Relationship Between Severity of T Cell Lymphopenia and Immune Dysregulation in Patients with DiGeorge Syndrome (22q11.2 Deletions and/or Related TBX1 Mutations): a USIDNET Study.

PURPOSE: DiGeorge syndrome has substantial heterogeneity with variable immune deficiency and dysregulation. Implicated immunopathology includes reduced thymic output and increased peripheral homeostatic proliferation with Th2 skewing and expansion of self-reactive cells. We hypothesized that T cell lymphopenia severity will be associated with higher odds of autoimmunity and/or asthma. METHODS: Using the US Immunodeficiency Network registry, we identified patients with 22q11.2 deletion (and/or TBX1). Initial absolute CD3+ T cell values were stratified: normal, 50-99% and below 50% of the lower limit of age-adjusted normal values. Patients with and without reported autoimmunity and asthma were compared using chi-square tests and multivariate logistic regression. RESULTS: Among 415 patients, autoimmunity was reported in 17 (4.1%), and asthma was reported in 28 (6.7%). Compared with those with no reported autoimmunity, patients with reported autoimmunity more frequently had low CD19+ B cells [3.3% (12/364) vs 28.6% (4/14); p = 0.002] and low IgG [6.2% (20/321) vs 29.4% (5/17); p = 0.005] levels. There were no statistically significant differences in other immune characteristics among those with and without reported asthma. Patients with absolute CD3 levels below 50% of age-adjusted normal values had higher odds of reported autoimmunity (n = 319, OR = 7.56, 95% CI = 1.58-36.17, p = 0.01) and reported asthma (n = 319, OR = 4.5, 95% CI = 1.06-18.93, p = 0.04) as compared with those with normal CD3 values, adjusted for age and low IgG. CONCLUSIONS: Absolute CD3+ T cell counts below 50% of age-adjusted normal values may be associated with higher odds of autoimmunity and/or asthma in patients with DiGeorge syndrome and be potentially useful to identify higher-risk patients.

CARMIL2-related immunodeficiency manifesting with photosensitivity.

We report a case of a newly recognized primary immunodeficiency due to biallelic mutations in CARMIL2 manifesting as an actinic prurigo-like photodermatitis, allergic diathesis and recurrent infections in a child. We present this case to highlight a rare phenotype seen in this T-cell immunodeficiency and provide an overview of other dermatologic manifestations among published reports of this condition.

Direct measurement of upper airway inflammation in children with chronic rhinosinusitis: implications for asthma.

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a common heterogenous multifactorial disorder affecting children and adults. The exact mechanism is not completely understood. In this review, we aim to summarize our recent findings regarding etiologies and pathogenesis of CRS in children and review recent studies investigating inflammatory patterns in the upper airways in children and adults with CRS. RECENT FINDINGS: There are only a few small studies measuring upper airway inflammation in children with CRS. These studies demonstrated more toward eosinophilic and T-cell driven inflammatory pattern. Cytokine patterns in upper airways seem to correlate with asthma symptoms in children with CRS. Adult studies demonstrate eosinophilic and Th-2 (T helper-1) driven inflammation in CRS with nasal polyps and Th-1 (T helper-2) driven inflammation in CRS without nasal polyps. SUMMARY: Current knowledge about the characteristics of tissue inflammation in upper airways in children with CRS is limited. More studies are needed to better understand the pathogenesis and better define the subgroups of CRS. The findings of such studies will lead to identifying the biological targets to treat this condition.