Human cytomegalovirus in the pancreas of patients with type 2 diabetes: is there a relation to clinical features, mRNA and protein expression of insulin, somatostatin, and MHC class II?
Human cytomegalovirus (HCMV) was recently demonstrated in the pancreas of about half the patients with type 2 diabetes mellitus in the absence of mumps, rubella or Coxsackie B virus. The present study addresses the question as to whether type 2 diabetes with an HCMV-positive pancreas differs from those with HCMV-negative pancreases with respect to age, sex, treatment, duration of disease, volume densities of B-cells and D-cells, mRNA levels of insulin and somatostatin, islet amyloid peptide deposits and major histocompatibility complex (MHC) class I and class II gene transcription, and protein expression. HCMV-positive type 2 diabetic patients showed a tendency towards a shorter duration of disease and significantly increased levels of MHC class II on RNA. In addition, expression of MHC class II product (HLA-DR) was identified in duct epithelial cells and/or islet cells in 9 diabetic pancreases and in 2 non-diabetic glands. No MHC class I expression could be detected. No other clinical differences between HCMV-positive and HCMV-negative glands were found. All 10 HCMV-positive diabetics showed a strong expression of MHC class II mRNA in the pancreas. By immunocytochemistry, 4 of 10 demonstrated expression on the islets; three of ten also expressed MHC DR beta on ductal cells. This finding might be related to the viral infection, as only 2 of the 9 HCMV-negative patients were HLA-DR beta positive and none of the non-diabetic controls showed increased levels of MHC class II mRNA. These data suggest that HCMV infection in the pancreas is associated with type 2 diabetes. However, no conclusions as to a role of this virus in the aetiopathology of type 2 diabetes can be drawn at present.
Department of Medicine, University of Erlangen-Nünberg, Federal Republic of Germany.
M
M
Löhr
B
B
Bergstrome
R
R
Maekawa
M B
MB
Oldstone
G
G
Klöppel
D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000032:analysis / Q000378:metabolism; D000686:Amyloidosis / Q000150:complications / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics* / Q000302:isolation & purification* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics* / Q000382:microbiology; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007328:Insulin / Q000032:analysis / Q000235:genetics*; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000737:chemistry / Q000382:microbiology* / Q000473:pathology; D010182:Pancreatic Diseases / Q000150:complications / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D013004:Somatostatin / Q000032:analysis / Q000235:genetics*
D000682:Amyloid; D004279:DNA, Viral; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D012333:RNA, Messenger; D013004:Somatostatin