Epithelial Barrier Hypothesis and Its Comparison with the Hygiene Hypothesis

Chronic inflammatory conditions including allergic, autoimmune, metabolic, and neuropsychiatric disorders are constantly increasing and leading to a high burden, especially in more industrialized countries. The prevalence is still on the rise in developing countries. The start of the steep increase in asthma, atopic dermatitis, and allergic rhinitis dates to the 1960s, whereas a second wave with an increase in eosinophilic gastrointestinal disease, food allergy, and drug hypersensitivity started after the 2000s. These diseases also started to appear more with neuropsychiatric and autoimmune conditions during the last few decades. Many theories have been proposed to explain this outbreak. The hygiene hypothesis was consolidated by "old friends" and biodiversity, although some gaps remained unresolved. The introduction of the epithelial barrier hypothesis gave us a new perspective to explain the effects of industrialization without environment control and health concerns creeping into our daily lives. The present review touches on the possible explanations of why epithelial barrier hypothesis covers all previous ones, which are not contradictory but mostly complementary

Impaired IL-23-dependent induction of IFN-gamma underlies mycobacterial disease in patients with inherited TYK2 deficiency

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-alpha/beta (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-gamma is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.ANRS Nord-Sud ; CIBSS ; CODI ; Comité para el Desarrollo de la Investigación ; Fulbright Future Scholarshi

Can Atopic Diseases be Differentiated from Hyper IgE Syndromeby Serum IgE and Blood Eosinophil Levels?

