The Interrelationship between Sarcoidosis and Atherosclerosis—Complex Yet Rational

Sarcoidosis is a systemic inflammatory disease of unknown etiology, characterized by the presence of non-caseating granulomas in affected organs [...]

Differential Macrophage Phenotype Rewired by Hantaan Virus Constrains the Magnitude of Inflammatory Responses in Murine versus Humans

Hantaan virus (HTNV) is principally maintained and transmitted by rodents in nature, the infection of which is non-pathogenic in the field or laboratory mouse, but can cause hemorrhagic fever with renal syndrome (HFRS) in human beings, a severe systemic inflammatory disease with high mortality. It remains obscure how HTNV infection leads to disparate outcomes in distinct species. Here, we revealed a differential immune status in murine versus humans post HTNV infection, which was orchestrated by the macrophage reprogramming process and characterized by late-phase inactivation of NF-κB signaling. In HFRS patients, the immoderate and continuous activation of inflammatory monocyte/macrophage (M1) launched TNFα-centered cytokine storm and aggravated host immunopathologic injury, which can be life-threatening; however, in field or laboratory mice, the M1 activation and TNFα release were significantly suppressed at the late infection stage of HTNV, restricting excessive inflammation and blocking viral disease process, which also protected mice from secondary LPS challenge or polymicrobial sepsis. Mechanistically, we found that murine macrophage phenotype was dynamically manipulated by HTNV via the Notch-lncRNA-p65 axis. At the early stage of HTNV infection, the intracellular domain of Notch receptor (NICD) was activated by viral nucleocapsid (NP) stimulation and potentiated the NF-κB pathway by associating with and facilitating the interaction between IKKβ and p65. At the late stage, Notch signaling launched the expression of diverse murine-specific long non-coding RNAs (lncRNAs) and attenuated M1 polarization. Among them, lncRNA 30740.1 (termed as lnc-ip65, an inhibitor of p65) bound to p65 and hindered its phosphorylation, exerting negative feedback on the NF-κB pathway. Genetic ablation of lnc-ip65 shifted the balance of macrophage polarization from a pro-resolution to an inflammatory phenotype, leading to superabundant production of pro-inflammatory cytokines and increasing mice susceptibility to HTNV infection or bacterial sepsis. Collectively, our findings identify an immune braking function and mechanism for murine lncRNAs in inhibiting p65-mediated M1 activation, opening a novel therapeutic avenue of controlling the magnitude of immune responses for HFRS and other inflammatory diseases.

The Role of Lung Ultrasound in Diagnosing COVID-19-Related Multisystemic Inflammatory Disease: A Preliminary Experience

Background: To date, there are no data regarding the systematic application of Point-of-Care Lung Ultrasound (PoC-LUS) in children with Multisystem Inflammatory Syndrome in Children (MIS-C). The main aim of this study is to show the role of Point-of-Care Lung Ultrasound as an additional aid in the diagnosis of COVID-19-related Multisystem Inflammatory Syndrome in Children (MIS-C). Methods: Between April 2020 and April 2021, patients aged 0–18 years referred to our emergency department for fever, and later hospitalized without a specific diagnosis, underwent PoC-LUS. Ultrasound images of patients with a final diagnosis of MIS-C were retrospectively evaluated. Results: Ten patients were enrolled. All were described to have pleural irregularities and B-lines. In particular: 8/10 children presented with isolated B-lines in at least half of the lung areas of interest; 8/10 presented with multiple B-lines and 3/8 had them in at least 50% of lung areas; 5/10 had a white lung appearance in at least one lung area and 1/5 had them in half of the areas of interest. Pleural effusion was described in 9/10. Conclusions: During the ongoing COVID-19 pandemic, we suggest performing PoC-LUS in febrile patients with high levels of inflammatory indices and clinical suspicion of MIS-C, or without a certain diagnosis; the finding of many B-lines and pleural effusion would support the diagnosis of a systemic inflammatory disease.

