Autoimmune Inflammatory Disease Research Articles

Uveitis and Scleritis as a Risk Factor for Mortality

ABSTRACT Purpose Uveitis and scleritis may be caused by local or systemic infection, or associated with noninfectious systemic inflammatory autoimmune disease. This study explored the all-cause mortality following an individual’s first presentation with uveitis/scleritis. Methods A cross-sectional study was conducted on all uveitis/scleritis patients diagnosed by uveitis specialists and treated in a single tertiary referral center in New Zealand between 2006 and 2020(15y). Masquerade syndromes including intraocular lymphoma were excluded. Outcome measures: demographics, etiology of uveitis/scleritis, anatomical location and all-cause mortality. Results 2723 subjects were identified. Median age of onset of uveitis/scleritis was 44.9 years (Range:1.5–99.5 years). 49.6% were female. Median follow-up from diagnosis of uveitis/scleritis was 8.0 years (IQR 4.1–11.6 years) with a total follow-up of 24 443.3 subject-years. The most frequent diagnosis was idiopathic disease (30.9%), HLA-B27-positive uveitis (20.0%), and sarcoidosis (4.7%). Infectious etiologies (24.1%) were most commonly from herpes zoster virus (9.3%) and toxoplasmosis (4.3%). The age-adjusted mortality rate was higher in subjects with idiopathic disease, sarcoidosis, Fuchs’ uveitis syndrome, granulomatosis with polyangiitis/ANCA-associated vasculitis, toxoplasmosis, and herpes zoster virus, when compared to HLA-B27-positive uveitis. Hazard of mortality peaked in the first seven years following diagnosis, then subsequently declined. Patients with uveitis/scleritis had a significantly higher rate of mortality compared to the general New Zealand population (IRR 1.656 p = 0.017). Conclusion Infectious etiologies of uveitis/scleritis in this cohort were high when compared to other developed nations, attributable to data from a tertiary referral center treating inpatients. Potential shared inflammatory mechanisms in the eye and other organs can lead to concurrent non-ocular disease requiring systemic treatment, impacting an individual’s longevity.

NRF2 Plays a Crucial Role in the Tolerogenic Effect of Ethyl Pyruvate on Dendritic Cells.

Ethyl pyruvate (EP) is a redox-active compound that has been previously shown to be effective in restraining immune hyperactivity in animal models of various autoimmune and chronic inflammatory diseases. Importantly, EP has also been proven to have a potent tolerogenic effect on dendritic cells (DCs). Here, the influence of EP on the signaling pathways in DCs relevant for their tolerogenicity, including anti-inflammatory NRF2 and pro-inflammatory NF-κB, was explored. Specifically, the effects of EP on DCs obtained by GM-CSF-directed differentiation of murine bone marrow precursor cells and matured under the influence of lipopolysaccharide (LPS) were examined via immunocytochemistry and RT-PCR. EP counteracted LPS-imposed morphological changes and down-regulated the LPS-induced expression of pro-inflammatory mediators in DCs. While it reduced the activation of NF-κB, EP potentiated NRF2 and downstream antioxidative molecules, thus implying the regulation of NRF2 signaling pathways as the major reason for the tolerizing effects of EP on DCs.

Effectiveness of Biologic Therapy in Controlling Inflammation and Achieving Disease Remission in Patients with Rheumatoid Arthritis: A Systematic Review

