Table 1.
Characteristic features of the eligible proteomic studies
| References | Study group | Control group | Sample type | Discovery method | Validation method | Number of Proteins Identified by Disease Progression | ||
|---|---|---|---|---|---|---|---|---|
| Clinical definition (Disease condition and sample size) |
Demographics (Age and sex, location/ ethnicity) |
Clinical definition (Disease condition and sample size) |
Demographics (Age and sex, location/ethnicity) |
|||||
| Pre-seroconversion | ||||||||
| Moulder et al. 2015, Diabetes | HLA + , autoantibody + . n = 19 | Age (3 m to 12y), Finland (DIPP) | HLA + ., autoantibody-, controls, n = 19 | Age, sex, sample periodicity, and risk group matched | Serum | 2DLC-MS/MS (Untargeted proteomics) | NA |
Pre-seroconversion: 3 (1, 2) Post-seroconversion Longitudinal: 55 (31, 24) Post-seroconversion: 10 (5, 5) |
| Frohnert et al. 2020, Diabetes | Family history of T1D, HLA + , autoantibody + . n = 20, T1D n = 22, |
age (AbPos-0.7–26.5y, T1D- 0.7-15y), and sex (AbPos-8F/12 M & T1D-10F/12 M), Ethnicity (AbPos-15NHW/5RND, T1D-21NHW/1RND), US (DAISY cohort) |
HLA + ., autoantibody- controls n = 25 |
Matched to HLA genotype, age (0.7-23y), sex (13F/12 M), Ethinicity (20NHW/5RND), US. (DAISY cohort) | Serum | LC-SRM-MS, (Targeted proteomics) | NA |
Pre-seroconversion: 3 (2, 1) Post-seroconversion: 2 (1, 1) |
| Webb-Robertson et al. 2023, medRxiv |
HLA + Pre-seroconversion. n = 47, Post-seroconversion. n = 131, Pre T1D n = 70, |
Age (Post-seroconversion ~ 1-23y, pre-T1D ~ 0-29y), Sex: (Pre-seroconversion-19F/28 M, Post-serconversion.- 63F/68 M & pre-T1D –31F/39 M), US (DAISY cohort) |
HLA + controls n = 40 |
Matched to HLA genotype, age (~ 0-14y), and sex (16F/24 M), US. (DAISY cohort) | Plasma | LC-SRM-MS, (Targeted proteomics) | Multiplex assay and ELISA |
Pre-seroconversion: 6 (0, 6) Post-seroconversion, Post IA: 12 (0, 12) |
| Nakayasu et al. 2023, Cell. Rep. Med |
Untargeted: IA endpoint n = 46, T1D endpoint n = 46 Targeted: IA endpoint n = 401, T1D endpoint n = 94 |
Discovery: T1D: 25F/21 M IA: 17F/29 M Validation: T1D: 43F/51 M IA: 179F/222 M (TEDDY cohort) |
Untargeted: IA Control n = 46, T1D Control n = 46 Targeted: IA Control n = 401, T1D Control n = 94 |
Matched to clinical center, gender, family history of T1D age, and HLA-DR-DQ genotypes | Plasma | 2DLC-MS/MS (Untargeted proteomics) | LC-SRM-MS (Targeted proteomics) |
Pre-seroconversion: T1: 4 (3, 1) Post-seroconversion: T2: 72 (44, 28) Pre-seroconversion, Targeted: Month-9: 22 (14, 8) Month-6: 29 (25, 4) Month-3: 25 (13, 11, 1) Post-seroconversion, Targeted: Month 0: 42 (7, 35) Month 3: 21 (6, 14, 1) Month 6: 46 (36, 9, 1) Month 9: 38 (1, 37) Month 12: 21 (10, 11) Month 15: 18 (12, 6) Month 18: 21 (8, 13) |
| Post-seroconversion | ||||||||
| Metz et al. (2008) J Proteome Res | Post-diagnosis n = 10 |
Age (< 30y) (DASP) |
HLA- controls, n = 10 |
Age (< 30y) (DASP) |
Serum & Plasma | 2DLC-MS/MS (Untargeted proteomics) | NA | Post-Diagnosis: 5 (3, 2) |
| Zhi et al. 2011, Mol. Cel. Proteom | Post-diagnosis n = 30 | Age (~ 0 to ~ 90y), US | Autoantibody-. controls, n = 30 | Age and sex Matched, US | Serum | 2-DE gel-MALDI–TOF MS (Untargeted proteomics) | Luminex and ELISA assays | Post-Diagnosis: 17 (11, 6) |
