Presence of the human leukocyte antigen class II gene DRB1*1101 Predicts interferon γ levels and disease recurrence in melanoma patients

Background: Increased interferon γ (IFN-γ) levels are an independent predictor of melanoma recurrence. Human leukocyte antigen (HLA) class II genes can regulate cytokine production; we investigated whether these genes would predict IFN-γ levels and recurrence in melanoma patients. Methods: Of 591 patients who presented with localized melanoma, 579 underwent identification of HLA class II alleles; 233 melanoma patients and 90 controls underwent determination of plasma IFN-γ levels. HLA class II genes were examined for association with IFN-γ levels and disease recurrence. Results: After a median follow-up of 60 months, melanoma patients with IFN-γ levels above the mean control value were more likely to have developed disease recurrence compared with patients with levels below the mean. The HLA class II gene HLA-DRB1*1101 was the strongest predictor of recurrence, and HLA-DRB1*1101-positive melanoma patients had increased levels of IFN-γ compared with patients lacking the gene. Conclusions: Among patients with localized melanoma, both HLA-DRB1*1101 and increased IFN-γ levels were associated with an increased risk for recurrence; HLA-DRB1*1101-positive patients had relatively increased levels of IFN-γ. HLA class II genes may mediate cytokine production in melanoma patients, and this mechanism may help determine the risk of disease recurrence.