Regulatory natural killer cell expression in atopic childhood asthma

Introduction: Different subsets of natural killer (NK) cells were found to play a role in pathogenesis of allergy. We sought to investigate the expression of regulatory NK cells (CD56+CD16+CD158+) in atopic children with bronchial asthma in order to outline the value of these cells as biomarkers of disease severity and/or control.Methods: A cross sectional controlled study was carried out in the Pediatric Allergy and Immunology Unit, Ain Shams University. The study included 45 atopic children [mean age(SD)= (2.9) years] with bronchial asthma (BA) and/or allergic rhinitis (AR)as well as 40 healthy matched controls. Enrolled subjects underwent complete blood counting and flow cytometric measurement of NK cell (CD16+ CD56+) and regulatory NK cells (CD16+CD56+CD158+).Results: Patients had significantly higher regulatory NK cell percentages [mean (SD)= 41 (52) %] than controls [mean (SD)=15 (7.1)]; p≤0.001. Regulatory NK cell counts and percentages did not vary with the concomitant presence of AR or the degree of asthma control. Regulatory NK cell counts tended to be higher in children with moderate/severe BA compared to those with mild asthma but the difference did not reach statistical significance (U= -1.8, p=0.06). NK cell counts [mean (SD)= 159 (164) cells/μl] and percentages [mean (SD)= 3.7 (3.2) %] were comparable among patients and controls and did not vary with the presence of AR (p= 0.51, 0.95) or with the degree of asthma control. NK cells absolute counts and percentages tended to be higher among patients with moderate/severe compared to mild asthma but the difference did not reach statistical significance.Conclusions: Regulatory NK cells seem to be increased in childhood asthma. We recommend wider scale prospective studies on steroid-naïve subjects involving measurement of cytokines that are secreted by different types of NK cells.Keywords: Natural killer, regulatory, asthma, children, allerg

Characterizing the morbid genome of ciliopathies

Background Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete. Results We applied genomic approaches on a large patient cohort of 371 affected individuals from 265 families, with phenotypes that span the entire ciliopathy spectrum. Likely causal mutations in previously described ciliopathy genes were identified in 85% (225/265) of the families, adding 32 novel alleles. Consistent with a fully penetrant model for these genes, we found no significant difference in their “mutation load” beyond the causal variants between our ciliopathy cohort and a control non-ciliopathy cohort. Genomic analysis of our cohort further identified mutations in a novel morbid gene TXNDC15, encoding a thiol isomerase, based on independent loss of function mutations in individuals with a consistent ciliopathy phenotype (Meckel-Gruber syndrome) and a functional effect of its deficiency on ciliary signaling. Our study also highlighted seven novel candidate genes (TRAPPC3, EXOC3L2, FAM98C, C17orf61, LRRCC1, NEK4, and CELSR2) some of which have established links to ciliogenesis. Finally, we show that the morbid genome of ciliopathies encompasses many founder mutations, the combined carrier frequency of which accounts for a high disease burden in the study population. Conclusions Our study increases our understanding of the morbid genome of ciliopathies. We also provide the strongest evidence, to date, in support of the classical Mendelian inheritance of Bardet-Biedl syndrome and other ciliopathies