Publications by authors named "Marissa Penna-Martinez"

Background: The one-step membrane technique, using a human acellular dermal matrix (hADM), is an experimental method for treating large bone defects. This eliminates the need for the Masquelet membrane induction step, shortening the procedure while maintaining effectiveness. However, previous studies showed that colonizing hADM with bone marrow mononuclear cells (BMC) worsens healing, likely due to the presence of CD8+ lymphocytes, which negatively affect bone regeneration.

View Article and Find Full Text PDF

Objective: While vitamin D regulates immune cells, little is known about it in autoimmune Addison's disease (AAD). We investigated the vitamin D status in AAD patients from five European populations to assess its deficiency. In addition, we studied two case-control cohorts for vitamin D metabolism and pathway genes.

View Article and Find Full Text PDF

Context: Autoimmune polyglandular syndrome (APS-2: autoimmune Addison's disease or type 1 diabetes) is conferred by predisposing HLA molecules, vitamin D deficiency, and heritable susceptibility. Organ destruction is accompanied by cytokine alterations. We addressed the monocytic cytokines of two distinct APS-2 cohorts, effects of vitamin D and HLA DQ risk.

View Article and Find Full Text PDF

Variants of vitamin D metabolism-genes may predispose to type 2 diabetes (T2D). This study investigated the impact of these variants on disease susceptibility, Vitamin D, parathyroid hormone, C-peptide and HbA1c levels before and after cholecalciferol supplementation in patients with T2D.Twelve polymorphisms within CYP2R1, CYP27B1, DBP, VDR and CYP24A1 were genotyped in 553 T2D patients and 916 controls.

View Article and Find Full Text PDF

Context: Autoimmune endocrinopathies result from environmental triggers on the genetic background of risk alleles, especially HLA-DR and HLA-DQ with alanine (Ala) in HLA-DQB1 position 57 (Ala57), whereas amino acid Asp57 is protective.

Objectives: Differentiate the effects of HLA-DQB1 amino acid variants at position 57 in adult patients with isolated endocrinopathies and autoimmune polyglandular syndrome type 2 (APS-2) compared with healthy controls in relation to gender.

Setting: University Hospital Frankfurt, Frankfurt, Germany.

View Article and Find Full Text PDF

The arachidonate 5-lipoxygenase (ALOX5) pathway has been implicated in chronic inflammatory disease which may be influenced by vitamin D due to vitamin D response elements (VDRE). We investigated an ALOX5 polymorphism (rs4987105) in patients with type 2 diabetes (T2D) and the in vitro effects of calcitriol (1,25(OH)D) on ALOX5 metabolism in monocytes of T2D patients and healthy controls (HC). 533 T2D and 473 HC were genotyped for the rs4987105 polymorphism.

View Article and Find Full Text PDF

Elevated sphingosine 1-phopshate (S1P) concentration was observed in type 2 diabetes mellitus (T2D). On the other side, 1α,25-dihydroxyvitamin D (1,25(OH)D) can influence the formation of sphingosine 1-phopshate (S1P) and the expression of S1P receptors, which are known to be involved in T2D. In order to evaluate mechanisms for the antiinflammatory potential of 1,25(OH)D, we investigated whether 1,25(OH)D alters S1P signaling and metabolism in human CD14 monocytes.

View Article and Find Full Text PDF

Protective effects of vitamin D have been reported in autoimmune and malignant thyroid diseases, though little is known about the underlying mechanism. Sirtuin 1 histon deacethylase (SIRT1) links the vitamin D pathway with regulation of transcription factor FOXO3a, a key player in cell cycle regulation and apoptosis. Aim of the present study was to investigate common single nucleotide polymorphisms (SNP's) in gene in respect to thyroid diseases, as well as to evaluate the hypothesis of Sirtuin1-FOXO3a interaction being a mediator of anti-proliferative vitamin D effects.

View Article and Find Full Text PDF

Objectives: On the basis of the immunomodulatory actions of vitamin D (VD), we investigated the effects of high-dose VD therapy over a 3 mo period on the immune response in patients with Addison's disease (AD).

Methods: This randomized, controlled, crossover trial included 13 patients with AD who received either cholecalciferol (4000 IU/d) for 3 mo followed by 3 mo placebo oil or the sequential alternative placebo followed by verum. Glucocorticoid replacement doses remained stable.

View Article and Find Full Text PDF

Sphingolipids are characterized by a broad range of bioactive properties. Particularly, the development of insulin resistance, a major pathophysiological hallmark of Type 2 Diabetes mellitus (T2D), has been linked to ceramide signaling. Since vitamin D supplementation may slow down T2D progression by improving glucose concentrations and insulin sensitivity, we investigated whether vitamin D supplementation impacts on plasma sphingolipid levels in T2D patients.

View Article and Find Full Text PDF

The etiology and pathophysiology of type 1 diabetes remain largely elusive with no established concepts for a causal therapy. Efforts to clarify genetic susceptibility and screening for environmental factors have identified the vitamin D system as a contributory pathway that is potentially correctable. This review aims at compiling all genetic studies addressing the vitamin D system in type 1 diabetes.

View Article and Find Full Text PDF

Background: Preventive measures and a causal therapy for type 1 diabetes (T1D) remain elusive. An imbalance between different dendritic cells (DC) with increased immunogenic DC and decreased tolerogenic DC (tDC) may lead to T1D. Furthermore, 25(OH)D3 is associated with less adverse effects than 1,25(OH)2D3.

