Does the hyper IgM phenotype affect prognosis in ataxia telangiectasia?

Objective: To evaluate the characteristics of the patients who were followed-up with the diagnosis of ataxia telangiectasia (AT) and to assess the relationship between the hyper IgM (HIGM) phenotype and their prognosis. Materials and Methods: From 2007 to 2019, the study included 68 patients aged 3-35 years who were followed-up with the diagnosis of AT. We retrospectively evaluated the clinical and immunological characteristics and follow-up results. Results: There were 36 girls and 32 boys with a median follow-up of 10 years (1-12 years). The most common complaints upon admission were unsteady walk in 87%, infection in 6%, presence of a family history in 6%, and intracranial mass in 1%. The marriage was consanguineous in 85% of the parents. Ataxia was seen in 100% of the patients, telangiectasia in 97%, and immune deficiency in 88%. Bronchiectasis was observed in 23.5% of the patients, chronic diarrhea in 19%, lymphoproliferation in 15%, malignancy in 10%, autoimmunity in 10%, liver failure in 6%, and granulomatous skin lesions in 6%. Thirteen patients (19%) died during follow-up. The HIGM phenotype was identified in 31% of the patients. Recurrent upper and lower respiratory tract infections (p=0.004 and p<0.0001, respectively), liver failure (p=0.005), and autoimmune diseases (p=0.023) were significantly higher in the HIGM (+) group than the HIGM (-) group. Life expectancy was shorter in the HIGM (+) group with 14 ± 0.73 years (CI 95% 12.55-15.44) compared to the HIGM (-) group with 18 ± 1.64 years (CI 95% 14.77-21.22) (p=0.054). Conclusion: During the early childhood period and before the characteristic findings of AT develop, the patients might present at a hospital with infections, autoimmunity, lymphoproliferation, or malignancy. Physical examination, high alpha-fetoprotein (AFP) levels and immunological testing provide important data for the correct diagnosis. The HIGM phenotype aggravates the clinical course of the disease resulting in fatalities at an earlier age and at a higher rate

IL-12Rβ1 Deficiency in Two of Fifty Children with Severe Tuberculosis from Iran, Morocco, and Turkey

BACKGROUND AND OBJECTIVES: In the last decade, autosomal recessive IL-12Rβ1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rβ1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. METHODS AND PRINCIPAL FINDINGS: We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rβ1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rβ1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. SIGNIFICANCE: This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rβ1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23

Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rß1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, from mucocutaneous candidiasis. Susceptibility to these infections is thought to be due to impairments of IL- 12–dependent IFN-? immunity and IL-23–dependent IL-17A/IL-17F immunity, respectively. We report here patients with autosomal recessive, complete IL- 12Rß2 or IL-23R deficiency, lacking responses to IL-12 or IL- 23 only, all of whom, unexpectedly, display mycobacteriosis without candidiasis. We show that aß T, ?d T, B, NK, ILC1, and ILC2 cells from healthy donors preferentially produce IFN-? in response to IL-12, whereas NKT cells and MAIT cells preferentially produce IFN-? in response to IL-23. We also show that the development of IFN-?–producing CD4+ T cells, including, in particular, mycobacterium-specific TH1* cells (CD45RA-CCR6+), is dependent on both IL-12 and IL-23. Last, we show that IL12RB1, IL12RB2, and IL23R have similar frequencies of deleterious variants in the general population. The comparative rarity of symptomatic patients with IL-12Rß2 or IL-23R deficiency, relative to IL-12Rß1 deficiency, is, therefore, due to lower clinical penetrance. There are fewer symptomatic IL-23R– and IL-12Rß2–deficient than IL-12Rß1–deficient patients, not because these genetic disorders are rarer, but because the isolated absence of IL-12 or IL-23 is, in part, compensated by the other cytokine for the production of IFN-?, thereby providing some protection against mycobacteria. These experiments of nature show that human IL-12 and IL-23 are both required for optimal IFN-?–dependent immunity to mycobacteria, both individually and much more so cooperatively

Effect of White Noise in Relieving Vaccination Pain in Premature Infants

The purpose of this study was to evaluate the effect of white noise as a distraction method in relieving procedural pain caused by vaccination for premature infants. This experimental study was performed at a neonatal intensive care unit (NICU) of a university hospital in Turkey between July and September 2013. The study population was composed of 75 premature infants (35 in the study group and 40 in the control group) who met the inclusion criteria. Premature infants in the study group were exposed to white noise using MP3 players placed at the head of the infants' open crib for 1 minute before vaccination. The white noise continued until 1 minute after vaccination. Premature infants in the control group were not exposed to white noise. The Premature Infant Information Form, Intervention Follow-up Form, and Premature Infant Pain Profile (PIPP) were used to collect study data. Descriptive statistics, chi-square test, and independent sample t-tests were used to evaluate the data. The pain level of the control group (PIPP = 14.35 +/- 2.59) was significantly higher than the pain level of the study group (PIPP = 8.14 +/- 3.14) (p < .05). The authors found that 67.6% of the infants in the study group had moderate pain during vaccination and only 2.9% had severe pain. Most of the infants in the control group (82.5%) had severe pain, whereas 17.5% had moderate pain (p < .05). White noise was found to be effective for this sample; however, there is a dire need for extensive research on white noise and its use with this vulnerable population. (C) 2016 by the American Society for Pain Management Nursin

The evaluation of malignancies in Turkish PID patients; A multicenter study

WOS: 00043131160017