Giriş: Yüksek serum IgE ve eozinofil değerleri ağır atopik dermatit, persistan gıda allerjileri ve tedavisi zor allerjik astımın olduğu kadar Hiper IgE sendromu (HİES) başta olmak üzere bazı primer immün yetmezliklerin de laboratuvar bulgularıdır. Çalışmamızda, IgE yüksekliği ile seyreden kronik granülomatöz hastalık ve HİES tanılı hastalar ile atopik dermatit, IgE aracılı gıda allerjisi, allerjik astım ve/ veya rinitli çocukların IgE ve eozinofil değerlerini, duyarlanmalarını karşılaştırarak atopik hastalıklar ile immün yetmezlik hastalıklarını ayırt etmede bir kesim değeri bulmayı hedefledik. Gereç ve Yöntem: Toplam 315 hasta çalışmaya alındı. Hastaların serum IgE (IU/L) ve eozinofil (/mm3) değerleri, duyarlanmaları ve yaşları değerlendirildi. ROC analizi ile IgE ve eozinofil seviyeleri için ideal kesim değeri hesaplandı. Bulgular: Primer immün yetmezlik grubunda IgE ortanca değeri 2542 (min:1, maks:55400), eozinofil ortanca değeri 1000 (min:0, maks:37880), atopi grubunda ise IgE ortanca değeri 265 (min:4, maks:7122), eozinofil ortanca değeri ise 400 (min:0, maks: 6050) hesaplandı. Gruplar karşılaştırıldığında IgE ve eozinofil değerleri primer immün yetmezlik grubunda atopiklere göre anlamlı derecede yüksekti (her ikisi için p0.001). Allerjenlerin etkisi karşılaştırıldığında gıda allerjenlerine duyarlanmış hastalarda sadece ev tozu akarı ve/veya ot poleni duyarlılara göre IgE anlamlı yüksekti (sırasıyla p0.008, p0.01). HİES tanısı için kesim değeri IgE2000 IU/l alındığında duyarlılık %74, özgünlük %96 (PPD: %74, NPD: %96), IgE5000 IU/l için duyarlılık %56, özgünlük %99 (PPD: %91, NPD: %94), eozinofil1500/mm3 alındığında duyarlılık %51, özgünlük %96 (PPD: %61, NPD: %93), eozinofil2500/mm3 için duyarlılık %41, özgünlük %98 (PPD: %76, NPD: %92) olarak belirlendi. Sonuç: ROC analizinde ideal kesim değeri IgE için 2500 IU/l veya eozinofil için 1500/mm3 belirlendiğinde atopi ile HİES'i ayırmak mümkündür. Bu değerlerin altında atopik hastalıklar ön planda düşünülebilir. Ancak IgE 5000IU/l veya eozinofil 2500/mm3 olan hastalar aksi ispat edilene kadar HİES kabul edilmelidir.Objective: High serum IgE and eosinophil counts are laboratory features of severe atopic dermatitis (AD), persistent food allergies and severe allergic asthma as well as some primary immune deficiencies (PID), especially hyperIgE syndrome (HIES). Our objective was to define cut-off values to discriminate atopic diseases and HIES by comparing serum IgE, eosinophil levels, allergen sensitizations among patients with AD, IgE-mediated food allergy, allergic asthma and/or rhinitis, chronic granulomatous disease and HIES. Materials and Methods: A total of 315 patients were enrolled into the study. We evaluated serum IgE (IU/L) and eosinophil (/mm3) values, allergen sensitizations and the age range of patients. ROC curve analysis was performed in order to define an optimal cut-off value for serum IgE levels and blood eosinophil counts. Results: The median levels of serum IgE and eosinophils were 2542 (min:1, max:55400) and 1000 (min:0, max:37880), respectively in the PID group. In the atopy group, the median serum IgE was 265 (min:4, max:7122), and median eosinophil count was 400 (min:0, max:6050). Serum IgE and blood eosinophil levels were significantly higher in PID patients compared to those with atopic diseases (p>0.001 and p>0.001, respectively). IgE was statistically higher in the food allergy group compared to only house dust mite sensitized and/or grass co-sensitized patients (p0.008 and p0.01, respectively). If the IgE cut-off values for HIES are considered to be equal to 2000 GiRiş IgE2000 IU/l alındığında duyarlılık %74, &ouml;zg&uuml;nl&uuml;k %96 (PPD: %74, NPD: %96), IgE5000 IU/l için duyarlılık %56, &ouml;zg&uuml;nl&uuml;k %99 (PPD: %91, NPD: %94), eozinofil1500/mm3 alındığında duyarlılık %51, &ouml;zg&uuml;nl&uuml;k %96 (PPD: %61, NPD: %93), eozinofil2500/mm3 için duyarlılık %41, &ouml;zg&uuml;nl&uuml;k %98 (PPD: %76, NPD: %92) olarak belirlendi. Sonuç: ROC analizinde ideal kesim değeri IgE için 2500 IU/l veya eozinofil için 1500/mm3 belirlendiğinde atopi ile HİES'i ayırmak m&uuml;mk&uuml;nd&uuml;r. Bu değerlerin altında atopik hastalıklar &ouml;n planda d&uuml;ş&uuml;n&uuml;lebilir. Ancak IgE< 5000IU/l veya eozinofil< 2500/mm3 olan hastalar aksi ispat edilene kadar HİES kabul edilmelidir.IU/l, the sensitivity accounted for 74% and the specificity for 96% (PPV:74%, NPV:96%). When serum IgE5000 IU/l was considered as the cut-off, the sensitivity decreased to 56% in contrast to the specificity increasing to 99% (PPV:91%, NPV:94%). Similarly, for eosinophils1500/mm3, the sensitivity was %51 and the specificity 96% (PPV:61%, NPV:93%) and for eosinophils2500/mm3, the sensitivity was 41% while the specificity was 98% (PPV:76%, NPV: 92%) to discriminate HIES from atopic diseases.Conclusion: It is possible to discriminate atopic diseases from HIES when the cut-off values are used are 2500 IU/l for IgE and 1500/mm3 for eosinophils with ROC curve analysis. An atopic disease is the most likely underlying condition below these values. Moreover, patients with serum IgE higher than 5000 IU/l and/or blood eosinophils higher than 2500/mm3 should be managed as HIES unless otherwise proven

Diagnostic Usage of Intracellular Protein Staining by Flow Cytometer in Primary Immune Deficiencies; Marmara Experience

Objective: The aim of our study was the optimization and standardization of intracellular dedicator of cytokinesis 8 (DOCK8), LPS-responsive beige-like anchor protein (LRBA), SH2D1A/SLAM-ssociated protein (SAP) and X-linked inhibitor of apoptosis protein (XIAP) protein expressions in healthy controls with a single flow cytometer protocol and to concomitantly evaluate the possible use of this method for diagnosis

Comparison of oral microflora in selective IgA deficiency and X linked agammaglobulinemia cases with control group

Aim: X linked agammaglobulinemia (XLA) and selective IgA deficiency are predominantly antibody deficiency syndromes. Recurrent sinopulmonary infections are common problems observed in both diseases. IgG, IgM and salivary IgA which are present especially in gingival crevice are involved in the defense of the oral cavity. The aim of our study was to investigate oral mucosa, dental health and microfloral variation in selective IgA deficiency and XLA patients by comparison with the healthy group