Anti-CCP antibody in rheumatoid arthritis patients and its relation with severity of the disease

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by chronic and erosive polyarthritis causing irreversible joint disability. It is the most common persistent inflammatory arthritis, affecting from 0.5 to 1% of the general population worldwide. Antibodies to citrullinated proteins (anti-CCP antibody) have been described in patients with RA and these appear to be the most specific marker of the disease. Methods: This cross-sectional study was carried out at department of medicine, Sher-E-Bangla Medical College Hospital, Barisal Form July’ 2016 to December’ 2016. All rheumatoid arthritis patients attending at OPD and those got admitted under Medicine Dept, who was satisfying the inclusion and exclusion criteria were included consecutively and purposively in this study. Results: Total 70 cases were included; the mean age was found 46.57±13.10 years in anti-CCP antibody positive group and 44.19±11.21 years in anti-CCP antibody negative group. Female were predominant in both groups. Duration of disease was around 8 years in both groups. Mean ESR was 29.0±22.0 mm in anti-CCP antibody positive group and 12.25±10.6 mm in anti-CCP antibody negative group. Mean rheumatoid factor was 189.4±102.1 U/L in anti-CCP antibody positive group and 66.5±36.0 U/L in anti-CCP antibody negative group. Mean DAS 28 score was 4.6±1.4 and 3.6±1.3 in anti-CCP antibody positive and negative group respectively. The mean difference was statistically significant (p<0.05) between the groups. Patients in disease remission had lower anti-CCP antibody titer than those with low, moderate or high disease activity. Significantly positive correlation (r=0.596; p=0.001) between severity of rheumatoid arthritis and anti CCP antibody level was observed. Conclusion: In RA patients’ disease was more severe in anti-CCP antibody positive group and significantly positive correlation between anti-CCP antibody level with disease severity of RA was observed. BIRDEM Med J 2022; 12(1): 36-40

A System-Level Mechanism of Anmyungambi Decoction for Obesity: A Network Pharmacological Approach

Obesity is a low-grade systemic inflammatory disease involving adipocytokines. As though Anmyungambi decoction (AMGB) showed significant improvement on obesity in a clinical trial, the molecular mechanism of AMGB in obesity remains unknown. Therefore, we explored the potential mechanisms of action of AMGB on obesity through network pharmacological approaches. We revealed that targets of AMGB are significantly associated with obesity-related and adipocyte-elevated genes. Evodiamine, berberine, genipin, palmitic acid, genistein, and quercetin were shown to regulate adipocytokine signaling pathway proteins which mainly involved tumor necrosis factor receptor 1, leptin receptor. In terms of the regulatory pathway of lipolysis in adipocytes, norephedrine, pseudoephedrine, quercetin, and limonin were shown to affect adrenergic receptor-beta, protein kinase A, etc. We also found that AMGB has the potentials to enhance the insulin signaling pathway thereby preventing type II diabetes mellitus. Additionally, AMGB was discovered to be able to control not only insulin-related proteins but also inflammatory mediators and apoptotic regulators and caspases, hence reducing hepatocyte injury in nonalcoholic fatty liver disease. Our findings help develop a better understanding of how AMGB controls obesity.

Adult-Onset Still’s Disease: Novel Biomarkers of Specific Subsets, Disease Activity, and Relapsing Forms

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disease of unknown etiology. Recent studies have demonstrated that the hallmark of AOSD is a cytokine storm, which is characterized by the excessive production of interleukin (IL)-1, IL-6, IL-18, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), suggesting how pro-inflammatory cytokines play an important role in the pathogenesis of this disease. Actually, a certain proportion of patients (around 17–32%) with severe clinical symptoms achieves only partial remission or is resistant to both first-line corticosteroids and second-line DMARDs. These patients are defined as refractory AOSD patients, requiring higher dosage glucocorticoids, longer treatment duration, or the simultaneous introduction of immunosuppressive drugs, further leading to AOSD relapses. In this narrative review, we will analyze the latest literature data to unravel potential pathogenetic factors associated with specific patterns of AOSD disease or relapses in order to identify biomarkers that may guide clinical decisions, eventually leading to new therapeutic options.