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder characterized by joint pain, swelling, and potential systemic complications. The usefulness of biological treatments in reducing inflammation and helping RA patients achieve clinical remission is assessed in this systematic narrative review. Using PubMed, Scopus, and Google Scholar, a thorough literature search was carried out with an emphasis on research published in the last five years. The inclusion criteria were English-language human subject research that contributed significantly to our understanding of biological therapies for RA. Despite concerns over long-term drug withdrawal, TNF-alpha inhibitors, including certolizumab, adalimumab, and infliximab, have shown considerable effectiveness in lowering disease activity and inducing remission. Tocilizumab and other IL inhibitors have shown strong anti-inflammatory properties and increased rates of medication retention. Certain patient profiles have shown success with other biologics, such as rituximab and abatacept, especially those who have not responded to previous therapies. Empirical evidence demonstrates that tofacitinib, a JAK inhibitor, is just as effective as conventional biologics. The study emphasizes how important it is to create individualized treatment programs depending on the medical history and response to the condition. Even with encouraging findings, improving RA care requires ongoing observation of safety profiles and long-term effects. This study offers a thorough synthesis of the available data to help physicians choose the best biologic therapy for patients with RA.

Validation of Methotrexate Intolerance Severity Score (MISS) questionnaire to measure methotrexate intolerance among rheumatoid arthritis Egyptian patients

BackgroundRheumatoid arthritis (RA) is a systemic autoimmune chronic inflammatory disease, causing progressive disability. Methotrexate (MTX) is the gold standard drug treatment for RA. Long-term use of MTX is associated with intolerance including gastrointestinal effects. In addition, anticipatory, associative, and behavioral symptoms such as anxiety and irritability are also observed which are often inadequately managed, leading to discontinuation of treatment. Methotrexate Intolerance Severity Score (MISS) questionnaire designed to measure MTX intolerance. The work aims to validate the MISS questionnaire Arabic version for the detection of MTX intolerance among Egyptian RA patients to halt the progression of the disease.ResultsA total of 80 patients were involved in this study. Of those, 67 (83.8%) were females with a mean disease duration of 6.9 ± 6.1 years. Forty-eight patients (60%) were intolerant to MTX and 32 patients (40%) were tolerant. Comparison between the tolerant group (n = 32) to MTX and the intolerant group (n = 48) revealed a statistically significant difference between them regarding the DAS28 score and HAQ score. Behavioral intolerance is the predominant factor that directs MTX intolerance.ConclusionThe MISS questionnaire has a good predictive ability to detect MTX intolerance among Egyptian RA patients. Due to its good reliability, serves as an invaluable tool as it detects anticipatory and associative symptoms.

The Impact of Climate Change on Immunity and Gut Microbiota in the Development of Disease.

According to the definition provided by the United Nations, "climate change" describes the persistent alterations in temperatures and weather trends. These alterations may arise naturally, such as fluctuations in the solar cycle. Nonetheless, since the 19th century, human activities have emerged as the primary agent for climate change, primarily attributed to the combustion of fossil fuels such as coal, oil, and gas. Climate change can potentially influence the well-being, agricultural production, housing, safety, and employment opportunities for all individuals. The immune system is an important interface through which global climate change affects human health. Extreme heat, weather events and environmental pollutants could impair both innate and adaptive immune responses, promoting inflammation and genomic instability, and increasing the risk of autoimmune and chronic inflammatory diseases. Moreover, climate change has an impact on both soil and gut microbiome composition, which can further explain changes in human health outcomes. This narrative review aims to explore the influence of climate change on human health and disease, focusing specifically on its effects on the immune system and gut microbiota. Understanding how these factors contribute to the development of physical and mental illness may allow for the design of strategies aimed at reducing the negative impact of climate and pollution on human health.

Anti-Müllerian hormone (ovarian reserve) in rheumatoid arthritis patients: correlation with disease activity

