Search Results (7)

Feto-maternal microchimerism is the bidirectional transfer of cells through the placenta during pregnancy that can affect the health of both the mother and the offspring, even in childhood or adulthood. However, microchimerism seems to have different consequences in the mother, who already has a developed immune system, than in the fetus, which is vulnerable with immature defense mechanisms. Studies have shown that the presence of fetal microchimeric cells in the mother can be associated with reduced fetal growth, pre-eclampsia, miscarriage, premature birth, and the risk of autoimmune disease development in the future. However, some studies report that they may also play a positive role in the healing of maternal tissue, in cancer and cardiovascular disease. There are few studies in the literature regarding the role of maternal microchimeric cells in fetal autoimmunity. Even fewer have examined their association with the potential triggering of autoimmune diseases later in the offspring’s life. The objectives of this review were to elucidate the mechanisms underlying the potential association between maternal cells and autoimmune conditions in offspring. Based on our findings, several hypotheses have been proposed regarding possible mechanisms by which maternal cells may trigger autoimmunity. In Type 1 diabetes, maternal cells have been implicated in either attacking the offspring’s pancreatic β-cells, producing insulin, differentiating into endocrine and exocrine cells, or serving as markers of tissue damage. Additionally, several potential mechanisms have been suggested for the onset of neonatal lupus erythematosus. In this context, maternal cells may induce a graft-versus-host or host-versus-graft reaction in the offspring, function as effectors within tissues, or contribute to tissue healing. These cells have also been found to participate in inflammation and fibrosis processes, as well as differentiate into myocardial cells, potentially triggering an immune response. Moreover, the involvement of maternal microchimeric cells has been supported in conditions such as juvenile idiopathic inflammatory myopathies, Sjögren’s syndrome, systemic sclerosis, biliary atresia, and rheumatoid arthritis. Conversely, no association has been found between maternal cells and celiac disease in offspring. These findings suggest that the role of maternal cells in autoimmunity remains a controversial topic that warrants further investigation. Full article

Background and Objectives: Wolfram syndrome type 1 (OMIM# 222300; ORPHAcode 3463) is an extremely rare autosomal recessive syndrome with a 25% recurrence risk in children. It is characterized by the presence of juvenile-onset diabetes mellitus (DM), progressive optic atrophy (OA), diabetes insipidus (DI), and sensorineural deafness (D), often referred to by the acronym DIDMOAD. It is a severe neurodegenerative disease with a life expectancy of 39 years, with death occurring due to cerebral atrophy. For a positive diagnosis, the presence of diabetes mellitus and optic nerve atrophy is sufficient. The disease occurs because of pathogenic variants in the WFS1 gene. The aim of this article is to present a case report of Wolfram Syndrome Type I, alongside a review of genetic variants, clinical manifestations, diagnosis, therapy, and long-term management. Emphasizing the importance of early diagnosis and a multidisciplinary approach, the study aims to enhance understanding and improve outcomes for patients with this complex syndrome. Materials and Methods: A case of a 28-year-old patient diagnosed with DM at the age of 6 and with progressive optic atrophy at 26 years old is presented. Molecular diagnosis revealed the presence of a heterozygous nonsense variant WFS1 c.1943G>A (p.Trp648*), and a heterozygous missense variant WFS1 c.1675G>C (p.Ala559Pro). Results: The molecular diagnosis of the patient confirmed the presence of a heterozygous nonsense variant and a heterozygous missense variant in the WFS1 gene, correlating with the clinical presentation of Wolfram syndrome type 1. Both allelic variants found in our patient have been previously described in other patients, whilst this combination has not been described before. Conclusions: This case report and review underscores the critical role of early recognition and diagnosis in Wolfram syndrome, facilitated by genetic testing. By identifying pathogenic variants in the WFS1 gene, genetic testing not only confirms diagnosis but also guides clinical management and informs genetic counseling for affected families. Timely intervention based on genetic insights can potentially reduce the progressive multisystem manifestations of the syndrome, thereby improving the quality of life and outcomes for patients. Full article

