Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease

Purpose Hyper-IgE syndrome (HIES) is a severe primary immunodeficiency, characterized by increased serum IgE levels as well as recurrent infections and atopic dermatitis (AD)-like skin lesions. AD is a chronic inflammatory skin disease with immunologic alterations (Th2-Th22 polarization) and characteristic skin barrier dysfunctions. Our aim was to investigate physicochemical skin barrier alterations and allergic sensitization in STAT3-HIES patients in order to explore whether skin barrier dysfunction can play a role in the eczematoid skin lesions in these patients. Methods In our experiments STAT3 and FLG mutation analyses were performed in STAT3-HIES (n=7) and AD (n=49) patients. Laboratory parameters (LDH and Eos counts), immunologic alterations (Th17 cell counts), allergic sensitization (total and specific IgE levels, skin prick tests, and medical history records), skin barrier changes [transepidermal water loss (TEWL), skin pH], serum and stratum corneum thymic stromal lymphopoietin (TSLP) levels were also examined.Results Impaired Th17 cell numbers, but normal physicochemical barrier functions, as well as serum and stratum corneum TSLP levels, were found in STAT3-HIES, while these parameters were significantly altered in AD patients. Allergic sensitization was detected in nearly all AD patients, while no signs of sensitization occurred in STAT3-HIES. Conclusions Our study demonstrated that the skin barrier functions of STAT3-HIES patients are not damaged and they differ significantly from the altered skin barrier functions of AD patients. A well-functioning physicochemical skin barrier may be one of the explanations on the contradiction between the extremely high total IgE levels and the lack of allergic sensitization in these patients. Our study underlines the importance of skin barrier in the development of allergic sensitization.

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“…Measurement of IL-17 producing T cells was performed to strengthen the diagnosis of STAT3-HIES patients as described previously [15].…”

Section: Evaluation Of Intracellular Il-17 By Flow Cytometrymentioning

confidence: 99%

Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome

et al. 2015

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“…Deficiency in 25(OH)D may lead to hypocalcemia, hyperparathyroidism, and diminished bone mineral density/content. Vitamin D deficiency has also been associated with multiple systemic effects including elevated blood pressure [15, 16], metabolic syndrome, cardiovascular disease [17], anemia [18], and impaired immune system regulation [19]. …”

Section: Introductionmentioning

confidence: 99%

Vitamin D in incident nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study

et al. 2015

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Background Cross-sectional studies of children with prevalent nephrotic syndrome (NS) have shown 25-vitamin D (25(OH)D) deficiency rates of 20–100 %. Information on 25(OH)D status in incident patients or following remission is limited. This study aimed to assess 25(OH)D status of incident idiopathic NS children at presentation and longitudinally with short-term observation. Methods Multicenter longitudinal study of children (2–18 years old) from 14 centers across the Midwest Pediatric Nephrology Consortium with incident idiopathic NS. 25(OH)D levels were assessed at diagnosis and 3 months later. Results Sixty-one children, median age 5 (3, 11) years, completed baseline visit and 51 completed second visit labs. All 61 (100 %) had 25(OH)D<20 ng/ml at diagnosis. Twenty-seven (53 %) had 25(OH)D<20 ng/ml at follow-up. Fourteen (28 %) children were steroid resistant. Univariate analysis showed that children prescribed vitamin D supplements were less likely to have 25(OH)D deficiency at follow-up (OR 0.2, 95 % CI 0.04, 0.6). Steroid response, age, and season did not predict 25(OH)D deficiency. Multivariable linear regression modeling showed higher 25(OH)D levels at follow-up by 13.2 ng/ml (SE 4.6, p<0.01) in children supplemented with vitamin D. Conclusions In this incident idiopathic NS cohort, all children at diagnosis had 25(OH)D deficiency and the majority continued to have a deficiency at 2–4 months. Supplemental vitamin D decreased the odds of 25(OH)D deficiency at follow-up, supporting a role for supplementation in incident NS.

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“…(50) Importantly, Zold et al showed that the UCTD patients with the lowest vitamin D levels were the ones who tended to transition to a defined connective tissue disease (50) and that low vitamin D levels in UCTD patients impaired regulatory T-cell homeostasis. (51) …”

Section: Introductionmentioning

confidence: 99%

Preclinical Systemic Lupus Erythematosus

Robertson¹,

James²

2014

Rheumatic Disease Clinics of North America

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Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease

Abstract: Our findings support the idea that vitamin D influences the Th17/nTreg imbalance in vitamin D-insufficient patients with UCTD and could be beneficial in the management of the disease.

Cited by 32 publications

References 58 publications

Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome

Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome

Vitamin D in incident nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study

Preclinical Systemic Lupus Erythematosus

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