BackgroundRheumatoid arthritis is considered one of the most common chronic inflammatory autoimmune diseases that lead to affection of several joints, as well as extra-articular organ involvement.Rheumatoid arthritis women tend to menopause somewhat earlier. This was attributed to primary ovarian insufficiency because of autoimmune disorders. Anti-Müllerian hormone is a marker used for evaluating preantral follicle reserve. It provides a very sensitive way to reflect the ovarian reserve and has become a crucial factor in determining it.The study aimed to show the influence of rheumatoid arthritis and its activity on ovarian reserve assessed using anti-Müllerian hormone serum levels.ResultsOur cross-sectional study involved 30 rheumatoid arthritis female patients with an age range between 25 and 35 years. The Disease Activity Score (DAS 28-ESR) was used to assess the degree of disease activity. Serum level of anti-Müllerian hormone was determined using quantitative enzyme-linked immunosorbent assay and the correlation with the disease activity as well as with the medications the patients were receiving was analyzed. A statistically significant relation was found amid the disease activity and the anti-Müllerian hormone level. Serum levels of anti-Müllerian hormone were found less in cases with high disease activity than in low to moderate cases. Different medications had no effect on anti-Müllerian hormone levels.ConclusionsRheumatoid arthritis high disease activity was linked to a diminished level of serum anti-Müllerian hormone.

Review of current and potential applications of mesenchymal stem cells in exotic animal species.

The discovery that a population of cells derived from adult tissues had regenerative properties and could be expanded and utilized therapeutically led to an abundance of research into the safety and efficacy of these cells for a variety of disease processes. Derived from tissues of mesenchymal origin, these cells were called mesenchymal stem cells or mesenchymal stromal cells (MSCs). MSCs were subsequently found to have a variety of anti-inflammatory, antimicrobial, and regenerative properties both in vitro and in vivo. These cells have been extensively studied and demonstrated to be effective in the treatment of autoimmune diseases, inflammatory diseases, infectious diseases, and other pathologic conditions. Multiple veterinary clinical trials have been performed for diseases such as osteoarthritis, soft tissue, and tendon injuries in addition to other inflammatory and infectious conditions. Exotic animal species can pose additional challenges to the treatment of common medical conditions such as osteoarthritis due to varying metabolism and tolerance to medications as well as potential difficulty to medicate or utilize other common forms of therapy such as physical therapy, laser, massage, and acupuncture. Current knowledge of MSC use in exotic species is limited, but there is a large potential for benefit to a variety of species utilizing this novel therapeutic tool. This review includes a brief overview of mechanisms and known applications of this therapy as well as current and potential applications of MSCs in exotic animal species.

Possible role of β-hydroxybutyrate in inducing inflammation in alopecia areata.

Alopecia areata (AA) is an autoimmune inflammatory disease characterized by non-scarring hair loss due to an immune response that targets hair follicles. The current treatment approach for AA involves the use of immunosuppressants and immunomodulators to reduce cytokine levels around affected hair follicles. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as potential anti-inflammatory agents with diverse beneficial effects in various medical conditions. This study investigates the role of beta-hydroxybutyrate (BHB), a ketone body produced during SGLT2 inhibition, in the pathogenesis of AA. Serum BHB levels were found to be significantly elevated in patients with AA compared with healthy controls, with higher levels correlating with severity of hair loss. BHB treatment increased inflammatory cytokine production in outer root sheath (ORS) cells, mimicking the inflammatory conditions seen in AA. The results suggest that elevated BHB levels may exacerbate the inflammatory immune response in AA patients and may be associated with chronic hair loss and resistance to treatment. Serum BHB levels may serve as a potential marker of poor prognosis in patients with severe AA. Further research is needed to elucidate the precise role of BHB in the pathogenesis of AA and its implications for disease management.

Natural Product-Derived Compounds Targeting Keratinocytes and Molecular Pathways in Psoriasis Therapeutics.

Psoriasis is a chronic autoimmune inflammatory skin disorder that affects approximately 2-3% of the global population due to significant genetic predisposition. It is characterized by an uncontrolled growth and differentiation of keratinocytes, leading to the formation of scaly erythematous plaques. Psoriasis extends beyond dermatological manifestations to impact joints and nails and is often associated with systemic disorders. Although traditional treatments provide relief, their use is limited by potential side effects and the chronic nature of the disease. This review aims to discuss the therapeutic potential of keratinocyte-targeting natural products in psoriasis and highlight their efficacy and safety in comparison with conventional treatments. This review comprehensively examines psoriasis pathogenesis within keratinocytes and the various related signaling pathways (such as JAK-STAT and NF-κB) and cytokines. It presents molecular targets such as high-mobility group box-1 (HMGB1), dual-specificity phosphatase-1 (DUSP1), and the aryl hydrocarbon receptor (AhR) for treating psoriasis. It evaluates the ability of natural compounds such as luteolin, piperine, and glycyrrhizin to modulate psoriasis-related pathways. Finally, it offers insights into alternative and sustainable treatment options with fewer side effects.

