Memory CD8 T cells play an important role in the protection against breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether the route of antigen exposure ...impacts these cells at a functional level is incompletely characterized. Here, we compare the memory CD8 T cell response against a common SARS-CoV-2 epitope after vaccination, infection, or both. CD8 T cells demonstrate comparable functional capacity when restimulated directly ex vivo, independent of the antigenic history. However, analysis of T cell receptor usage shows that vaccination results in a narrower scope than infection alone or in combination with vaccination. Importantly, in an in vivo recall model, memory CD8 T cells from infected individuals show equal proliferation but secrete less tumor necrosis factor (TNF) compared with those from vaccinated people. This difference is negated when infected individuals have also been vaccinated. Our findings shed more light on the differences in susceptibility to re-infection after different routes of SARS-CoV-2 antigen exposure.
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•Infection and vaccination against SARS-CoV-2 both favor CD8 TEMRA differentiation•Ex vivo functionality of memory T cells is similar after infection and vaccination•The scope of memory CD8 T cells is larger after infection than after vaccination•Vaccination-induced memory generates secondary effectors with superior functionality
Kavazović et al. compare SARS-CoV-2-specific memory CD8 T cells from people after infection, vaccination, or both. Infection induces a more clonally diverse memory pool than vaccination, but these cells produce less TNF after in vivo recall. Subsequent vaccination negates differences, stressing the importance of boosting irrespective of antigenic history.
•Type 2 diabetes is associated with increased tumor necrosis factor-α by CD8 T cells.•Increased granzyme B production by natural killer cells and γδ T cells is observed in type 2 ...diabetes.•Hyperresponsiveness of cytotoxic blood lymphocytes is associated with age and diabetes duration.
Inflammageing, the age-related systemic increase of proinflammatory factors, has been linked to the development of cardiovascular disease, chronic kidney disease and cancer in the elderly. Chronic inflammation is believed to be a causative factor in the development of diabetic complications. However, exactly how type 2 diabetes impacts the inflammatory state of the immune system is incompletely characterised.
Blood collection and anthropometric measurements were performed in patients with type 2 diabetes (n = 49) and control subjects (n = 30). The phenotype, proliferation capacity and cytokine production by cytotoxic lymphocytes were analysed using multiparametric flow cytometry.
Type 2 diabetes did not impact the phenotype or proliferation of the investigated cells. However, we observed a significantly increased production of tumour necrosis factor-α by CD8+ T cells and Granzyme B by natural killer cells and γδ T cells compared to controls. Hyperresponsiveness of cytotoxic blood lymphocytes did not correlate with glycaemia or body mass index, but instead was associated with older age and longer diabetes duration.
Type 2 diabetes is associated with an increased pro-inflammatory potential of cytotoxic blood lymphocytes correlating with age and diabetes duration. Further research is necessary to explore potential benefits of diabetes medications in reverting this effect.
The recent pandemic of COVID-19 has made abundantly clear that Type 2 diabetes (T2D) increases the risk of more frequent and more severe viral infections. At the same time, pro-inflammatory cytokines ...of an anti-viral Type-I profile promote insulin resistance and form a risk factor for development of T2D. What this illustrates is that there is a reciprocal, detrimental interaction between the immune and endocrine system in the context of T2D. Why these two systems would interact at all long remained unclear. Recent findings indicate that transient changes in systemic metabolism are induced by the immune system as a strategy against viral infection. In people with T2D, this system fails, thereby negatively impacting the antiviral immune response. In addition, immune-mediated changes in systemic metabolism upon infection may aggravate glycemic control in T2D. In this review, we will discuss recent literature that sheds more light on how T2D impairs immune responses to viral infection and how virus-induced activation of the immune system increases risk of development of T2D.
Vitamin D i koža Gašparini, Dora; Kaštelan, Marija
Medicina fluminensis,
12/2021, Letnik:
57, Številka:
4
Journal Article
Recenzirano
Povezanost vitamina D i kože započinje sintezom vitamina D u koži, a neprestano se istražuju i uočavaju novi mehanizmi kojima najistraživaniji vitamin utječe na najveći organ ljudskoga tijela. Cilj ...je ovoga rada dati pregled dosadašnjih spoznaja o interakciji vitamina D i kože te utjecaju razina vitamina D na kožne bolesti. Po nekim istraživanjima suboptimalne razine vitamina D nalaze se u čak 30 – 90 % stanovništva, a procjenjuje se da postoji manjak vitamina D u oko jedne milijarde ljudi na cijelome svijetu. U 25,6 – 68 % pacijenata sa psorijazom postoji nedostatak vitamina D, a manjak vitamina D nazočan je u čak 97 % pacijenata. Nadalje, niz opservacijskih studija i metaanaliza dokazalo je da su serumske razine kalcidiola niže u djece i odraslih s atopijskim dermatitisom, a pojedina istraživanja dokazala su da u čak 70,5 % pacijenata s vitiligom postoji nedostatak vitamina D. Niske razine vitamina D povezuju se i s progresijom malignog melanoma, no nepoznato je u kojem trenutku izloženosti UV zračenju vitamin D prestaje djelovati protektivno i započinje biti rizični čimbenik za razvoj tumora kože. Unatoč brojnim provedenim istraživanjima, još uvijek nije poznata priroda odnosa vitamina D i pojedinih kožnih bolesti, odnosno je li on uzročnoposljedičan ili slučajan, dok se u drugih dermatoza, poput psorijaze, dokazi o povezanosti s razinom vitamina D primjenjuju u svakodnevnom radu s pacijentima – u dijagnostici i liječenju.
