Lymphopenia in H5N1 patients in Northern Viet Nam: kinetics and subsets
Session IV – Fox, Annette
Annette Fox1, Heiman Wertheim1, Walter Taylor1, Cameron Simmons1, Nguyen Hong Ha2, Nguyen Quoc Thai2, Nguyen Vu Trung2, Tao Dong3, Nguyen Duc Hien2, Nguyen Van Kinh2, Jeremy Farrar1, Peter Horby1
1. Oxford University Clinical Research Unit,Vietnam
2. National Institute for Infectious and Tropical Diseases
3. Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University.
Abstract:
H5N1 patient mortality is high despite antivirals. Further understanding of H5N1 pathology is required to develop new treatments. To date, lymphocyte count findings have been reported for 112 H5N1 patients: 18 from Hong Kong (1997); 12 from Thailand (2004); 20 from Vietnam (2004-2005); 7 from Turkey (2005-2006); 29 from Indonesia (2005-2006) and 26 from China (2005-2006). Lymphopenia is frequently observed and tends to be more pronounced in those with severe and fatal disease. This was not observed for the series from China where most patients had severe disease and different H5N1 virus clades were involved. Little is known of the kinetics, subsets involved or mechanisms of lymphopenia and thus whether lymphopenia contributes directly to disease severity. We have conducted a retrospective review of clinical records for 48 patients admitted to hospitals in Ha Noi, Viet Nam in 2004 and 2005, and have prospectively assessed 9 H5N1 patients admitted in 2007 and 2008. The patients include those infected with clade 1 and clade 2.3.4 H5N1.
While many patients were lymphopenic on admission, nadir total, CD4 and CD8 lymphocyte counts occurred 10-20 days after onset. Lymphopenia involved both CD4 and CD8 T cells and CD4:CD8 ratios were inverted in H5N1 but not seasonal flu patients. CD4 counts and CD4:CD8 ratios were significantly lower in patients with fatal disease and in survivors that were hospitalized for more than 40 days. Prospective data revealed that the percentage of CD4 and CD8 T cells expressing CD69 was high and greater in patients with fatal disease whereas CXCR3 expression was reduced. These findings are suggestive of aberrant T cell activation. In mouse models of sepsis lymphopenia caused by apoptosis contributes directly to mortality and children with severe seasonal flu exhibit inadequate, rather than excessive immune responses, and apoptosis. It will be important to determine whether lymphocytes are also apoptosing and/or functionally impaired in H5N1 patients.