Development of Clarstatin, a Novel Drug Lead for the Therapy of Autoimmune Uveitis.

We describe the design, synthesis, and activity of a potent thiourea-bridged backbone cyclic peptidomimetic known as Clarstatin, comprising a 5-amino acid sequence (Q/D)1-(R/K)2-X3-X4-A5-(Gln/Asp)1-(Arg/Lys)2-AA3-AA4-Ala5-based on a motif called "shared epitope (SE)", specifically present in specific alleles of the HLA-DRB1 gene. This SE binds to a particular site within the proline reach domain (P-domain) of the cell surface-calreticulin (CS-CRT). CS-CRT is a multifunctional endoplasmic reticulum (ER) calcium-binding protein that is located on the cell surface of T cells and triggers innate immune signaling, leading to the development of inflammatory autoimmune diseases. The development of Clarstatin was based on the parent peptide W-G-D1-K2-S3-G4-A5- derived from the active region of the SE. Following the design based on the cycloscan method, the synthesis of Clarstatin was performed by the Fmoc solid phase peptide synthesis (SPPS) method, purified by HPLC to 96% homogeneity, and its structure was confirmed by LC-MS. Clarstatin reduced calcium levels in Jurkat lymphocyte cultures, ameliorated uveitis in vivo in the experimental autoimmune uveitis (EAU) mice model, and was safe upon acute toxicity evaluation. These findings identify Clarstatin as a promising lead compound for future drug development as a novel class of therapeutic agents in the therapy of uveitis.

Treatment Discontinuation in Patients with Psoriasis Treated with Biologics: A Retrospective Analysis of German Health Claims Data.

Plaque psoriasis is a common, often debilitating, chronic autoimmune inflammatory skin disease. Moderate-to-severe forms of psoriasis can be treated with biologics such as anti-interleukin and anti-tumor necrosis factor antibodies. We aimed to investigate treatment discontinuation among patients with psoriasis who initiated biologic treatment. We conducted a retrospective, non-interventional cohort study based on anonymized claims data from the German statutory health insurance which covered the years from 2016 to 2021. We included adult patients with psoriasis who initiated biologic treatment in drug-specific cohorts. Over a 365-day follow-up period, we assessed the frequencies and the time until treatment discontinuation for different biologics. Differences in discontinuation rates were compared using a multivariate Cox proportional hazards model. A total of 2565 patients with psoriasis who initiated treatment with secukinumab (n = 612), adalimumab (n = 454), guselkumab (n = 354), ixekizumab (n = 259), ustekinumab (n = 241), tildrakizumab (n = 205), brodalumab (n = 166), risankizumab (n = 145), etanercept (n = 91), certolizumab (n = 29), and infliximab (n = 9) were included. A total of 1290 patients (50.29%) discontinued treatment during the follow-up period, ranging from 30.34% (risankizumab) to 69.23% (etanercept). Median time until discontinuation of treatment ranged from 102days (etanercept) to 208days (risankizumab). Once the biologic treatment was discontinued, 45.05% of patients restarted the treatment with the same agent, 23.10% of patients switched to another biologic, and 31.86% received no further biologic agent. Compared to patients treated with risankizumab, the treatment discontinuation rate was significantly higher (p < 0.05) in patients treated with the other biologics except ustekinumab (p = 0.12). Further research should explore reasons leading to treatment discontinuation in order to support treatment choices for patients with moderate-to-severe psoriasis.