The relationship between vitamin D and the skin starts with the synthesis of vitamin D in the skin. New mechanisms on how the most researched vitamin affects the biggest organ in the human body are constantly investigated and observed. The aim is to review the current knowledge on vitamin D and skin interaction, as well as the effect of vitamin D levels on skin diseases. According to some studies, suboptimal vitamin D levels are found in as many as 30 – 90% of the population, with an estimated vitamin D insufficiency in about one billion people worldwide. In 25.6 – 68% of patients with psoriasis, there is a deficiency of vitamin D and insufficiency of vitamin D in as many as 97% of patients. Furthermore, a series of observational studies and meta-analyses have shown that the serum levels of calcidiol are lower in children and adults with atopic dermatitis, and some studies have shown that up to 70.5% of patients with vitiligo have vitamin D deficiency. Low levels of vitamin D are associated with the progression of malignant melanoma, but it is unknown at which point UV exposure ceases to be protective through vitamin D and begins to be a risk factor for the development of skin tumours. Despite many studies that have been conducted, the nature of the relationship between vitamin D and certain skin diseases is still unknown, whether it is causal or accidental, while in others, such as psoriasis, evidence of the correlation with vitamin D levels is used in daily work with patients – in diagnosis and treatment.
Cilj: Prikazati slučaj pacijenta s pityriasis lichenoides et varioliformis acuta, s predstavljanjem dijagnostičkih i terapijskih izazova ovog kliničkog entiteta. Prikaz slučaja: Tridesetogodišnji ...pacijent upućen je na Kliniku za dermatovenerologiju zbog kožnih promjena popraćenih svrbežom u trajanju od mjesec i pol dana. Crvene papule i papulokruste bile su prisutne na trupu, gornjim i donjim ekstremitetima, no na gornjim i donjim ekstremitetima bile su brojnije i jače izražene nego na trupu. Pacijent je naveo da je povremeno uzimao febuksostate za liječenje kronične hiperuricemije tijekom posljednje četiri godine. Započeta je lokalna terapija kombinacijom betametazona i gentamicina te peroralnim desloratadinom. U krvnoj slici uočene su neutropenija, povišene vrijednosti kolesterola lipoproteina niske gustoće i povišene vrijednosti urata. Učinjena je biopsija kožne promjene, a pacijentu je preporučen doksiciklin uz nastavak liječenja betametazonom i gentamicinom. Patohistološki nalaz opisivao je ulcerirani epidermis s edemom, granulacijskim tkivom i ekstravazacijom eritrocita u dnu ulceracije. Prema bazi ulceracije i subepidermalno nalazili su se infiltrati limfocita i histiocita, a epidermis je na rubovima ulceracije bio nepravilno hiperplastičan s izraženom spongiozom. Time je potvrđena dijagnoza pityriasis lichenoides et varioliformis acuta. Po završetku liječenja doksiciklinom došlo je do potpune regresije kožnih promjena i sniženja vrijednosti urata. Zaključci: U pacijenata s dijagnozom pityriasis lichenoides et varioliformis acuta potreban je povećan oprez u dijagnosticiranju i liječenju te redovito praćenje stanja zbog širokog spektra diferencijalnih dijagnoza i mogućnosti postavljanja krive dijagnoze. Nužna su daljnja istraživanja o etiopatogenetskoj osnovi ove bolesti s ciljem upotrebe tih znanja u uspješnijem liječenju.
