Progressive derangement of the T cell compartment in a case of Evans syndrome.
BACKGROUND
Evans syndrome (ES) is a rare disorder characterized by combined autoimmune thrombocytopenia and autoimmune hemolytic anemia. Several studies have documented a number of B cell defects, whereas only limited information is currently available about the T cell subset.


METHODS
A wide panel of immunological analyses aiming specifically at a quantitative and qualitative evaluation of the T cell compartment was performed in an unusual case of ES. The peripheral distribution of the T cell subsets, the diversity of the T cell receptor (TCR) repertoires, the cytokine profile and the T cell apoptosis have been longitudinally evaluated.


RESULTS
On first investigation, flow-cytometric immunophenotyping showed a remarkable alteration of T cell homeostasis with deeply reduced CD4+ naive T cells and recent thymic emigrants. This was seen in association with increased levels of T cell activation and apoptosis. Consistently with these data the cytokine profile was characterized by high interferon-gamma and low interleukin-2 levels. Staining for CD4 and CD25 molecules showed decreased percentages of circulating regulatory T cells according to the autoimmune nature of ES. Finally, restricted TCR repertoires were demonstrated by a skewed TCR beta chain variable (TCRBV) gene usage as well as oligoclonal third complementarity-determining region (CDR3) profiles. A deterioration of the above-mentioned parameters and a worsening of the clinical condition were observed during the follow-up requiring more intensive treatments.


CONCLUSIONS
The demonstration of multiple T cell defects, in addition to providing pathogenetic information, is likely to alter both acute treatment and outcome of ES.
Giovannetti
Antonello
A
Department of Clinical Medicine, Division of Allergy and Clinical Immunology, La Sapienza University, Rome, Italy. antonello.giovannetti@uniroma1.it
Pierdominici
Marina
M
Esposito
Antonella
A
Cagliuso
Maria
M
Stifano
Giuseppina
G
Giammarioli
Anna Maria
AM
Maselli
Angela
A
Malorni
Walter
W
Salsano
Felice
F
Aiuti
Fernando
F
D000293:Adolescent; D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology*; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis / Q000378:metabolism; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D013921:Thrombocytopenia / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D015704:CD4 Antigens; D022801:Complementarity Determining Regions; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma