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DR human leukocyte antigens and disease severity in chronic hepatitis C
A J Czaja1, H Carpenter, P J Santrach
1Division of Gastroenterology and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Insights
Human leukocyte antigen DR (DR) antigens are not linked to chronic hepatitis C disease severity. However, HLA DR1 is associated with fewer immune manifestations in patients with hepatitis C.
Area of Science:
- Immunogenetics
- Hepatology
- Autoimmunity
Background:
- Immune mechanisms influence chronic hepatitis C (HCV) disease severity.
- Human leukocyte antigen (HLA) DR antigens may play a role in these immune mechanisms.
Purpose of the Study:
- To investigate the association between HLA DR antigens and HCV disease severity at presentation.
- To explore correlations between HLA DR antigens, disease severity, and autoantibodies in HCV patients.
Main Methods:
- Prospective assessment of 64 HCV patients classified by disease severity (mild, moderate, severe).
- Determination of 14 DR antigens using restriction fragment length polymorphism or PCR-sequence specific primers.
- Comparison with 80 healthy subjects for DR antigen frequencies.
Main Results:
- No significant differences in DR antigen frequencies were observed between patients with varying disease severity or compared to normal subjects.
- Patients with autoantibodies or concurrent immunologic diseases showed similar DR antigen frequencies across disease severity groups.
- A lower frequency of HLA DR1 was noted in patients with autoimmune features compared to those without and normal subjects.
Conclusions:
- HLA DR antigens are not associated with disease severity indicators in chronic hepatitis C at presentation.
- Immunologic manifestations do not predict distinct disease severity or genetic predisposition in HCV.
- The presence of HLA DR1 is linked to a reduced frequency of immune manifestations in HCV.
Background/Aims:
Immune mechanisms may modulate disease severity in chronic hepatitis C and the DR human leukocyte antigens may affect these mechanisms. Our aims were to evaluate the association between the DR antigens and disease severity at presentation and to seek correlation between these antigens, disease severity and autoantibodies in this condition.
Methods:
Sixty-four patients were assessed prospectively and classified as having mild, moderate and severe disease by clinical, laboratory and histologic criteria. Fourteen DR antigens were determined by restriction fragment length polymorphism or polymerase chain reaction-sequence specific primers. Eighty normal subjects were typed in a similar fashion.
Results:
Patients with mild (16), moderate (32) and severe (16) disease at presentation were indistinguishable from each other and from normal subjects by the frequencies of each DR antigen. Subsets of patients with different laboratory and histological findings had DR frequencies comparable to those without these findings and to those of normal subjects. Patients with autoantibodies and/or concurrent immunologic diseases had mild (19% versus 32%, p = 0.4), moderate (50% versus 50%) and severe (31% versus 18%, p = 0.4) disease as commonly as other patients. The frequencies of the DR antigens were similar in each category of disease severity. Patients with autoimmune features differed from patients without these features (3% versus 32%, p = 0.002) and normal subjects (3% versus 25%, p = 0.003) by having a lower frequency of HLA DR1.
Conclusions:
The DR antigens are not associated with any index of disease severity at presentation. Immunologic manifestations do not identify patients with a different disease severity or a distinctive genetic predisposition for disease activity. The presence of DR 1 is associated with a lower frequency of immune manifestations.