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2016 ; 213
(7
): 1180-8
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Whole-Exome Sequencing Reveals Mutations in Genes Linked to Hemophagocytic
Lymphohistiocytosis and Macrophage Activation Syndrome in Fatal Cases of H1N1
Influenza
#MMPMID26597256
Schulert GS
; Zhang M
; Fall N
; Husami A
; Kissell D
; Hanosh A
; Zhang K
; Davis K
; Jentzen JM
; Napolitano L
; Siddiqui J
; Smith LB
; Harms PW
; Grom AA
; Cron RQ
J Infect Dis
2016[Apr]; 213
(7
): 1180-8
PMID26597256
show ga
BACKGROUND: Severe H1N1 influenza can be lethal in otherwise healthy individuals
and can have features of reactive hemophagocytic lymphohistiocytosis (HLH). HLH
is associated with mutations in lymphocyte cytolytic pathway genes, which have
not been previously explored in H1N1 influenza. METHODS: Sixteen cases of fatal
influenza A(H1N1) infection, 81% with histopathologic hemophagocytosis, were
identified and analyzed for clinical and laboratory features of HLH, using
modified HLH-2004 and macrophage activation syndrome (MAS) criteria. Fourteen
specimens were subject to whole-exome sequencing. Sequence alignment and variant
filtering detected HLH gene mutations and potential disease-causing variants.
Cytolytic function of the PRF1 p.A91V mutation was tested in
lentiviral-transduced NK-92 natural killer (NK) cells. RESULTS: Despite several
lacking variables, cases of influenza A(H1N1) infection met 44% and 81% of
modified HLH-2004 and MAS criteria, respectively. Five subjects (36%) carried one
of 3 heterozygous LYST mutations, 2 of whom also possessed the p.A91V PRF1
mutation, which was shown to decrease NK cell cytolytic function. Several
patients also carried rare variants in other genes previously observed in MAS.
CONCLUSIONS: This cohort of fatal influenza A(H1N1) infections confirms the
presence of hemophagocytosis and HLH pathology. Moreover, the high percentage of
HLH gene mutations suggests they are risk factors for mortality among individuals
with influenza A(H1N1) infection.