#2324 Do urinary tract infections trigger chronic inflammation in the kidney allograft? Interleukin 17 levels in the urine of kidney recipients

Abstract Background and Aims Urinary tract infections (UTI) represent the most common complication following kidney transplantation. Their role in triggering immune phenomena in kidney allograft remains unclear. Interleukin 17 (IL17) represents the significant branch in antimicrobial immunity. At the same time IL17 has been found associated with autoimmune inflammatory disorders. The triggering role of infections in autoimmunity as well as the similarities between autoimmunity and post-transplant immunity have been postulated. The aim of the study was to analyze the levels of urine IL 17A levels in relation to prior UTI history and the timeframe after the last UTI episode. Method The group of 91 kidney recipients who received kidney transplantation between 2016 and 2019 was analyzed. The set of 233 urine samples (109 from females and 124 from males) obtained within first 24 months post-transplant was investigated, among these 144 samples from the patients with no previous UTI history and 89 samples from the patients with previous UTI history (1-22 months after the last episode, average 6.7 ± SD 5.7). Furthermore, 18 samples obtained at the time of an UTI episode and 29 samples from healthy controls were included. Urine IL 17A levels were measured with Human IL 17 ELISA Kit (Sigma Aldrich) and urine IL/creatinine concentrations ratio was calculated for each value. Szapiro-Wilk test was used to assess data distribution, Kruskal-Wallis test was used to assess the differences between independent groups and two proportions Z test was used to compare the groups compositions. Results Interleukin 17A appeared detectable in 105 out of the 233 investigated samples (45%), with significantly higher frequency in samples from the recipients with previous UTI history (p = 0.02). The difference was not significant in the group who underwent recurrent UTI episodes vs. these after a single UTI episode. Among the samples in which IL 17A was detected, the period between the last UTI episode and sample collection was divided into three timeframes: 1-3 months, 4-12 months and 12-24 months. Urine IL17A levels appeared significantly higher independently in each timeframe post-UTI when compared to the samples from the recipients without UTI history and controls (p = 0.0001). Fig. 1 It was apparent within the whole group but also in males and females separately. Further, urine IL17A levels were significantly higher in males 1-3 months after the last UTI episode than in females in the analogous period (p = 0.001). Conclusion Interleukin 17A was more frequently detected in urine samples from kidney recipients with previous UTI history. UTI history impacted IL17A urine levels in the analyzed kidney recipients. Within the first 24 months post-transplant, these were higher in the recipients with UTI history prior to the sample collection and it was independent on the timeframe between the last UTI episode and the sample collection. The factors other than UTI history which influence urine IL17A detectability are not fully recognized and remain under investigation.

Reassessing granzyme B: unveiling perforin-independent versatility in immune responses and therapeutic potentials

The pivotal role of Granzyme B (GzmB) in immune responses, initially tied to cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, has extended across diverse cell types and disease models. A number of studies have challenged conventional notions, revealing GzmB activity beyond apoptosis, impacting autoimmune diseases, inflammatory disorders, cancer, and neurotoxicity. Notably, the diverse functions of GzmB unfold through Perforin-dependent and Perforin-independent mechanisms, offering clinical implications and therapeutic insights. This review underscores the multifaceted roles of GzmB, spanning immunological and pathological contexts, which call for further investigations to pave the way for innovative targeted therapies.

Pneumocystis pneumonia in French intensive care units in 2013-2019: mortality and immunocompromised conditions.

