Diabetes Care |
| ISSN: | 1935-5548 0149-5992 |
| Popis: | OBJECTIVE Ketosis-prone diabetes (KPD) is characterized by diabetic ketoacidosis (DKA) in patients lacking typical features of type 1 diabetes. A validated classification scheme for KPD includes two autoantibody-negative (“A−”) phenotypic forms: “A−β−” (lean, early onset, lacking β-cell functional reserve) and “A−β+” (obese, late onset, with substantial β-cell functional reserve after the index episode of DKA). Recent longitudinal analysis of a large KPD cohort revealed that the A−β+ phenotype includes two distinct subtypes distinguished by the index DKA episode having a defined precipitant (“provoked,” with progressive β-cell function loss over time) or no precipitant (“unprovoked,” with sustained β-cell functional reserve). These three A− KPD subtypes are characterized by absence of humoral islet autoimmune markers, but a role for cellular islet autoimmunity is unknown. RESEARCH DESIGN AND METHODS Islet-specific T-cell responses and the percentage of proinflammatory (CD14+CD16+) blood monocytes were measured in A−β− (n = 7), provoked A−β+ (n = 15), and unprovoked A−β+ (n = 13) KPD patients. Genotyping was performed for type 1 diabetes–associated HLA class II alleles. RESULTS Provoked A−β+ and A−β− KPD patients manifested stronger islet-specific T-cell responses (P < 0.03) and higher percentages of proinflammatory CD14+CD16+ monocytes (P < 0.01) than unprovoked A−β+ KPD patients. A significant relationship between type 1 diabetes HLA class II protective alleles and negative T-cell responses was observed. CONCLUSIONS Provoked A−β+ KPD and A−β− KPD are associated with a high frequency of cellular islet autoimmunity and proinflammatory monocyte populations. In contrast, unprovoked A−β+ KPD lacks both humoral and cellular islet autoimmunity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|