Melatonin in Dermatologic Allergic Diseases and Other Skin Conditions: Current Trends and Reports.

Melatonin is the main hormone that regulates the sleep cycle, and it is mostly produced by the pineal gland from the amino acid tryptophan. It has cytoprotective, immunomodulatory, and anti-apoptotic effects. Melatonin is also one of the most powerful natural antioxidants, directly acting on free radicals and the intracellular antioxidant enzyme system. Furthermore, it participates in antitumor activity, hypopigmentation processes in hyperpigmentary disorders, anti-inflammatory, and immunomodulating activity in inflammatory dermatoses, maintaining the integrity of the epidermal barrier and thermoregulation of the body. Due predominantly to its positive influence on sleep, melatonin can be used in the treatment of sleep disturbances for those with chronic allergic diseases accompanied by intensive itching (such as atopic dermatitis and chronic spontaneous urticaria). According to the literature data, there are also many proven uses for melatonin in photoprotection and skin aging (due to melatonin's antioxidant effects and role in preventing damage due to DNA repair mechanisms), hyperpigmentary disorders (e.g., melasma) and scalp diseases (such as androgenic alopecia and telogen effluvium).

Incidence of immediate allergic reactions to mRNA COVID-19 vaccines in adults with drug allergies and other allergic disorders.

Concerns have been raised about allergic reactions to messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccines. A history of allergic reactions, including anaphylaxis to drugs, has been frequently reported in individuals with anaphylaxis to mRNA vaccines. To estimate the rate of immediate allergic reactions in patients with a history of drug allergy or other allergic disorders. We included adult patients who had received at least 1 dose of an mRNA COVID-19 vaccine at the Special Hospital for Pulmonary Diseases between March 1, 2021, and October 1, 2021, and who reported a history of drug allergy or other allergic diseases (asthma, allergic rhinitis, atopic dermatitis, food or insect venom allergy, mastocytosis, idiopathic anaphylaxis, acute or chronic urticaria, and/or angioedema). Immediate allergic reactions, including anaphylaxis, occurring within 4 hours of vaccination were recorded. Six immediate allergic reactions were noted in the cohort of 1679 patients (0.36%). One patient experienced anaphylaxis (0.06%), which resolved after epinephrine administration, and the other reactions were mild and easily treatable. Most patients with a history of allergies can safely receive an mRNA COVID-19 vaccine, providing adequate observation periods and preparedness to recognize and treat anaphylaxis.

FasL (rs763110) gene polymorphism is not associated with susceptibility to rheumatoid arthritis in Croatian population.

AIM: To investigate the association of FasL gene polymorphism (rs763110) with rheumatoid arthritis occurrence, disease activity, and tumor necrosis factor-α (TNF-α) plasma concentration in Croatian patients, and to conduct an updated meta-analysis. METHODS: This cross-sectional study enrolled 81 patients with rheumatoid arthritis and 94 control patients. After the assessment of the Disease Activity Score (DAS)-28, blood was taken for analysis. DNA was isolated from the whole blood to determine FasL polymorphism (rs763110) by polymerase chain reaction. Protein levels of TNF-α were determined with ELISA. After a detailed literature search, we conducted an updated meta-analysis using the Review Manager 5 software. RESULTS: Rheumatoid arthritis patients had significantly higher TNF-α concentration in plasma (1.65 [1.2-2.42] pg/mL) than controls (0.99 [0.77-1.35] pg/mL, P<0.001). The FasL rs763110 polymorphism was not associated with rheumatoid arthritis occurrence in either codominant, dominant, recessive, overdominant, or log additive model. Furthermore, the rs763110 genotype was not associated with DAS 28 score or TNF-α concentration. After we added our results to an updated meta-analysis, the significant association previously reported for Western Eurasians was abolished. CONCLUSION: Our data suggest that the association between FasL rs763110 polymorphism and RA susceptibility in Western Eurasians observed in previous studies might be overestimated and should be limited to the population of Southwestern Asia until further investigations are performed.

Chemokine signals are crucial for enhanced homing and differentiation of circulating osteoclast progenitor cells.