The recent epidemiology of Pneumocystis pneumonia (PCP) requiring intensive care unit (ICU) admission and the associated spectrum of immunocompromising conditions are poorly described. We analyzed all adult PCP cases admitted to French ICUs via the French medical database system (PMSI), over the period from 2013 to 2019. French ICUs admitted a total of 4055 adult patients with PCP. Among all hospitalized PCP cases, the proportion requiring ICU admission increased from 17.8 in 2014 to 21.3% in 2019 (P < 0.001). The incidence of severe PCP rose from 0.85 in 2013 to 1.32/100,000 adult inhabitants in 2019 (P < 0.0001), primarily due to the proportion of HIV-negative patients that increased from 60.6% to 74.4% (P < 0.0001). Meanwhile, the annual number of severe PCP cases among patients with HIV infection remained stable over the years. In-hospital mortality of severe PCP cases was 28.5% in patients with HIV infection and 49.7% in patients without. Multivariable logistic analysis showed that patients with HIV infection had a lower adjusted risk of death than patients without HIV infection (Odds Ratio [OR]: 0.30, 95% confidence interval [95CI]: 0.17-0.55). Comorbidities or conditions strongly associated with hospital mortality included the patient's age, Simplified Acute Physiologic Score II, congestive heart failure, coagulopathy, solid organ cancer, and cirrhosis. A vast array of autoimmune inflammatory diseases affected 19.9% of HIV-negative patients. The number of PCP cases requiring ICU admission in France has risen sharply. While the yearly count of severe PCP cases in HIV-infected patients has remained steady, this rise predominantly affects cancer patients, with a recent surge observed in patients with autoimmune inflammatory diseases, affecting one in five individuals.

Characteristics of recurrence in area postrema-onset NMO spectrum disorder - a retrospective cohort study

BackgroundNeuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory autoimmune disease with high risk of recurrence and disability, the treatment goal is a recurrence free state. Area postrema (AP) is one of the most common involved area of NMOSD, which may have a particular significance in the pathogenesis of NMOSD and clinical heterogeneity. Our study is to investigate the clinical and recurrent characteristics AP onset NMOSD patients.MethodsA retrospective study was done in a cohort of 166 AQP4-IgG seropositive NMOSD patients which were identified by the 2015 IPND criteria. The patients were divided into AP onset (APO-NMOSD) group and non-AP onset (NAPO-NMOSD) group based on the initial episode location. Clinical features and recurrence differences of two groups were compared.ResultsThe APO-NMOSD group and NAPO-NMOSD group had a population ratio of 24:142. APO-NMOSD patients were younger (34.6y VS 42.3y, P = 0.013), had lower EDSS at first episode (0.7 VS 4.2, p = 0.028) and last follow up (1.9 VS 3.3, p = 0.001), more likely to have multi-core lesions at the first attack (33.3% VS 9.2%, P = 0.001). Also, they had a higher annual recurrence rate (0.4 ± 0.28 VS 0.19 ± 0.25, P = 0.012). In natural course NMOSD patients without immunotherapy, APO-NMSOD had a shorter time of first relapse (P < 0.001) and higher annual recurrence rate (0.31 ± 0.22 VS 0.16 ± 0.26, P = 0.038) than NAPO-NMOSD. APO-NMOSD group also have a higher risk of having the first relapsing compared to optic neuritis onset-NMOSD (HR 2.641, 95% CI 1.427–4.887, p = 0.002) and myelitis onset-NMOSD group (HR 3.593, 95% CI 1.736–7.438, p = 0.001). Compared to NAPO-NMOSD, APO-NMOSD has a higher likelihood of brainstem recurrence (28.6% vs. 4.7%, p<0.001) during the first recurrence, while NAPO-NMOSD is more susceptible to optic nerve involvement (10.7% vs. 41.1%, p = 0.01).ConclusionAQP4-IgG seropositive NMOSD patients with AP onset are youngers and have higher risk of recurrence. Clinicians should pay attention to AP damage in NMOSD, as it indicates a potential risk of recurrence.Trial registrationRetrospectively registered.

