HHV6 infection may simply play a role in TA-TMA via GVHD as many studies
identify HHV6 species B as a risk factor for acute GVHD after HSCT
(24). It is also of specific interest that the
cellular receptor for HHV6B in humans is CD46 or Membrane Cofactor
Protein (MCP), a regulator of complement attack on self-cells. In
T-cells, it is documented that HHV6B infection leads to down-regulation
of MCP (25). Although there is no data on MCP
expression on endothelial cells after HHV6B infection, it seems possible
that the same finding could hold true for both cell types, see proposed
mechanism in Figure 1 (26). If MCP expression is
reduced, endothelial cells become more prone to damage via complement
attack. While more data is needed to corroborate this claim, HHV6
induced downregulation of MCP along with promotion of complement
signaling via NETs would serve to further expose endothelial cells to
damage complement attack and therefore promote development of TMA
(27).
Limitations of the study relate to the age of the data collected between
2000 and 2012, however we believe that our discoveries remain relevant.
PHIS is an administrative database, therefore the patients studied here
were identified utilizing ICD-9 codes, which may not fully reflect all
complications.