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Immune Repertoire Diversity Correlated with Mortality in Avian Influenza A (H7N9) Virus Infected Patients

View Article: PubMed Central - PubMed

ABSTRACT

Specific changes in immune repertoires at genetic level responding to the lethal H7N9 virus are still poorly understood. We performed deep sequencing on the T and B cells from patients recently infected with H7N9 to explore the correlation between clinical outcomes and immune repertoire alterations. T and B cell repertoires display highly dynamic yet distinct clonotype alterations. During infection, T cell beta chain repertoire continues to contract while the diversity of immunoglobulin heavy chain repertoire recovers. Patient recovery is correlated to the diversity of T cell and B cell repertoires in different ways – higher B cell diversity and lower T cell diversity are found in survivors. The sequences clonally related to known antibodies with binding affinity to H7 hemagglutinin could be identified from survivors. These findings suggest that utilizing deep sequencing may improve prognostication during influenza infection and could help in development of antibody discovery methodologies for the treatment of virus infection.

No MeSH data available.


Shared TRB CDR3 sequences expressed at different levels between survivors and non-survivors.Comparison of the expression level of the shared sequences was performed using Wilcoxon Test, and the representative sequences expressed significantly different between survivors and non-survivors were drawn (p < 0.05). Each Colum is for one patient and the annotation bar represents the outcome of the patient (green for non-survival group, purple for survival group). Color of each rectangle stands for logged reads of the clone noted at right sided of the panel (blue as lowest, red as highest).
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f5: Shared TRB CDR3 sequences expressed at different levels between survivors and non-survivors.Comparison of the expression level of the shared sequences was performed using Wilcoxon Test, and the representative sequences expressed significantly different between survivors and non-survivors were drawn (p < 0.05). Each Colum is for one patient and the annotation bar represents the outcome of the patient (green for non-survival group, purple for survival group). Color of each rectangle stands for logged reads of the clone noted at right sided of the panel (blue as lowest, red as highest).

Mentions: We compared the sequence identity of IGH CDR3s in response to H7N9 across different individuals. Overlap between different patients was very limited, even in intergroup pairs (data not shown). In addition, we failed in identifying any IGH sequences differently expressed in two groups. However, we found some TRB, IGL and IGK CDR3 sequences shared among most of the patients. Interestingly, survivors shared many TRB CDR3 sequences that found to be absent or expressed at a much lower level in non-survivors (p < 0.05) (Fig. 5). These shared sequences in TRB were predominately not dominant clones but of high similarity, which indicates that these sequences may have similar function and are related to recovery from infection. For IGK and IGL, patients with different prognosis expressed comparably high level of same or similar CDR3 sequences, including dominant clones (Supplementary Figure S6).


Immune Repertoire Diversity Correlated with Mortality in Avian Influenza A (H7N9) Virus Infected Patients
Shared TRB CDR3 sequences expressed at different levels between survivors and non-survivors.Comparison of the expression level of the shared sequences was performed using Wilcoxon Test, and the representative sequences expressed significantly different between survivors and non-survivors were drawn (p < 0.05). Each Colum is for one patient and the annotation bar represents the outcome of the patient (green for non-survival group, purple for survival group). Color of each rectangle stands for logged reads of the clone noted at right sided of the panel (blue as lowest, red as highest).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037391&req=5

f5: Shared TRB CDR3 sequences expressed at different levels between survivors and non-survivors.Comparison of the expression level of the shared sequences was performed using Wilcoxon Test, and the representative sequences expressed significantly different between survivors and non-survivors were drawn (p < 0.05). Each Colum is for one patient and the annotation bar represents the outcome of the patient (green for non-survival group, purple for survival group). Color of each rectangle stands for logged reads of the clone noted at right sided of the panel (blue as lowest, red as highest).
Mentions: We compared the sequence identity of IGH CDR3s in response to H7N9 across different individuals. Overlap between different patients was very limited, even in intergroup pairs (data not shown). In addition, we failed in identifying any IGH sequences differently expressed in two groups. However, we found some TRB, IGL and IGK CDR3 sequences shared among most of the patients. Interestingly, survivors shared many TRB CDR3 sequences that found to be absent or expressed at a much lower level in non-survivors (p < 0.05) (Fig. 5). These shared sequences in TRB were predominately not dominant clones but of high similarity, which indicates that these sequences may have similar function and are related to recovery from infection. For IGK and IGL, patients with different prognosis expressed comparably high level of same or similar CDR3 sequences, including dominant clones (Supplementary Figure S6).

View Article: PubMed Central - PubMed

ABSTRACT

Specific changes in immune repertoires at genetic level responding to the lethal H7N9 virus are still poorly understood. We performed deep sequencing on the T and B cells from patients recently infected with H7N9 to explore the correlation between clinical outcomes and immune repertoire alterations. T and B cell repertoires display highly dynamic yet distinct clonotype alterations. During infection, T cell beta chain repertoire continues to contract while the diversity of immunoglobulin heavy chain repertoire recovers. Patient recovery is correlated to the diversity of T cell and B cell repertoires in different ways &ndash; higher B cell diversity and lower T cell diversity are found in survivors. The sequences clonally related to known antibodies with binding affinity to H7 hemagglutinin could be identified from survivors. These findings suggest that utilizing deep sequencing may improve prognostication during influenza infection and could help in development of antibody discovery methodologies for the treatment of virus infection.

No MeSH data available.