Aim: To report a case of a patient with pityriasis lichenoides et varioliformis acuta, emphasising the challenges in the diagnosis and treatment of this clinical entity. Case report: A 30-year-old patient was referred to the Department of Dermatology and Venereology due to skin changes accompanied by itching persisting for one and a half month. Red papules and papulocrusts were found on the trunk, upper and lower limbs, but in a larger number and more severely affecting the trunk than the limbs. The patient stated the occasional use of febuxostat for the treatment of chronic hyperuricemia that has been diagnosed four years prior. Treatment with desloratadine and a combination of bethametasone and gentamicin was started. The laboratory results showed neutropenia, high levels of low density lipoprotein cholesterol and high levels of urate. The biopsy of the skin lesion has been done. Doxycycline treatment and continuing treatment with bethametasone and gentamicin were recommended to the patient. Pathohistological finding described ulcerated epidermis with oedema, granulation tissue and erythrocyte extravasation in the floor of the ulceration. Lymphocytic and histiocytic infiltrates were found in the base of the ulceration and subepidermally. The epidermis on the edge of the ulceration was irregularly hyperplastic and showed spongiosis. The diagnosis of pityriasis lichenoides et varioliformis acuta has been confirmed. Upon completion of doxycycline treatment skin changes were in regression and urate levels decreased. Conclusions: Not only caution in diagnosis and treatment, but also regular follow-up is necessary in patients diagnosed with pityriasis lichenoides et varioliformis acuta because of a wide range of differential diagnoses and a possibility of misdiagnosis. Further research on the etiopathogenesis of this disorder is needed in order to improve treatment outcomes.
Psorijaza je jedna od najčešćih kroničnih kožnih bolesti s prevalencijom od 1,6 – 3 % u općoj populaciji, stoga je ta bolest vrlo važan javnozdravstveni problem. Riječ je o upalnom imunosno ...posredovanom poremećaju koji se na koži očituje eritematoskvamoznim plakovima na predilekcijskim mjestima. Psorijaza nije životno ugrožavajuća bolest, ali kardiovaskularni rizični čimbenici povezani s njom mogu dovesti do letalnog ishoda. Metabolički sindrom češće se dijagnosticira u pacijenata sa psorijazom u odnosu na opću populaciju, i to ponajviše u pacijentica starijih od 40 godina koje dugo boluju od teškog oblika bolesti. Etiologija razvoja metaboličkih poremećaja nije još u potpunosti razjašnjena, ali postoje dokazi da metaboličke promjene nisu isključivo posljedica dugotrajno aktivne kožne bolesti, već da i prethode prvoj pojavi bolesti. Imunosni odgovor posredovan T-pomoćničkim (engl. T helper, Th) Th1 i Th17 limfocitima sustavno prisutan u pacijenata sa psorijazom pridonosi razvoju ili pogoršanju šećerne bolesti, arterijske hipertenzije i pretilosti. Terapija psorijaze temelji se na liječenju kožne bolesti i komorbiditeta, a prilagođena je pojedinom pacijentu. Primjena metotreksata i bioloških lijekova poput infliksimaba, adalimumaba i etanercepta povezana je s nižim stopama mortaliteta, infarkta miokarda i moždanog udara te s poboljšanjem endotelne funkcije u odnosu na pacijente liječene drugim terapijskim mogućnostima. Pristup pacijentu sa psorijazom mora biti sveobuhvatan i multidisciplinaran te uključivati liječenje psorijaze uz prevenciju, rano prepoznavanje i odgovarajuće liječenje komorbiditeta.
Psoriasis is one of the most common chronic skin diseases with the prevalence of 1.6-3% in general population, therefore it is an important public health issue. It is an inflammatory immunomediated disorder that manifests as a eritematosquamous dermatosis with plaques on predilection areas. Psoriasis is not a life-threatening disease itself, however cardiovascular risk factors connected to it may lead to a lethal outcome. Metabolic syndrome is diagnosed in patients with psoriasis more often than in general population, especially in female patients older than 40 years old with a longer and more severe form of psoriasis. Etiology of the metabolic changes is still not completely understood, although there is evidence that metabolic changes are not exclusively the result of long active disease, but can precede the first onset of symptoms. T helper (Th) Th1- and Th17-cells-mediated immunological response systemically present in psoriasis contributes to the development or deterioration of diabetes mellitus, high blood pressure and obesity. Treatment of psoriasis is based on the management of skin disease and its comorbidities adjusted to individual patient. Use of methotrexate and biological agents such as infliximab, adalimumab and etanercept has shown lower rates of mortality, myocardial infarction and stroke with improvement of endothelial function in regards to patients treated with other therapeutical options. Approach to a patient suffering from psoriasis needs to be comprehensive and multidisciplinary, involving the management of psoriasis, prevention, early diagnosis and adequate management of its comorbidities.
