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

Marie-Quitterie Picat 1, 2, 3 Rodolphe Thiébaut 1, 2, 3, * François Lifermann 4 Xavier Delbrel 5 Daniel Adoue 6 Linda Wittkop 1, 2, 3 Anne-Laure Fauchais 7 Patrick Rispal 8 Jean-François Moreau 9 Jean-François Viallard 10, *
* Corresponding author
1 Service d'Informations Médicales
2 Epidémiologie et Biostatistique [Bordeaux]
3 SISTM - Statistics In System biology and Translational Medicine
Epidémiologie et Biostatistique [Bordeaux], Inria Bordeaux - Sud-Ouest
4 Service de Médecine Interne [Dax]
5 Service de Médecine Interne [Pau]
6 Service de Médecine Interne [Purpan]
7 Service de Médecine interne A et polyclinique médicale [CHU Limoges]
8 Service de Médecine Interne [Agen]
9 CIRID - Composantes innées de la réponse immunitaire et différenciation
10 Service de Médecine Interne et Maladies Infectieuses [Pessac]
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.
Keywords : Symptomatic primary humoral immunodeficiency T-cell activation HLA-DR marker Hierarchical clustering Principal component analysis Common variable immunodeficiency IgG subclass deficiency Good ' s syndrome
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Journal articles
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Submitted on : Tuesday, April 22, 2014 - 5:36:48 AM
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Marie-Quitterie Picat, Rodolphe Thiébaut, François Lifermann, Xavier Delbrel, Daniel Adoue, et al.. T-cell activation discriminates subclasses of symptomatic primary humoral immunodeficiency diseases in adults.. BMC Immunology, BioMed Central, 2014, 15 (1), pp.13. ⟨10.1186/1471-2172-15-13⟩. ⟨inserm-00981320⟩

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