BACKGROUND: The peripheral blood (PB) monocyte pool contains osteoclast progenitors (OCPs), which contribute to osteoresorption in inflammatory arthritides and are influenced by the cytokine and chemokine milieu. We aimed to define the importance of chemokine signals for migration and activation of OCPs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: PB and, when applicable, synovial fluid (SF) samples were collected from 129 patients with RA, 53 patients with PsA, and 110 control patients in parallel to clinical parameters of disease activity, autoantibody levels, and applied therapy. Receptors for osteoclastogenic factors (CD115 and receptor activator of nuclear factor-κB [RANK]) and selected chemokines (CC chemokine receptor 1 [CCR1], CCR2, CCR4, CXC chemokine receptor 3 [CXCR3], CXCR4) were determined in an OCP-rich subpopulation (CD3-CD19-CD56-CD11b+CD14+) by flow cytometry. In parallel, levels of CC chemokine ligand 2 (CCL2), CCL3, CCL4, CCL5, CXC chemokine ligand 9 (CXCL9), CXCL10, and CXCL12 were measured using cytometric bead array or enzyme-linked immunosorbent assay. Sorted OCPs were stimulated in culture by macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand, and they were differentiated into mature osteoclasts that resorb bone. Selected chemokines (CCL2, CCL5, CXCL10, and CXCL12) were tested for their osteoclastogenic and chemotactic effects on circulatory OCPs in vitro. RESULTS: The OCP population was moderately enlarged among PB cells in RA and correlated with levels of tumor necrosis factor-α (TNF-α), rheumatoid factor, CCL2, and CCL5. Compared with PB, the RANK+ subpopulation was expanded in SF and correlated with the number of tender joints. Patients with PsA could be distinguished by increased RANK expression rather than total OCP population. OCPs from patients with arthritis had higher expression of CCR1, CCR2, CCR4, CXCR3, and CXCR4. In parallel, patients with RA had increased levels of CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10, with significant elevation in SF vs PB for CXCL10. The subset expressing CXCR4 positively correlated with TNF-α, bone resorption marker, and rheumatoid factor, and it was reduced in patients treated with disease-modifying antirheumatic drugs. The CCR4+ subset showed a significant negative trend during anti-TNF treatment. CCL2, CCL5, and CXCL10 had similar osteoclastogenic effects, with CCL5 showing the greatest chemotactic action on OCPs. CONCLUSIONS: In our study, we identified distinct effects of selected chemokines on stimulation of OCP mobilization, tissue homing, and maturation. Novel insights into migratory behaviors and functional properties of circulatory OCPs in response to chemotactic signals could open ways to new therapeutic targets in RA.

Influence of UV radiation on immunological system and occurrence of autoimmune diseases.

During the last three decades scientists worldwide have investigated how ultraviolet radiation (UVR) influences the immune system. The vast majority of the researchers was primarily focused on the local immunomodulatory role of UVR. But today evidence is increasing in favor of plural immune activation and systemic reaction of the organism. Most of the attention is directed toward the regulatory T lymphocytes which are responsible for the local and systemic immunosuppressive response under the impact of sunlight. The role of regulatory T cells in autoimmune diseases is well studied on patients with systemic lupus erythematosus (SLE). Epidemiological research shows a proportional interdependence of latitude and prevalence of autoimmune diseases such as multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM) and rheumatoid arthritis (RA). There is evidence that UVR has direct influence on the level of antibodies against the SNF2-superfamily helicase (Mi-2), distinctive for dermatomyositis (DM). On this basis a hypothesis is established that UVR is a risk factor for DM. A Croatian epidemiologic study o f systemic sclerosis (SSc) gave results consistent with the hypothesis that there is a higher prevalence of SSc in the Mediterranean regions of Croatia. Such discoveries encouraged further studies that found that not only regulatory T cells are responsible for a systemic immunosuppressive response, but that there is a complex interactive network of immune cells and mediators such as cytokines, neuropeptides, and chromophores like urocanic acid involved. Present findings require continued research on the importance of UVR on autoimmune disease prevalence and immunopathophysiology. Finally, it is necessary to distinguish whether UVR is a protective factor for some autoimmune diseases or a risk factor for their induction.