Clinical, immunologic and genetic profiles of DOCK8-deficient patients in Kuwait

Waleed Al-Herz 1, Raj Ragupathy, Michel J Massaad, Raja'a Al-Attiyah, Arti Nanda, Karin R Engelhardt, Bodo Grimbacher, Luigi Notarangelo, Talal Chatila, Raif S Geha

Affiliations

01 June 2012

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doi: 10.1016/j.clim.2012.03.002

Abstract

Deficiency of dedicator of cytokinesis 8 (DOCK8) is a newly described combined primary immunodeficiency disease. It was found to account for 15% of combined immune deficiency cases in the National Primary Immunodeficiency Disorders Registry in Kuwait, a country with high prevalence of consanguinity. We present the clinical, immunologic and molecular characteristics of 9 Kuwaiti patients with DOCK8 deficiency and discuss differences that distinguish DOCK8 deficiency from atopic dermatitis. Clinical immunologists in areas with high incidence of consanguinity should have a high index of suspicion of DOCK8 deficiency in children with recalcitrant eczema, recurrent non-cutaneous infections and lymphopenia.

Figures

Figure 1 A. Patient A54 with perioral dermatitis and diffuse hypermelanosis of oral mucosa B. Oral mucosal biopsy shows acanthotic epithelium (A). In the subepithelium there are large number of melanophages (white arrow) admixed with chronic mixed inflammatory cell infiltrate (yellow arrow) (H.E. × 20).

Figure 1 A. Patient A54 with perioral dermatitis and diffuse hypermelanosis of oral mucosa B. Oral mucosal biopsy shows acanthotic epithelium (A). In the subepithelium there are large number of melanophages (white arrow) admixed with chronic mixed inflammatory cell infiltrate (yellow arrow) (H.E. × 20).

Figure 2 DOCK8 deficiency impairs T cell activation. T-lymphocyte proliferative responses using both PHA and anti-CD-3 in patients and controls (n = 5/group).

Figure 2 DOCK8 deficiency impairs T cell activation. T-lymphocyte proliferative responses using both PHA and anti-CD-3 in patients and controls (n = 5/group).

Figure 3 Cytokine levels in the culture supernatants. PBMC from the patients secreted significantly lower amounts of IL-2, TNF-α and IFN-γ than those from healthy controls in response to stimulation with PHA (Mean & 95% Confidence Intervals) (n = 5/group)

Figure 3 Cytokine levels in the culture supernatants. PBMC from the patients secreted significantly lower amounts of IL-2, TNF-α and IFN-γ than those from healthy controls in response to stimulation with PHA (Mean & 95% Confidence Intervals) (n = 5/group)

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