The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes.
OBJECTIVE
Evidence that the beta cells of human patients with type 1 diabetes can be infected with enterovirus is accumulating, but it remains unclear whether such infections occur at high frequency and are important in the disease process. We have now assessed the prevalence of enteroviral capsid protein vp1 (vp1) staining in a large cohort of autopsy pancreases of recent-onset type 1 diabetic patients and a range of controls.


METHODS
Serial sections of paraffin-embedded pancreatic autopsy samples from 72 recent-onset type 1 diabetes patients and up to 161 controls were immunostained for insulin, glucagon, vp1, double-stranded RNA activated protein kinase R (PKR) and MHC class I.


RESULTS
vp1-immunopositive cells were detected in multiple islets of 44 out of 72 young recent-onset type 1 diabetic patients, compared with a total of only three islets in three out of 50 neonatal and paediatric normal controls. vp1 staining was restricted to insulin-containing beta cells. Among the control pancreases, vp1 immunopositivity was also observed in some islets from ten out of 25 type 2 diabetic patients. A strong correlation was established between islet cell vp1 positivity and PKR production in insulin-containing islets of both type 1 and type 2 diabetic patients, consistent with a persistent viral infection of the islets.


CONCLUSIONS
Immunoreactive vp1 is commonly found in the islets of recent-onset type 1 diabetes patients, but only rarely in normal paediatric controls. vp1 immunostaining was also observed in some islets of type 2 diabetes patients, suggesting that the phenomenon is not restricted to type 1 diabetes patients.
Richardson
S J
SJ
Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Plymouth, UK.
Willcox
A
A
Bone
A J
AJ
Foulis
A K
AK
Morgan
N G
NG
D000293:Adolescent; D000328:Adult; D036022:Capsid Proteins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000821:virology*; D004770:Enterovirus / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007515:Islets of Langerhans / Q000378:metabolism* / Q000821:virology*; D008297:Male; D055815:Young Adult
D036022:Capsid Proteins