Cellular Immunological Changes in Patients with LADA Are a Mixture of Those Seen in Patients with Type 1 and Type 2 Diabetes

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2019 Mar 8

PMID 30843600

Citations 16

Authors

K Singh

M Martinell

Z Luo

D Espes

J Stalhammar

S Sandler

P-O Carlsson

Affiliations

Soon will be listed here.

Abstract

There is currently scarce knowledge of the immunological profile of patients with latent autoimmune diabetes mellitus in the adult (LADA) when compared with healthy controls (HC) and patients with classical type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective of this study was to investigate the cellular immunological profile of LADA patients and compare to HC and patients with T1D and T2D. All patients and age-matched HC were recruited from Uppsala County. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine the proportions of immune cells by flow cytometry. Plasma concentrations of the cytokine interleukin (IL)-35 were measured by enzyme-linked immunosorbent assay (ELISA). The proportion of CD11c CD123 antigen-presenting cells (APCs) was lower, while the proportions of CD11c CD123 APCs and IL-35 tolerogenic APCs were higher in LADA patients than in T1D patients. The proportion of CD3 CD56 CD16 natural killer (NK) cells was higher in LADA patients than in both HC and T2D patients. The frequency of IL-35 regulatory T cells and plasma IL-35 concentrations in LADA patients were similar to those in T1D and T2D patients, but lower than in HC. The proportion of regulatory B cells in LADA patients was higher than in healthy controls, T1D and T2D patients, and the frequency of IL-35 regulatory B cells was higher than in T1D patients. LADA presents a mixed cellular immunological pattern with features overlapping with both T1D and T2D.

Citing Articles

Interleukin-35: A key player managing pre-diabetes and chronic inflammatory type 1 autoimmune diabetes.

Chakraborty R, Mukherjee A, Bala A World J Diabetes. 2024; 15(10):2147-2151.

PMID: 39493554 PMC: 11525726. DOI: 10.4239/wjd.v15.i10.2147.

Changes of B cell subsets in different types of diabetes and its effect on the progression of latent autoimmune diabetes in adults.

Wu P, Song Y, Chen Z, Xia J, Zhou Y Endocrine. 2023; 83(3):624-635.

PMID: 37755622 DOI: 10.1007/s12020-023-03539-9.

Variable frequencies of peripheral T-lymphocyte subsets in the diabetes spectrum from type 1 diabetes through latent autoimmune diabetes in adults (LADA) to type 2 diabetes.

Tan T, Xiang Y, Deng C, Cao C, Ren Z, Huang G Front Immunol. 2022; 13:974864.

PMID: 36091068 PMC: 9449581. DOI: 10.3389/fimmu.2022.974864.

Latent autoimmune diabetes in adults in China.

Qiu J, Xiao Z, Zhang Z, Luo S, Zhou Z Front Immunol. 2022; 13:977413.

PMID: 36090989 PMC: 9454334. DOI: 10.3389/fimmu.2022.977413.

Latent autoimmune diabetes in adults: a focus on β-cell protection and therapy.

Yin W, Luo S, Xiao Z, Zhang Z, Liu B, Zhou Z Front Endocrinol (Lausanne). 2022; 13:959011.

PMID: 35992113 PMC: 9389314. DOI: 10.3389/fendo.2022.959011.

References

Levey A, Bosch J, Lewis J, Greene T, Rogers N, Roth D . A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130(6):461-70. DOI: 10.7326/0003-4819-130-6-199903160-00002. View

Cooper M, Fehniger T, Caligiuri M . The biology of human natural killer-cell subsets. Trends Immunol. 2001; 22(11):633-40. DOI: 10.1016/s1471-4906(01)02060-9. View

Bluestone J, Tang Q . How do CD4+CD25+ regulatory T cells control autoimmunity?. Curr Opin Immunol. 2005; 17(6):638-42. DOI: 10.1016/j.coi.2005.09.002. View

Rodacki M, Milech A, de Oliveira J . NK cells and type 1 diabetes. Clin Dev Immunol. 2006; 13(2-4):101-7. PMC: 2270779. DOI: 10.1080/17402520600877182. View

