Human Monocytes - CD14, CD16 - Ziegler-Heitbrock

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Islet-specific T-cell responses and proinflammatory monocytes define subtypes of autoantibody-negative ketosis-prone diabetes.

Abstract

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.

Authors: Brooks-Worrell BM1, Iyer D, Coraza I, Hampe CS, Nalini R, Ozer K, Narla R, Palmer JP, Balasubramanyam A.
Journal: Diabetes Care. ;36:4098-103
Year: 2013
PubMed: Find in PubMed