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T-cell activation discriminates subclasses of symptomatic primary humoral immunodeficiency diseases in adults.

Picat MQ, Thiébaut R, Lifermann F, Delbrel X, Adoue D, Wittkop L, Fauchais AL, Rispal P, Moreau JF, Viallard JF - BMC Immunol. (2014)

Bottom Line: Symptomatic Primary Humoral Immunodeficiency Diseases (PHID) constitute a highly heterogeneous group of diseases characterized by a shared hypogammaglobulinemia, resulting in increased risk of recurrent or severe infections.Combining the set of markers involved in PHID supported the existence of two distinct mechanisms associated with complications.These results highlight the importance of T-cell activation that may improve discrimination of PHID patients in specific subgroups and help to identify patients with different clinical outcomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux F-33076, France. rodolphe.thiebaut@isped.u-bordeaux2.fr.

ABSTRACT

Background: Symptomatic Primary Humoral Immunodeficiency Diseases (PHID) constitute a highly heterogeneous group of diseases characterized by a shared hypogammaglobulinemia, resulting in increased risk of recurrent or severe infections. Associations have been described with a variety of immunological abnormalities involving B and T-cell differentiation, T-cell activation and innate immunity. However, PHID discrimination remains based on B-lymphocyte abnormalities and other components of the immune system have not been sufficiently taken into account. We carried out unsupervised and supervised methods for classification in a cohort of 81 symptomatic PHID patients to evaluate the relative importance of 23 immunological parameters and to select relevant markers that may be useful for diagnosis and prognosis.

Results: We identified five groups of patients, among which the percentage of PHID complications varied substantially. Combining the set of markers involved in PHID supported the existence of two distinct mechanisms associated with complications. Switched memory B-cell attrition and CD8+ HLA-DR + activated T-cell increase were the prominent abnormalities observed in PHID complications. Furthermore, in a subgroup of 57 patients with common variable immunodeficiency, the classification that added CD8+ HLA-DR + to the consensual EUROclass classification was better than the EUROclass model in predicting complications.

Conclusion: These results highlight the importance of T-cell activation that may improve discrimination of PHID patients in specific subgroups and help to identify patients with different clinical outcomes.

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Related in: MedlinePlus

23 immunological markers involved in PHID, plotted on the first two Principal Components (PC). ALTADIH Cohort, 2007-2010. Immunological markers are well represented by the component when they are far from the center and close to the corresponding axis. Two markers are: 1) positively correlated if close to each other; 2) not correlated if in a rectangular position; 3) negatively correlated if on the opposite side.
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Figure 1: 23 immunological markers involved in PHID, plotted on the first two Principal Components (PC). ALTADIH Cohort, 2007-2010. Immunological markers are well represented by the component when they are far from the center and close to the corresponding axis. Two markers are: 1) positively correlated if close to each other; 2) not correlated if in a rectangular position; 3) negatively correlated if on the opposite side.

Mentions: Principal Component Analysis (PCA) is an unsupervised dimension-reduction method that generates Principal Components (PC), that are linear combinations of the original variables[25] (in our case, represented by differentiation, activation and regulation markers of B and T-lymphocytes, natural killer cells, dendritic cells and T-cells expressing a gamma/delta TCR). Each component explains a part of the variability of the data. We used 2D plots to project data on the plane spanned by the first two components to display 23 immunological markers involved in PHID (missing data excluded). As data run in the principal component analysis have been normalized as referred to the sample (minus sample mean and divided by standard deviation), data are presented on a unit correlation circle of radius 1 (see Figure 1). Because each component is a weighted linear combination of the original variables, a component may have a meaning according to the contribution of each immunological marker. We chose to present the plan spanned by the two major principal components because they explained the most, variability of data (> 10%). On this plan, the contribution of markers is unequal and depends on the contribution of each marker on each axis. A given marker may contribute on the third axis and therefore would not be well represented on the first two axes. PCA was also performed in CVID patients. A PCA on markers of 12 healthy donors is given in Additional file3: Figure S2.


