Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE-dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell ...(MC) disorders, and hereditary alpha tryptasemia (HAT). MCA-related symptoms range from mild to severe to life-threatening. The severity of MCA-related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual's baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC-stabilizing or mediator-targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where
-mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE-dependent allergy or other reactive MCA-triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor
-mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where
-mutated MCs, IgE-dependent allergies and sometimes HAT are detected. These patients may suffer from life-threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE-blocking antibodies, anti-mediator-type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co-morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine.
Mastocytosis is a rare and complex disease characterized by expansion of clonal mast cells (MC) in skin and/or various internal organ systems. Involvement of internal organs leads to the diagnosis of ...systemic mastocytosis (SM). The WHO classification divides SM into indolent SM, smoldering SM and advanced SM variants, including SM with an associated hematologic neoplasm, aggressive SM, and MC leukemia. Historically, genetic analysis of individuals with pure cutaneous mastocytosis (CM) and SM have focused primarily on cohort studies of inherited single nucleotide variants and acquired pathogenic variants. The most prevalent pathogenic variant (mutation) in patients with SM is
p.D816V, which is detectable in most adult patients. Other somatic mutations have also been identified-especially in advanced SM-in
,
,
,
,
and
, and shown to impact clinical and cellular phenotypes. Although only small patient cohorts have been analyzed, disease associations have also been identified in several germline variants within genes encoding certain cytokines or their receptors (
,
,
,
,
) and toll-like receptors. More recently, an increased prevalence of hereditary alpha-tryptasemia (HαT) caused by increased
copy number encoding alpha-tryptase has been described in patients with SM. Whereas HαT is found in 3-6% of general Western populations, it is identified in up to 17% of patients with SM. In the current manuscript we review the prevalence, functional role and clinical impact of various germline and somatic genetic variants in patients with mastocytosis.
Interleukin-31 (IL-31) impact on the development and clinical presentation of psoriasis as well as pruritus has not been widely investigated so far.
To analyse IL-31 -1066G/A and -2057G/A promoter ...gene polymorphisms as well as serum IL-31 level and their correlation with severity of psoriasis and pruritus in the population of northern Poland.
The study included 300 psoriasis patients and 186 healthy volunteers. The polymorphisms were analysed using amplified refractory mutation system - polymerase chain reaction (ARMS-PCR) method. Serum levels of IL-31 were measured using the enzyme-linked immunosorbent assay (ELISA) test.
The -1066 AA genotype of the IL-31 gene was statistically more frequent in patients and it increased the risk of psoriasis (OR = 1.80;
= 0.04). The GG genotype as well as G allele of the IL-31 -2057 gene polymorphism were rarely observed in psoriasis and were associated with a decreased risk of the disease (OR = 0.6,
= 0.007 and OR = 0.7,
= 0.01, respectively). Serum levels of IL-31 were significantly elevated in psoriasis patients (
< 0.000001), however, they did not correlate with the studied polymorphic variants of the IL-31 gene, severity of psoriasis, disease onset, presence of psoriatic arthritis and pruritus intensity.
Distinct IL-31 promoter gene polymorphisms may be involved in psoriasis development. It seems that serum concentration of IL-31 may not be a reliable marker of psoriatic pruritus.
Ultraviolet radiation B stimulates both the production of vitamin D3 in the skin and the activation of the skin analog of the hypothalamic-pituitary-adrenal axis (HPA) as well as the central HPA. ...Since the role of vitamin D3 in the regulation of the HPA is largely unknown, we investigated the impact of 1,25(OH)2D3 and its noncalcemic analogs, 20(OH)D3 and 21(OH)pD, on the expression of the local HPA in human epidermal keratinocytes. The noncalcemic analogs showed similar efficacy to 1,25(OH)2D3 in stimulating the expression of neuropeptides, CRF, urocortins and POMC, and their receptors, CRFR1, CRFR2, MC1R, MC2R, MC3R and MC4R. Interestingly, unlike other secosteroids, the activity of 21(OH)pD did not correlate with induction of differentiation, suggesting a separate but overlapping mechanism of action. Thus, biologically active forms of vitamin D can regulate different elements of the local equivalent of the HPA with implications for the systemic HPA.
