Diagnóstico de inmunodeficiencias primarias basado en citometría de flujo

 Primary immunodeficiencies (PIDs): heterogeneous group of monogenetic disorders of the

immune system  resulting in recurrent and/or severe infections, autoimmunity,
autoinflammation, or malignancies
 Difficult diagnosis of PIDs: spectrum of PIDs is expanding  difficult to diagnose based on
clinical and conventional laboratory findings alone.
 Genetic analysis: definite diagnosis of PID (high time and cost)  flow cytometry: rapid and
highly sensitive tool for diagnosis.
 Flow cytometry: bridge between conventional immunological testing and DNA sequencing
(rapid and accurate results based on single cell analysis).
 Función de citometría de flujo: evaluation of specific cell populations and subpopulations,
cell surface, intracellular and intranuclear proteins, biologic effects of specific immune
defects, and functional immune characteristics  diagnosis and evaluation of PIDs.
 Formas más comunes de PIDs:
o Severe combined immunodeficiency (SCID): lack of T cells (impact on B and NK cells is
variable depending on the genetic defect)
o X-linked SCID (X-SCID): deficient CD132 (common g chain) expression
o X-linked agammaglobulinemia (XLA): absence of B cells in the peripheral blood,
lack of Bruton's tyrosine kinase (BTK) expression in monocytes and platelets
o X-linked hyper IgM syndrome (XHIGM): fail to express CD40 ligand (CD40L) on
activated T cells, and a group of patients with autosomal recessive syndrome lack
CD40 expression on B cells
o Common variable immunodeficiency (CVID): characterized by assessing CD19+ B
cells, B-cell activating factor receptor (BAFF-R) on B cells, and the inducible co-
stimulator (ICOS) on activated T cells
o Hyper IgE syndrome (HIES): decreased number of circulating T helper (Th)17 cells
o Wiskott-Aldrich syndrome
o X-linked lymphoproliferative syndrome (XLP): decrease in invariant natural killer T
(iNKT) cells
o Familial hemophagocytic lymphohistiocytosis
o Autoimmune lymphoproliferative syndrome (ALPS): increased T-cell receptor (TCR)-a/b-
positive double-negative T (DNT) cells
o IPEX syndrome
o CTLA 4 haploinsufficiency and LRBA deficiency
o IRAK4 and MyD88 deficiencies
o Mendelian susceptibility to mycobacterial disease (MSMD): aberrant interferon
(IFN)-gR1 expression on monocytes or deficient IL12Rb1 expression on activated T
cells
o Leukocyte adhesion deficiency type 1 (LAD1): absent expression of CD18 on
granulocytes
o Chronic mucocuneous candidiasis (CMCD): decreased number of circulating T
helper (Th)17 cells  lack of IL-17RA expression on lymphocytes and monocytes
o Chronic granulomatous disease (CGD): gp91-phox- and p22-phox-deficient  lack
of membrane bound cytochrome b558
Application of flow cytometry in the diagnosis of PIDs