The lower serum immunoglobulin G2 level in severe cases than in mild cases of pandemic H1N1 2009 influenza is associated with cytokine dysregulation.
The majority of patients with pandemic influenza H1N1 2009 had mild illness, but some, including those with no risk factors for severe disease, may succumb to this infection. Besides viral factors such as the D222/225G substitution of the hemagglutinin, host factors such as IgG2 subclass deficiency recently was reported to be associated with severe disease in a cohort of Australian patients besides other known risk factors, including underlying chronic illness, extremes of age, and pregnancy. We conducted a case-control study of 38 Asian patients with respiratory failure due to severe pandemic influenza and compared the results to those for 36 mild cases. None had selective IgG2 deficiency, but the level of IgG2 subclass was significantly lower in the severe cases (3.55 g/liter versus 4.75 g/liter; P = 0.002), whereas the levels of IgG1, IgG3, and IgG4 were not significantly different from those of the mild cases. Previous studies suggested that some IgHG2 and FcγRIIa genotypes were associated with IgG2 deficiency. The allelic frequency of the IgHG2 genotypes in our severe cases was not correlated with their levels of IgG2, while that of FcγRIIa was not significantly different from that of the general Han Chinese population (P = 0.216). Only the overall cytokine/chemokine profile (P = 0.029) and serum globulin level (P = 0.005) were found to be independently associated with the IgG2 level by multivariate analysis. The lower IgG2 level in our severe group might be related to cytokine dysregulation rather than being a significant risk factor for severe pandemic influenza. The importance of this finding for therapeutic intervention will require further studies of larger cohorts of patients.
Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Jasper Fuk-Woo
JF
Chan
Kelvin Kai-Wang
KK
To
Herman
H
Tse
Candy Choi-Yi
CC
Lau
Iris Wai-Sum
IW
Li
Ivan Fan-Ngai
IF
Hung
Kwok-Hung
KH
Chan
Vincent Chi-Chung
VC
Cheng
Thomas Sik-To
TS
Lai
Patrick Chiu-Yat
PC
Woo
Eric Yuk-Tat
EY
Chan
Kwok-Yung
KY
Yuen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood*; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007251:Influenza, Human / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D012720:Severity of Illness Index
D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G