Deficiency in circulating natural killer (NK) cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia

Abstract

SUMMARYAbsolute and relative NK cell numbers were determined in peripheral whole blood by flow cytometry in patients with common variable immunodeficiency (CVID) (n 55) and X-linked agammaglobulinaemia (XLA) (n 19) on regular immunoglobulin (IVIG) therapy. Absolute CD3 2 CD16 1 NK cell numbers were significantly reduced in CVID patients (median 108/ml, range 23±815), compared with normal subjects (n 60) (289/m l, range 56±640, P , 0´001). Total lymphocyte concentrations were significantly lower in CVID (median 1587/ml, range 523±7519) compared with normal subjects (median 2019/ml, range 1124±3149, P 0´004), with the percentage of NK cells also being significantly decreased (median 7´5%, range 3´0±33´0%, compared with 14´2%, range 2´6±30´8%, P , 0´001). In XLA, absolute NK cell numbers (median 140/ml, range 32±551, P , 0´001) but not relative numbers were significantly reduced compared with normal controls. We excluded the possibility that IVIG interferes with in vitro binding of CD16 MoAbs. Further analysis of NK cell subsets showed a deficiency of both CD16 1 and CD56 1 cells in CVID, most marked in the CD3 2 CD8 dim subpopulation, which may be due to increased homing of these cells to the gut. Serial studies on a small number of patients suggest that IVIG therapy has no short-term effect on NK cells, although we cannot exclude an effect with prolonged use. Although there are no obvious clinical effects of the NK depletion in CVID and XLA, this may be a factor in their predisposition to cancer.Keywords natural killer cells CD16 common variable immunodeficiency X-linked agammaglobulinaemia intravenous immunoglobulin therapy interferon-gamma

Immunomodulatory action of intravenous immunoglobulin

“…High-dose IVIg has no discernible effect on natural killer cell IFN-g expression following stimulation with PMA and ionomycin 47 nor on monocyte IL-12 expression. 48 Soluble cytokine receptors such as TNF-receptors increase following IVIg infusion, and there is a considerable increase (1000-fold molar excess) in IL-1Ra levels.…”

Fine-Scale Mapping at IGAD1 and Genome-Wide Genetic Linkage Analysis Implicate HLA-DQ/DR as a Major Susceptibility Locus in Selective IgA Deficiency and Common Variable Immunodeficiency

“…In fact, several genes in the region have been implicated in humoral immune responses, including CD38 and CD157 (Table IV). A putative locus at 12p, which shows association/suggestive linkage in other autoimmune disorders (77), contains the NK gene complex, and thus is of interest since NK cell abnormalities have been reported in CVID (78). A proposal linking IL-10 to the granulomatous form of CVID (79) may gain support from the NPL scores at 1q31-q32 (Fig.…”

Inmunodeficiencia común variable: caracterización clínica e inmunológica de pacientes y definición de subgrupos homogéneos con base en la tipificación de subpoblaciones de linfocitos B

“…Además, en cuatro pacientes observamos una reducción en el número total de los linfocitos NK, un hallazgo común en la inmunodeficiencia común variable, la cual, según se postula, resultaría de una permanencia prolongada de estas células en el intestino de algunos pacientes, lo que, a su vez, reduciría su frecuencia en la circulación periférica (45).…”