Chronic pain is a painful condition defined by its duration where pain persists three months or more. Pain is connected with the high price of health care, work inability and disability. Moreover, it ...has significant consequences for patients and their families, working organizations and the society as a whole. The prevalence of chronic pain can range between 11.0% and 51.3% in general population. Pain is usually coherent with distress and a range of psychological symptoms such as depression, anxiety, altered attention and cognition manifesting as fear. Comprehensive pain management should always include the treatment of associated psychological symptoms. Multidisciplinary approach in treating chronic pain and its comorbidities and proper education of primary care physicians and different specialists involved in the management of chronic pain are crucial for better clinical outcomes. Topical capsaicin acts as a highly selective agonist of transient receptor potential vanilloid 1 of C and Aδ nociceptors. Repeated applications or high concentrations give rise to a long-lasting effect termed defunctionalisation. In addition, the reduction of central sensitization through reduced C-nociceptor input contributes to capsaicin's indirect mechanism of action. Capsaicin provides effective durable pain relief and reduction of intensity and area of pain in adult patients with chronic pain with a faster onset of analgesia and considerably fewer systemic adverse effects than the conventional treatment. While offering high levels of pain relief, additional improvements in sleep, fatigue, depression and quality of life have been noticed. Topical administration avoids dangerous systemic adverse effects and enables the combination with other drugs and analgesics with limited drug-drug interactions. Adding capsaicin to the standard chronic pain treatment might improve, fasten and ease the challenging path of managing chronic pain consequently providing the patient and their society with better quality of life.
Amiodarone is a potent antiarrhythmic medication used to treat life-threatening ventricular arrhythmias; however, its well-established adverse effect is a thyroid disorder. Amiodarone-induced ...thyroiditis (AIT), a clinical entity involving two types with different etiopathology and treatment approaches, may occur at the beginning or even several years after amiodarone treatment discontinuation. The toxicity profile of amiodarone becomes especially important in young patients with lifelong cardiac disorders, which are often refractory to other antiarrhythmic drugs. Herein, we report the first case of non-sustained ventricular tachycardia (NSVT), an unusual presentation of type II AIT, in a young male patient who was previously diagnosed with left ventricular cardiomyopathy with excessive trabeculation.
A 36-year-old male non-athlete presented with tiredness during regular follow-up. Continuous electrocardiographic monitoring (cECG) revealed NSVT, whereas echocardiography and cardiac magnetic resonance imaging detected discrete structural and functional changes that could not fully explain the observed cECG report. Conversely, an unmeasurably low thyrotropin level on admission and previous exposure to amiodarone pointed the diagnostic pathway in the direction of the thyroid gland. Elevated free thyroxine and undetectable autoantibody titers with unremarkable sonographic findings raised clinical suspicion of type II AIT. Scintigraphic imaging with
Tc-2-methoxyisobutylisonitrile (sestamibi) revealed decreased thyroid uptake; hence, prednisone was introduced for treatment. Clear improvements in both biochemical and electrocardiographic parameters were observed after immunomodulatory treatment of type II AIT in this young patient with cardiomyopathy and excessive trabeculation.
Treatment of reversible causes of cardiac rhythm abnormalities such as type II AIT should be considered before choosing other treatment modalities, particularly in patients with structural cardiac disorders. The importance of a multidisciplinary approach in complex cases such as the one reported, thus, cannot be emphasized enough.
•Elite Freedivers do not display major changes in their immunological profile compared to non-diving controls under resting conditions.•Following an extreme freedive, CD8 T cells, NK cells and δ1+ γδ ...T cells downregulate expression of cytotoxic molecules.•Following an extreme freedive, CD8 T cells, NK cells and δ2+ γδ T cells have an increased potential to produce IFNγ and TNF.•Changes in the immunological profile of cytotoxic immune cells following a freedive are associated with psychological stress, hypoxia and changes in glucose levels.•Following extreme anaerobic exercise, the cytotoxic arm of the immune system undergoes changes that reduces its possibility to cause tissue damage, but increase its ability to signal threats, possibly as an acute adaptation mechanism.
Exercise has many beneficial effects for our body, but can become detrimental at high intensity, especially for our immune system. Little is known about the underlying mechanism of impaired immune functionality under conditions of intense physical strain. Freedivers, people who dive to high depths on a single breath, perform extreme exercise under anaerobic conditions. In this study, we investigated the impact of freediving on the cytotoxic arm of the immune system. At rest, elite freedivers did not display changes in their immunological profile compared to non-diving controls. In contrast, after a freedive, granzyme B and IL-2 production were reduced, whereas IFNγ and TNF secretion were increased by cytotoxic immune cells. Using in vitro models mimicking freedive conditions, we could show that hypoxia in combination with stress hyperglycemia had a negative impact on Granzyme B secretion, whereas IL-2 production was inhibited by stress hormones. Our findings suggest that in response to extreme exercise, cytotoxic immune cells transiently change their functional profile to limit tissue damage.
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