Altered molecular repertoire of immune system by renal dysfunction in the elderly: is prediction and targeted prevention in the horizon?

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Abstract

Background

Patients on chronic hemodialysis (HD) have impaired cellular and humoral immunity. The percentage of elderly people among the total population in Taiwan is increasing dramatically, and HD is the primary alternative for renal replacement therapy when renal function declines. Activated vitamin D is widely used in HD patients with secondary hyperparathyroidism (SHPT) and is a well-known immunomodulatory agent. Personalized medicine and integrative medical approach has been a trend in current clinical practice. Can we improve their immune function using vitamin D in spite of the mineral aspect? Here, we investigated the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and T cell differentiation in chronic HD patients.

Methods

Forty patients with chronic HD were enrolled. HD patients with SHPT had been treated with activated vitamin D for 3 months. Peripheral blood mononuclear cells obtained from the patients were cultured and stimulated by mitogens, and T cells were analyzed by flow cytometry. Serum 25(OH)D levels were detected by enzyme-linked immunosorbent assay.

Results

The incidence of T cell differentiation to the T helper cell (Th)2 subtype was more prevalent in the elderly group than in the controls ( p = 0.001). Th2 differentiation was also correlated with age ( p = 0.004) and serum 25(OH)D levels ( p < 0.05). After treated with activated vitamin D, the level of Th1 cytokines decreased while the Th2 cytokine level increased in the sera ( p < 0.05). The T cell differentiation tended toward the Th2 subtype ( p = 0.027) after treatment of activated vitamin D in SHPT patients.

Conclusions

These results demonstrated that Th2 differentiation is correlated with age and the serum 25(OH)D level of patients. Treatment with activated vitamin D influenced T cell differentiation and cytokine expression in SHPT patients. Taking vitamin D is the possible prediction and targeted treatment in the immune dysfunction in chronic HD patients.

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Most cited references 34

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Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation.

Sheng Chen, Gary P. Sims, Xiao Chen … (2007)

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) can modulate immune responses, but whether it directly affects B cell function is unknown. Patients with systemic lupus erythematosus, especially those with antinuclear Abs and increased disease activity, had decreased 1,25(OH)(2)D(3) levels, suggesting that vitamin D might play a role in regulating autoantibody production. To address this, we examined the effects of 1,25(OH)(2)D(3) on B cell responses and found that it inhibited the ongoing proliferation of activated B cells and induced their apoptosis, whereas initial cell division was unimpeded. The generation of plasma cells and postswitch memory B cells was significantly inhibited by 1,25(OH)(2)D(3), although the up-regulation of genetic programs involved in B cell differentiation was only modestly affected. B cells expressed mRNAs for proteins involved in vitamin D activity, including 1 alpha-hydroxylase, 24-hydroxylase, and the vitamin D receptor, each of which was regulated by 1,25(OH)(2)D(3) and/or activation. Importantly, 1,25(OH)(2)D(3) up-regulated the expression of p27, but not of p18 and p21, which may be important in regulating the proliferation of activated B cells and their subsequent differentiation. These results indicate that 1,25(OH)(2)D(3) may play an important role in the maintenance of B cell homeostasis and that the correction of vitamin D deficiency may be useful in the treatment of B cell-mediated autoimmune disorders.

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Vitamin D levels and early mortality among incident hemodialysis patients.

M. Wolf, A. Shah, O. Gutiérrez … (2007)

Vitamin D deficiency is associated with cardiovascular disease, the most common cause of mortality in hemodialysis patients. To investigate the relation between blood levels of 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) with hemodialysis outcomes, we measured baseline vitamin D levels in a cross-sectional analysis of 825 consecutive patients from within a prospective cohort of incident US hemodialysis patients. Of these patients, 78% were considered vitamin D deficient with 18% considered severely deficient. Calcium, phosphorus, and parathyroid hormone levels correlated poorly with 25D and 1,25D concentrations. To test the association between baseline vitamin D levels and 90-day mortality, we selected the next 175 consecutive participants who died within 90 days and compared them to the 750 patients who survived in a nested case-control analysis. While low vitamin D levels were associated with increased mortality, significant interaction was noted between vitamin D levels, subsequent active vitamin D therapy, and survival. Compared to patients with the highest 25D or 1,25D levels who received therapy, untreated deficient patients were at significantly increased risk for early mortality. Our study shows that among incident hemodialysis patients, vitamin D deficiency is common, correlates poorly with other components of mineral metabolism and is associated with increased early mortality.

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Vitamin D and inflammation.

Luca Semerano, Geraldine Falgarone, Nathalie Saidenberg-Kermanac’h … (2010)

Calcitriol, or 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D3) is a well-known endocrine regulator of calcium homeostasis. More recently, local calcitriol production by immune cells was shown to exert autocrine or paracrine immunomodulating effects. Immune cells that produce calcitriol also express the vitamin D receptor (VDR) and the enzymes needed to metabolize vitamin D3 (1α-, 25-, and 24-hydroxylases). Studies of animal models and cell cultures showed both direct and indirect immunomodulating effects involving the T cells, B cells, and antigen-presenting cells (dendritic cells and macrophages) and affecting both innate and adaptive immune responses. The overall effect is a switch from the Th1/Th17 response to the Th2/Treg profile. The immunomodulating effects of vitamin D may explain the reported epidemiological associations between vitamin D status and a large number of autoimmune and inflammatory diseases. Such associations have been suggested by observational studies not only in rheumatoid arthritis, lupus, inflammatory bowel disease, and type 1 diabetes; but also in infections, malignancies, transplant rejection, and cardiovascular disease. In animal models for these diseases, vitamin D supplementation has been found to produce therapeutic effects. Thus, vitamin D is a key focus for public health efforts and may hold promise for the treatment of dysimmune diseases. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

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Author and article information

Contributors

Cheng-Lin Lang

Min-Hui Wang

Kuan-Yu Hung

Chih-Kang Chiang

Kuo-Cheng Lu

Journal

Journal ID (nlm-ta): EPMA J

Journal ID (iso-abbrev): EPMA J

Title: The EPMA Journal

Publisher: BioMed Central

ISSN (Print): 1878-5077

ISSN (Electronic): 1878-5085

Publication date Collection: 2013

Publication date (Electronic): 21 June 2013

Volume: 4

Issue: 1

Page: 17

Affiliations

[1 ]Division of Nephrology, Department of Internal Medicine, Cardinal Tien Hospital, Yong-He Branch, Taipei 234, Taiwan

[2 ]Division of Nephrology, Department of Internal Medicine, Cardinal Tien Hospital & School of Medicine, Fu-Jen Catholic University, New Taipei City 231, Taiwan

[3 ]Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital & College of Medicine, National Taiwan University, Taipei 10048, Taiwan

Article

Publisher ID: 1878-5085-4-17

DOI: 10.1186/1878-5085-4-17

PMC ID: 3728042

PubMed ID: 23800151

SO-VID: f8263573-76b2-4462-ad4b-b16b56f158c3

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Altered molecular repertoire of immune system by renal dysfunction in the elderly: is prediction and targeted prevention in the horizon?

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Abstract

Background

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Conclusions

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Neuronal Signaling

Most cited references 34

Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation.

Vitamin D levels and early mortality among incident hemodialysis patients.

Vitamin D and inflammation.

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