T-cell activation discriminates subclasses of symptomatic primary humoral immunodeficiency diseases in adults.

Picat MQ, Thiébaut R, Lifermann F, Delbrel X, Adoue D, Wittkop L, Fauchais AL, Rispal P, Moreau JF, Viallard JF - BMC Immunol. (2014)

23 immunological markers involved in PHID, plotted on the first two Principal Components (PC). ALTADIH Cohort, 2007-2010. Immunological markers are well represented by the component when they are far from the center and close to the corresponding axis. Two markers are: 1) positively correlated if close to each other; 2) not correlated if in a rectangular position; 3) negatively correlated if on the opposite side.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4008268&req=5

Figure 1: 23 immunological markers involved in PHID, plotted on the first two Principal Components (PC). ALTADIH Cohort, 2007-2010. Immunological markers are well represented by the component when they are far from the center and close to the corresponding axis. Two markers are: 1) positively correlated if close to each other; 2) not correlated if in a rectangular position; 3) negatively correlated if on the opposite side.
Mentions: Principal Component Analysis (PCA) is an unsupervised dimension-reduction method that generates Principal Components (PC), that are linear combinations of the original variables[25] (in our case, represented by differentiation, activation and regulation markers of B and T-lymphocytes, natural killer cells, dendritic cells and T-cells expressing a gamma/delta TCR). Each component explains a part of the variability of the data. We used 2D plots to project data on the plane spanned by the first two components to display 23 immunological markers involved in PHID (missing data excluded). As data run in the principal component analysis have been normalized as referred to the sample (minus sample mean and divided by standard deviation), data are presented on a unit correlation circle of radius 1 (see Figure 1). Because each component is a weighted linear combination of the original variables, a component may have a meaning according to the contribution of each immunological marker. We chose to present the plan spanned by the two major principal components because they explained the most, variability of data (> 10%). On this plan, the contribution of markers is unequal and depends on the contribution of each marker on each axis. A given marker may contribute on the third axis and therefore would not be well represented on the first two axes. PCA was also performed in CVID patients. A PCA on markers of 12 healthy donors is given in Additional file3: Figure S2.

Bottom Line: Symptomatic Primary Humoral Immunodeficiency Diseases (PHID) constitute a highly heterogeneous group of diseases characterized by a shared hypogammaglobulinemia, resulting in increased risk of recurrent or severe infections.Combining the set of markers involved in PHID supported the existence of two distinct mechanisms associated with complications.These results highlight the importance of T-cell activation that may improve discrimination of PHID patients in specific subgroups and help to identify patients with different clinical outcomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux F-33076, France. rodolphe.thiebaut@isped.u-bordeaux2.fr.

ABSTRACT

Background: Symptomatic Primary Humoral Immunodeficiency Diseases (PHID) constitute a highly heterogeneous group of diseases characterized by a shared hypogammaglobulinemia, resulting in increased risk of recurrent or severe infections. Associations have been described with a variety of immunological abnormalities involving B and T-cell differentiation, T-cell activation and innate immunity. However, PHID discrimination remains based on B-lymphocyte abnormalities and other components of the immune system have not been sufficiently taken into account. We carried out unsupervised and supervised methods for classification in a cohort of 81 symptomatic PHID patients to evaluate the relative importance of 23 immunological parameters and to select relevant markers that may be useful for diagnosis and prognosis.

Results: We identified five groups of patients, among which the percentage of PHID complications varied substantially. Combining the set of markers involved in PHID supported the existence of two distinct mechanisms associated with complications. Switched memory B-cell attrition and CD8+ HLA-DR + activated T-cell increase were the prominent abnormalities observed in PHID complications. Furthermore, in a subgroup of 57 patients with common variable immunodeficiency, the classification that added CD8+ HLA-DR + to the consensual EUROclass classification was better than the EUROclass model in predicting complications.

Conclusion: These results highlight the importance of T-cell activation that may improve discrimination of PHID patients in specific subgroups and help to identify patients with different clinical outcomes.

Show MeSH
Related in: MedlinePlus