| Chen et al. 2012, J. Proteomics | Post-diagnosis n = 15 | Age and Sex not defined, Taiwan | Controls, n = 5 | Taiwan | Plasma | LC–MS/MS (Untargeted proteomics) | ELISA and Immuno-blotting | Post-Diagnosis: 36 (16, 20) |
| Zhang et al. 2013, J. Exp. Med | Post-diagnosis n = 50 |
Age (10-29y), Sex (15F/35 M), ME (DASP) |
HLA-., controls, n = 100 |
Age (18-28y), Sex (51F/49 M), ME (DASP) |
Serum & Plasma |
LC–MS/MS (Untargeted proteomics) |
LC-SRM-MS (Targeted proteomics) |
Post-Diagnosis: 24 (4, 18, 2) Post Diagnosis Targeted: 24 (8, 11, 5) |
|
Manjunatha et al. 2016, Metabolism |
T1D-PC n = 15 & T1D-GC n = 15 | Age (T1D-PC: 33.6 ± 12.97y, T1D-GC: 34.5 ± 12.48y), US | ND-PC n = 15 & ND-GC n = 15 | Matched for age, sex, and BMI, US | Serum and Plasma | LC–MS/MS (Untargeted proteomics) | NA | Post-Diagnosis: 39 (23, 16) |
| Von Toerne et al. 2017, Diabetologia | T1D family history, Post-seroconversion, rapid T1D n = 15 & slow T1D n = 15 |
Age (Rapid T1D 0.5-33y, slow T1D 9.5–17.5y), Germany (BABYDIAB/BABYDIET birth cohorts) |
T1D family history, autoantibody-. n = 15 |
Age and sex matched, Germany (BABYDIAB/BABYDIET birth cohorts) |
Serum | LC–MS/MS (Untargeted proteomics) | LC-SRM-MS (Targeted proteomics) | Post-seroconversion: 26 (13, 13) |
| do Nascimento de Oliveira et al. 2018, Diabetes Metab Syndr Obes | Post-diagnosis n = 30 | No Familiar history, Age (35.03 ± 8,6), Sex (18F/12F), Brazil | Controls n = 30 | No Familiar history, Age (31.5 ± 10.67), Sex (23F/7 M), and other clinical criteria matched, Brazil | Serum |
LC–MS/MS (Untargeted proteomics) |
NA | Post-Diagnosis: 8 (6, 2) |
| Liu et al. 2018, J. Proteomics |
HLAPos Post-seroconversion, T1D n = 11 |
Age (1-14y), 7 male and 4 female, RND (3) and NHW (8), US (DAISY cohort) |
HLA + , autoantibody- controls n = 10 |
Age 1-14y, 5 male and 5 female, RND (1) and NHW (9), US (DAISY cohort) |
Plasma | LC–MS/MS (Untargeted proteomics) | ELISA | Post-seroconversion: 12 (6, 6) |
| Gourgari et al. 2019, Cadiocasc. Diabetol | Post-Diagnosis, with high risk of cardiovascular disease, n = 26 |
12–21 years old, US |
Controls n = 13 |
Age, sex, BMI, and clinical lipid measurement matched, US |
Plasma |
LC-DIA-MS (Untargeted proteomics) |
NA | Post-Diagnosis: 8 (6, 2) |
A total of 13 studies were identified, and details regarding the various study groups, sampling, and tools for measurement and validation are listed. Italic indicates up-regulated proteins, bold indicates down-regulated proteins and bolditalic indicates conflicting detected peptide abundance. Terms used: HLA human leukocyte antigens, F Female, M Male, NHW non-Hispanic white, RND Race not defined, ME Mixed ethnicity, PC poor glycemic control, GC good glycemic control, ND non-diabetic controls, AbPos Antibody positive, y years, m months, IA Islet autoantibodies, T1D Type 1 diabetes, BMI Body mass index, NA Not applicable, DIPP Diabetes Prediction and Prevention, DAISY Diabetes Auto Immunity Study in the Young, TEDDY: The Environmental Determinants of Diabetes in the Young, DASP: Diabetes Antibody Standardization Program, ELISA enzyme-linked immunosorbent assay, LC–DIA–MS Liquid chromatography data independent-acquisition-mass spectrometry, LC–MS/MS Liquid chromatography–tandem mass spectrometry, LC–SRM–MS Liquid chromatography-selected reaction monitoring-mass spectrometry, and 2-DE gel-MALDI–TOF MS 2D gel electrophoresis matrix-assisted laser desorption/ionization time-of-flight mass spectrometry