Insulin resistance in patients with psoriasis

Psoriasis is a chronic systemic inflammatory disease accompanied by an activation of skin dendritic cells with accumulation in the inflammatory foci of interleukin-23 and activated Th-1 lymphocytes (Th-17, Th-22). In recent years, there has been a large number of evidence linking psoriasis with other inflammatory diseases, including obesity, diabetes mellitus, atherosclerosis, hypertension, nonalcoholic fatty liver disease, polycystic ovary syndrome, benign prostatic hyperplasia, etc. All of these conditions are associated with systemic inflammation and insulin resistance induced by it. Psoriasis is the most common chronic dermatosis and affects 1–2 % of the population in developed countries. Psoriasis as a chronic immune-mediated inflammatory skin disease is often associated with metabolic syndrome and its components such as obesity, hypertension, insulin resistance and dyslipidemia. The risk of developing metabolic syndrome in patients with psoriasis is 40 % higher than in the general population. Psoriasis and metabo­lic syndrome share some pathogenic mechanisms such as chronic low-grade systemic inflammation and an increased level of pro-inflammatory cytokines. Systemic inflammation causes obesity, cardiovascular diseases, diabetes mellitus type 2. These conditions increase the risk of mortality among patients with psoriasis. There is a positive correlation between the severity of psoriasis and metabolic syndrome, which is manifested by a severe rash, reduction of the remission and higher risk of psoriatic arthritis development. The carriers of the risk allele of FTO gene are characterized by a more severe psoriasis, the presence of psoriatic arthritis and increased body mass index. A review of the literature focuses on the relationship between insulin resistance and the pathogenesis of psoriasis.

Usefulness of position emission tomography/computed tomography in a case of sarcoidosis with multiorgan involvement

Sarcoidosis, a systemic inflammatory disease of unknown etiology, can affect any site in the body. A bone lesion was unexpectedly detected by fluorodeoxyglucose position emission tomography/computed tomography (FDG PET/CT) in a patient with multiorgan sarcoidosis. FDG PET/CT should be considered for the detection of clinically silent lesions of sarcoidosis.

The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines released by dendritic, Th1, Th2, and Th17 cells leads to the phenotypical manifestations seen in psoriasis. Biological therapies target the cytokine-mediated pathogenesis of psoriasis and have improved patient quality of life. This review will describe the underlying molecular pathophysiology and biologics used to treat psoriasis. A review of the literature was conducted using the PubMed and Google Scholar repositories to investigate the molecular pathogenesis, clinical presentation, and current therapeutics in psoriasis. Plaque psoriasis’, the most prevalent subtype of psoriasis, pathogenesis primarily involves cytokines TNF-α, IL-17, and IL-23. Pustular psoriasis’, an uncommon variant, pathogenesis involves a mutation in IL-36RN. Currently, biological therapeutics targeted at TNF-α, IL-12/IL-23, IL-17, and IL-23/IL-39 are approved for the treatment of moderate to severe psoriasis. More studies need to be performed to elucidate the precise molecular pathology and assess efficacy between biological therapies for psoriasis. Psoriasis is a heterogenous, chronic, systemic inflammatory disease that presents in the skin with multiple types. Recognizing and understanding the underlying molecular pathways and biological therapeutics to treat psoriasis is important in treating this common disease.

Recommendations of the Brazilian Society of Rheumatology for the use of JAK inhibitors in the management of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic and autoimmune systemic inflammatory disease that can cause irreversible joint deformities, with increased morbidity and mortality and a significant impact on the quality of life of the affected individual. The main objective of RA treatment is to achieve sustained clinical remission or low disease activity. However, up to 40% of patients do not respond to available treatments, including bDMARDs. New therapeutic targets for RA are emerging, such as Janus kinases (JAKs). These are essential for intracellular signaling (via JAK-STAT) in response to many cytokines involved in RA immunopathogenesis. JAK inhibitors (JAKi) have established themselves as a highly effective treatment, gaining increasing space in the therapeutic arsenal for the treatment of RA. The current recommendations aim to present a review of the main aspects related to the efficacy and safety of JAKis in RA patients, and to update the recommendations and treatment algorithm proposed by the Brazilian Society of Rheumatology in 2017.