View Article and Find Full Text PDF

The mechanisms behind destruction of the adrenal glands in autoimmune Addison's disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the disease. In this article, we demonstrate highly frequent 21-hydroxylase-specific T cells detectable in 20 patients with Addison's disease.

View Article and Find Full Text PDF

Background: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for.

Aim: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts.

View Article and Find Full Text PDF

Background: Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed.

View Article and Find Full Text PDF

Background: Single nucleotide polymorphisms (SNPs) near thyroid transcription factor genes (FOXE1 rs965513/NKX2-1 rs944289) have been shown to be associated with differentiated thyroid cancer (DTC) in Caucasoid populations. We investigated the role of those SNPs in German patients with DTC and also extended our analysis to tumor stages and lymphocytic infiltration of the tumors (ITL).

Methods: Patients with DTC (n=243; papillary, PTC; follicular, FTC) and healthy controls (HC; n=270) were analyzed for the rs965513 and rs944289 SNPs.

View Article and Find Full Text PDF

Vitamin D is a secosteroid hormone that resembles other nuclear steroid hormones such as thyroid, gluco-, and mineralocorticoids, as well as gonadal effector systems. Primarily understood as a master regulator of bone and calcium/phosphate physiology, it is now increasingly recognized as orchestrating numerous aspects of cell growth and differentiation in many tissues, including those of innate and acquired immunity. This review addresses recently discovered aspects that highlight vitamin D's potential for immune intervention and how the vitamin D pathway is utilized for anti-infective and antineoplastic immunity.

View Article and Find Full Text PDF

Background: Common polymorphisms of the vitamin D receptor gene have been reported to affect the risk of breast, colon, prostate, and differentiated thyroid cancer (DTC), but polymorphisms within the genes of vitamin D metabolizing enzymes have not been studied in DTC. The aim of the present study was to investigate the genes for vitamin D enzymes in patients with DTC and healthy controls (HC) as well as the vitamin D (25-hydroxyvitamin D(3), and 1,25-hydroxyvitamin) status.

Methods: German patients (n=253) with DTC (papillary thyroid carcinoma [PTC] and follicular thyroid carcinoma [FTC]) and HC (n=302) were genotyped for polymorphisms within the vitamin D metabolizing enzymes such as 25-hydroxylase (CYP2R1[rs12794714, rs10741657]), 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1[rs10877012, rs4646536]), and 25-hydroxyvitamin D 24-hydrolase (CYP24A1[rs927650, rs2248137, rs2296241]).

View Article and Find Full Text PDF

Background: Megalin and cubilin bind and internalize the 25(OH)D3-DBP complex in the kidney. Once the complex is internalized, 25(OH)D3 is released and activated to 1,25(OH)2D3 the ligand for the vitamin D receptor (VDR). Supporting the important role of cubilin in this process recent findings showed that cubilin deficiency results in decrease of 25(OH)D3 and 1,25(OH)2D3 plasma levels.

View Article and Find Full Text PDF

Background: Three genes have been confirmed as major joint susceptibility genes for endocrine autoimmune disease:human leukocyte antigen class II, cytotoxic T-lymphocyte antigen 4 and protein tyrosine phosphatase non-receptor type 22. Recent studies showed that a genetic variation within the interferon induced helicase domain 1 (IFIH1) locus (rs1990760 polymorphism) is an additional risk factor in type 1 diabetes and Graves' disease (GD).

Methods: The aim of the present study was to investigate the role of the rs1990760 polymorphism within the IFIH1 gene in German patients with GD (n = 258), Hashimoto's thyroiditis (HT, n = 106), Addison's disease (AD, n = 195) and healthy controls (HC, n = 227) as well as in 55 GD families (165 individuals, German) and 100 HT families (300 individuals, Italian).

View Article and Find Full Text PDF

Background: Vitamin D receptor (VDR) expression has been shown to be upregulated in several tumors and is supposed to represent an important endogenous response to tumor progression. To investigate the role of the VDR gene and its influence on 25(OH)D(3) and 1,25(OH)(2)D(3) plasma levels in thyroid carcinoma, we analyzed four VDR polymorphisms in patients and healthy controls (HC).

Methods: Patients with thyroid carcinoma (n = 172) (n = 132 for papillary and n = 40 for follicular) and HC (n = 321) were genotyped for the ApaI (rs7975232), TaqI (rs731236), BsmI (rs1544410), and FokI (rs10735810) polymorphisms within the VDR gene and correlated with 25(OH)D(3) and 1,25(OH)(2)D(3) plasma levels.

View Article and Find Full Text PDF

Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease. Although the precise mechanisms leading to the destruction of islet beta cells are unknown, diverse studies support a role of the CXCR3-binding chemokines. A combination of a case (n = 447)-control (n = 300) and family (n = 221) analysis was performed to investigate the role of the CXCL9 (rs10336, rs3733236) and CXCL10 (rs3921, rs35795399 and rs8878) polymorphisms and their interaction with HLA high-risk haplotypes DQ2(DQA*0501-DQB*0201)-DQ8(DQA*0301-DQB*0302) in T1D.

View Article and Find Full Text PDF

Background: Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from beta-cell autoimmunity.

Methods: We investigated the role of the -2221Msp(C/T) and -23HphI(A/T) polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317), Addison's disease (AD, n = 107) or Hashimoto's thyroiditis (HT, n = 61)], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62) as well as in healthy controls (HC, n = 275).

Results: T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T) and "AA" -23HphI(A/T) polymorphisms than the HC (78.

View Article and Find Full Text PDF