As the prevalence of juvenile-onset obesity rises globally, the multitude of related health consequences gain significant importance. In this context, obesity is associated with impaired cutaneous wound healing. In experimental settings, mice are the most frequently used model for investigating the effect of high-fat diet (HFD) chow on wound healing in wild-type or genetically manipulated animals, e.g., diabetic ob/ob and db/db mice. However, these studies have mainly been performed on adult animals. Thus, in the present study, we introduced a mouse model for a juvenile onset of obesity. We exposed 4-week-old mice to an investigational feeding period of 9 weeks with an HFD compared to a regular diet (RD). At a mouse age of 13 weeks, we performed excisional and incisional wounding and measured the healing rate. Wound healing was examined by serial photographs with daily wound size measurements of the excisional wounds. Histology from incisional wounds was performed to quantify granulation tissue (thickness, quality) and angiogenesis (number of blood vessels per mm²). The expression of extracellular matrix proteins (collagen types I/III/IV, fibronectin 1, elastin), inflammatory cytokines (MIF, MIF-2, IL-6, TNF-α), myofibroblast differentiation (α-SMA) and macrophage polarization (CD11c, CD301b) in the incisional wounds were evaluated by RT-qPCR and by immunohistochemistry. There was a marked delay of wound closure in the HFD group with a decrease in granulation tissue quality and thickness. Additionally, inflammatory cytokines (MIF, IL-6, TNF-α) were significantly up-regulated in HFD- when compared to RD-fed mice measured at day 3. By contrast, MIF-2 and blood vessel expression were significantly reduced in the HFD animals, starting at day 1. No significant changes were observed in macrophage polarization, collagen expression, and levels of TGF-β1 and PDGF-A. Our findings support that an early exposition to HFD resulted in juvenile obesity in mice with impaired wound repair mechanisms, which may be used as a murine model for obesity-related studies in the future. Full article

Type-1 diabetes, an autoimmune disease characterized by damage to pancreatic insulin-producing beta cells, is associated with adverse renal, retinal, cardiovascular, and cognitive outcomes, possibly including dementia. Moreover, the protozoal parasite Toxoplasma gondii has been associated with type-1 diabetes. To better characterize the association between type-1 diabetes and Toxoplasma gondii infection, we conducted a systematic review and meta-analysis of published studies that evaluated the relationship between type-1 diabetes and Toxoplasma gondii infection. A random-effects model based on nine primary studies (total number of participants = 2655) that met our inclusion criteria demonstrated a pooled odds ratio of 2.45 (95% confidence interval, 0.91–6.61). Removing one outlying study increased the pooled odds ratio to 3.38 (95% confidence interval, 2.09–5.48). These findings suggest that Toxoplasma gondii infection might be positively associated with type-1 diabetes, although more research is needed to better characterize this association. Additional research is required to determine whether changes in immune function due to type-1 diabetes increase the risk of infection with Toxoplasma gondii, infection with Toxoplasma gondii increases the risk of type-1 diabetes, or both processes occur. Full article

Youth-onset Type 2 Diabetes Mellitus (T2DM) represents a major burden worldwide. In the last decades, the prevalence of T2DM became higher than that of Type 1 Diabetes Mellitus (T1DM), helped by the increasing rate of childhood obesity. The highest prevalence rates of youth-onset T2DM are recorded in China (520 cases/100,000) and in the United States (212 cases/100,000), and the numbers are still increasing. T2DM young people present a strong hereditary component, often unmasked by social and environmental risk factors. These patients are affected by multiple coexisting risk factors, including obesity, hyperglycemia, dyslipidemia, insulin resistance, hypertension, and inflammation. Juvenile T2DM nephropathy occurs earlier in life compared to T1DM-related nephropathy in children or T2DM-related nephropathy in adult. Diabetic kidney disease (DKD) is T2DM major long term microvascular complication. This review summarizes the main mechanisms involved in the pathogenesis of the DKD in young population and the recent evolution of treatment, in order to reduce the risk of DKD progression. Full article

Juvenile hemochromatosis (JH), type 2A hemochromatosis, is a rare autosomal recessive disorder of systemic iron overload due to homozygous mutations of HJV (HFE2), which encodes hemojuvelin, an essential regulator of the hepcidin expression, causing liver fibrosis, diabetes, and heart failure before 30 years of age, often with fatal outcomes. We report two Japanese sisters of 37 and 52 years of age, with JH, who showed the same homozygous HJV I281T mutation and hepcidin deficiency and who both responded well to phlebotomy on an outpatient basis. When all reported cases of JH with homozygous HJV mutations in the relevant literature were reviewed, we found—for the first time—that JH developed in females and males at a ratio of 3:2, with no age difference in the two groups. Furthermore, we found that the age of onset of JH may depend on the types of HJV mutations. In comparison to patients with the most common G320V/G320V mutation, JH developed earlier in patients with L101P/L101P or R385X/R385X mutations and later in patients with I281T/I281T mutations. Full article

Endocannabinoid system consists of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors, their endogenous ligands, and the enzymes responsible for their synthesis and degradation. CB2, to a great extent, and CB1, to a lesser extent, are involved in regulating the immune response. They also regulate the inflammatory processes by inhibiting pro-inflammatory mediator release and immune cell proliferation. This review provides an overview on the role of the endocannabinoid system with a major focus on cannabinoid receptors in the pathogenesis and onset of inflammatory and autoimmune pediatric diseases, such as immune thrombocytopenia, juvenile idiopathic arthritis, inflammatory bowel disease, celiac disease, obesity, neuroinflammatory diseases, and type 1 diabetes mellitus. These disorders have a high social impact and represent a burden for the healthcare system, hence the importance of individuating more innovative and effective treatments. The endocannabinoid system could address this need, representing a possible new diagnostic marker and therapeutic target. Full article