Table 1.
Recent evidence on role of virus in islet cell autoimmunity and T1D.
| Author & year (reference) | Type of study (case/control) | Test and Sample | Virus | Findings |
|---|---|---|---|---|
|
Schulte BM et al. 2010 [21] |
Case control (10/20) | RT PCR/plama, PBMC, throat, stool | Enterovirus (EV) | All controls are negative. 4/10 PBMC samples, only 1/10 stool samples positive for EV PCR. None of the throat samples are positive, which argues against acute infection, but probably delayed clearance of EV |
|
Laitinen OH et al. 2013 [22] |
Nested case control Study samples from the DIPP cohort (183/366) |
Antibodies | Coxsackie B1 (CB1) | CB1 is associated with increased risk of beta cell autoimmunity, strongest when infection occurred few months before Islet AA appeared (OR: 1.5, 95% CI: 1.0–2.2) CB3, CB6 appear to reduce risk of autoimmunity |
|
Oikarinen S et al. 2013 [23] |
Case control (249/249) | Antibodies | Coxsackie B1 (CB1) | CB1 antibodies are more frequently seen in those with T1D (OR: 1.7, 95% CI: 1.0–2.9) |
|
Stene LC et al. 2010 [24] |
Prospective study in 140 cases seroconverted for IAA from DAISY cohort | RT PCR Blood, rectal swab |
EV | Risk of progression from islet cell autoimmunity to clinical T1D is significantly higher following detection of EV RNA. |
|
Salminen KK et al. 2004 [25] |
Case control From DIPP cohort (12/53) |
Antibodies, RT PCR stool & serum | EV | 83% cases had at least one EV infection before developing Islet AA, while only 42% controls had EV by the same age (p = 0.006) |
|
Dahlquist GG et al. 2004 [26] |
Case control (542/542) | RT PCR of postnatal Day2–4 blood spot samples | EV | Early (fetal, neonatal) EV infection may play a role in T1D pathogenesis (OR: 1.98, 95% CI; 1.04–3.77). No difference seen with CMV, Parvo-B19 |
| Sadeharju K et al. 2003 [27] | Case control (19/84) From TRIGR cohort |
Antibodies and RT PCR | EV | AA-positive children had more enterovirus infections than AA-negative children before the appearance of AA (0·83 versus 0·29 infection per child, P = 0·01) |
| Hiemstra HS et al. 2001 [28] | Clonal CD4+ T cells reactive to GAD65 - from a prediabetic stiff-man syndrome patient. | Synthetic peptide libraries that bind to HLA-DR3, are screened | Cytomegalovirus (CMV) | GAR-65 specific T-cells cross-react with a peptide of hCMV major DNA binding protein, resulting in possible loss of T cell tolerance to GAD65. |
| Honeyman MC et al. 2010 [29] | Comparative | Rotavirus (RV) | Peptides in VP7, immunogenic protein of RV have significant similarity to T cell epitope peptides in IA2 and GAD65. Molecular mimicry with RV could promote autoimmunity to islet antigens. |
|
| Bian X et al. 2016 [30] | Case control Case/control; 42/42 |
Antibodies | Epstein-Barr virus (EBV) | Positive EBV antibody response is associated with significantly higher cases of T1D (OR: 6.6, 95% CI: 2.0–25.7) |
| Nilsson AL et al. 2015 [31] | Case control Case: control: 69/294 |
Antibodies | Parechovirus (PV) | Ljungan virus antibodies correlated with insulin AA, especially in young HLA-DQ8 subjects, suggesting a possible role in T1D. |
| Tapia G et al. 2011 [32] | Nested case control Case/control: 27/53 The MIDIA study cohort |
PCR Fecal samples |
Parechovirus (PV) | Weak association, if PV infection in 3 months prior to development of autoimmunity, warranting further investigation |
DIPP: Diabetes Prediction and Prevention; DAISY: Diabetes and Autoimmunity Study in the Young; TRIGR: Trial to Reduce IDDM in Genetically at Risk; MIDIA: Norwegian acronym for “Environmental Triggers of Type 1 Diabetes” study; AA: Autoantibodies; GAD65: Glutamic acid decarboxylase 65; IA2: Tyrosine phosphatase-like insulinoma Ag 2; PBMC: Peripheral blood mononuclear cells.