Yang Z, Zhou Z, Tang W, Huang G, Peng J, Li X . [Decrease of FOXP3 mRNA in CD4+ T cells in latent autoimmune diabetes in adult]. Zhonghua Yi Xue Za Zhi. 2007; 86(36):2533-6. View

Mallone R, Martinuzzi E, Blancou P, Novelli G, Afonso G, Dolz M . CD8+ T-cell responses identify beta-cell autoimmunity in human type 1 diabetes. Diabetes. 2007; 56(3):613-21. DOI: 10.2337/db06-1419. View

Niedbala W, Wei X, Cai B, Hueber A, Leung B, McInnes I . IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol. 2007; 37(11):3021-9. DOI: 10.1002/eji.200737810. View

Maruyama T, Watanabe K, Yanagawa T, Kasatani T, Kasuga A, Shimada A . The suppressive effect of anti-asialo GM1 antibody on low-dose streptozotocin-induced diabetes in CD-1 mice. Diabetes Res. 1991; 16(4):171-5. View

Collison L, Workman C, Kuo T, Boyd K, Wang Y, Vignali K . The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature. 2007; 450(7169):566-9. DOI: 10.1038/nature06306. View

10.

Rovati B, Mariucci S, Manzoni M, Bencardino K, Danova M . Flow cytometric detection of circulating dendritic cells in healthy subjects. Eur J Histochem. 2008; 52(1):45-52. DOI: 10.4081/1185. View

11.

Vignali D, Collison L, Workman C . How regulatory T cells work. Nat Rev Immunol. 2008; 8(7):523-32. PMC: 2665249. DOI: 10.1038/nri2343. View

12.

Allen J, Pang K, Skowera A, Ellis R, Rackham C, Lozanoska-Ochser B . Plasmacytoid dendritic cells are proportionally expanded at diagnosis of type 1 diabetes and enhance islet autoantigen presentation to T-cells through immune complex capture. Diabetes. 2008; 58(1):138-45. PMC: 2606862. DOI: 10.2337/db08-0964. View

13.

Poli A, Michel T, Theresine M, Andres E, Hentges F, Zimmer J . CD56bright natural killer (NK) cells: an important NK cell subset. Immunology. 2009; 126(4):458-65. PMC: 2673358. DOI: 10.1111/j.1365-2567.2008.03027.x. View

14.

Zhou X, Bailey-Bucktrout S, Jeker L, Penaranda C, Martinez-Llordella M, Ashby M . Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat Immunol. 2009; 10(9):1000-7. PMC: 2729804. DOI: 10.1038/ni.1774. View

15.

Akesson C, Uvebrant K, Oderup C, Lynch K, Harris R, Lernmark A . Altered natural killer (NK) cell frequency and phenotype in latent autoimmune diabetes in adults (LADA) prior to insulin deficiency. Clin Exp Immunol. 2010; 161(1):48-56. PMC: 2940148. DOI: 10.1111/j.1365-2249.2010.04114.x. View

16.

Sakaguchi S, Miyara M, Costantino C, Hafler D . FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010; 10(7):490-500. DOI: 10.1038/nri2785. View

17.

Collison L, Chaturvedi V, Henderson A, Giacomin P, Guy C, Bankoti J . IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol. 2010; 11(12):1093-101. PMC: 3008395. DOI: 10.1038/ni.1952. View

18.

Calderon B, Carrero J, Miller M, Unanue E . Cellular and molecular events in the localization of diabetogenic T cells to islets of Langerhans. Proc Natl Acad Sci U S A. 2011; 108(4):1561-6. PMC: 3029745. DOI: 10.1073/pnas.1018973108. View

19.

Qin H, Lee I, Panagiotopoulos C, Wang X, Chu A, Utz P . Natural killer cells from children with type 1 diabetes have defects in NKG2D-dependent function and signaling. Diabetes. 2011; 60(3):857-66. PMC: 3046846. DOI: 10.2337/db09-1706. View

20.

Long S, Buckner J . CD4+FOXP3+ T regulatory cells in human autoimmunity: more than a numbers game. J Immunol. 2011; 187(5):2061-6. PMC: 3160735. DOI: 10.4049/jimmunol.1003224. View