•Vitamin D3 stimulates skin analog of hypothalamus-pituitary-adrenal axis (sHPA).•Noncalcemic analogs – 20(OH)D3 and 21(OH)pD – show similar potency to 1,25(OH)2D3 in regulation of sHPA.•Activity of 21(OH)pD do not correlate with induction of differentiation, suggesting a separate mechanism of action.•Vitamin D3 may form addition link between cellular response to ultraviolet radiation and activation of sHPA axis.
Interleukin 16 (IL-16) has been described as a significant cytokine involved in the recruitment of CD4+ cells during inflammation; however, its potential role in psoriasis has not been defined. Our ...aim was to investigate the IL-16 serum levels and IL-16 mRNA skin expression in psoriasis patients in correlation with disease severity and mRNA skin expression for CD4. Moreover, the IL-16 skin localization was assessed and the -295 T/C IL-16 polymorphism was analyzed. For this exploratory, observational, and cross-sectional study, 97 unrelated patients with chronic plaque type psoriasis and 104 healthy controls were enrolled. IL-16 serum levels were significantly increased in patients compared with controls (P = 0.000022) and positively correlated with Psoriasis Area and Severity Index (r = 0.34, P = 0.0007), Body Surface Area (r = 0.34, P = 0.01) and were significantly higher in individuals with moderate to severe psoriasis (P = 0.0029). There was no significant correlation between IL-16 serum levels and Dermatology Quality of Life Index and no differences in genotype and allele frequencies for -295 T/C IL-16 polymorphism. The expression of IL-16 (mRNA and protein) was elevated in the margin of psoriatic skin while statistically significant increase in IL-16 immunoreactivity, but not in mRNA level, was observed within plaques. Furthermore, the IL-16 mRNA levels within psoriatic lesions positively correlated with the levels of CD4 mRNA, but not with Psoriasis Area and Severity Index. In conclusion, our data revealed an association between circulating IL-16 and severity of psoriasis which indicates that this cytokine could serve as a potential marker of disease activity. However, further investigations are required.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Circadian genes are a set of genes that regulate the body's internal clock and influence various physiological processes, including sleep-wake cycles, metabolism and immune function. Skin cutaneous ...melanoma (SKCM) is a type of skin cancer that arises from the pigment-producing cells in the skin and is the most deadly form of skin cancer. This study has investigated the relevance of circadian gene expression and immune infiltrations in the outcomes of cutaneous melanoma patients. In the present study, in silico methods based on the GEPIa, TIMER 2.0 and cBioPortal databases were performed, so as to investigate the transcript level and prognostic value of 24 circadian genes in SKCM and their relationship with the immune infiltration level. The in silico analysis showed that significantly more than half of the investigated circadian genes have an altered transcript pattern in cutaneous melanoma compared to normal skin. The mRNA levels of
and
were upregulated, whereas those of
,
,
,
,
,
,
,
,
,
,
and
were downregulated. The presented research shows that SKCM patients with at least one alteration of their circadian genes have decreased overall survival. Additionally, majority of the circadian genes are significantly corelated with the immune cells' infiltration level. The strongest correlation was found for neutrophils and was followed by circadian genes:
r = 0.52
< 0.0001,
r = 0.509
< 0.0001;
r = 0.45
< 0.0001;
r = 0.45
< 0.0001;
r = 0.44
< 0.0001. The infiltration level of immune cells in skin tumors has been associated with patient prognosis and treatment response. Circadian regulation of immune cell infiltration may further contribute to these prognostic and predictive markers. Examining the correlation between circadian rhythm and immune cell infiltration can provide valuable insights into disease progression and guide personalized treatment decisions.
Gamma delta (γδ) T cells are a heterogeneous population of cells that play roles in inflammation, host tissue repair, clearance of viral and bacterial pathogens, regulation of immune processes, and ...tumor surveillance. Recent research suggests that these are the main skin cells that produce interleukin-17 (I-17). Furthermore, γδ T cells exhibit memory-cell-like characteristics that mediate repeated episodes of psoriatic inflammation. γδ T cells are found in epithelial tissues, where many cancers develop. There, they participate in antitumor immunity as cytotoxic cells or as immune coordinators. γδ T cells also participate in host defense, immune surveillance, and immune homeostasis. The aim of this review is to present the importance of γδ T cells in physiological and pathological diseases, such as psoriasis, atopic dermatitis, autoimmune diseases, cancer, and lymphoma.
Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when ...a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier's sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.
Mastocytosis is a heterogeneous group of hematologic neoplasms defined by an accumulation of neoplastic mast cells (MC) in the skin, bone marrow, and other visceral organs ...
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