Low T3 syndrome is associated with the severity of myelin oligodendrocyte glycoprotein antibody-associated disease exacerbation.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune inflammatory disease of the central nervous system, (CNS) different from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). While numerous studies have delved into the involvement of thyroid antibodies (ATAbs) and thyroid function in NMOSD and MS. The objective of this study is to explore the clinical significance of thyroid dysfunction and ATAbs abnormalities in adult patients with MOGAD. 36 adult inpatients diagnosed with MOGAD and 47 sex- and age-matched healthy controls were enrolled. Patients were divided into two groups based on the presence or absence of low T3 syndrome. Demographics, clinical characteristics, and results of auxiliary examinations were compared across the subgroups. Moreover, an analysis was conducted to explore the correlations between thyroid hormone levels and Expanded Disability Status Scale (EDSS) scores. Thyroid dysfunction was notably more frequent in MOGAD patients than healthy controls (p < 0.0001), particularly low T3 syndrome (p=0.03). Furthermore, subgroup analyses revealed that the low T3 syndrome group exhibited higher EDSS scores and a higher proportion of individuals with EDSS scores > 3, in comparison to the non-low T3 syndrome group (p = 0.014, p = 0.046). However, no significant differences were observed in demographic characteristics, annual relapse rates, clinical phenotypes, laboratory and MRI results, and EEG abnormalities between the two groups. Additional Spearman's analysis showed significantly negative correlations between the TT3 and FT3 levels with EDSS scores (r = -0.367, p = 0.028; r = -0.377, p = 0.024). Typical brain lesions and paralateral ventricle lesions were significantly rare in patients with positive ATAbs compared to those with negative ATAbs (p = 0.0001, p = 0.03), although the incidence of ATAbs abnormalities did not differ significantly between MOGAD patients and healthy controls. Overall, this study confirmed thyroid dysfunction, especially low T3 syndrome, is frequent in adult MOGAD patients. Patients with low T3 syndrome exhibited elevated EDSS scores and a significantly higher incidence of unfavorable condition. additionally, the correlation analysis model manifests that FT3 and TT3 levels were negatively correlated with EDSS scores. These evidences indicate that low T3 syndrome is associated with the severity of MOGAD exacerbation.

Cellular immune response to the anti-SARS-CoV-2 BNT162b2 mRNA vaccine in pediatric autoimmune inflammatory rheumatic disease patients and controls.

This paper aims to compare the cellular immune response to the SARS-CoV-2 BNT162b2 vaccine of pediatric patients with autoimmune inflammatory rheumatic disease (pAIIRD) and healthy controls. A prospective longitudinal study was conducted between April 2021 and December 2022 at the Tel Aviv Medical Center. Children <18 years, with pediatric-onset AIIRD and healthy controls, who have received at least two doses of the BNT162b2 vaccine, were included. Humoral response was evaluated by serum levels of anti-SARS-CoV-2 receptor-binding domain antibodies. Cellular response was evaluated by flow cytometry, measuring IFNγ and TNFα production by CD4+ T cells following stimulation with SARS-CoV-2 Spike peptide mix. The study included 20 pAIIRD patients and 11 controls. The mean age of participants was 12.6 ± 2.94 years, with 58.1% females. The cellular response to the BNT162b2 vaccine was statistically similar in both groups. However, the humoral response was statistically lower in pAIIRD compared with the healthy control group. There was no statistically significant correlation between the humoral response and cellular response. During the study period, 43.75% of AIIRD children and 72.7% of controls had a breakthrough COVID-19 infection (P = 0.48). Bivariate models examining the effect of the cellular response and presence of an AIIRD on breakthrough infections found no effect. Compared with healthy controls, pAIIRD demonstrated similar cellular responses. Patients showed reduced humoral response compared with healthy adolescents, but similar breakthrough infection rates. These findings may support the importance of the cellular response in protecting against COVID-19 infections.

CORTICOSTEROID-INDUCED EXPRESSION OF MICROBIAL VIRULENCE CAN ENHANCE THE DEVELOPMENT OF HOST INFECTIOUS DISEASE

Corticosteroids regulate a number of physiological processes and are synthetic analogs of the natural steroid hormones produced by the adrenal cortex. As drugs, corticosteroids are non-inflammatory and are used for the treatment of plethora of conditions which include arthritis, kidney, skin, lungs or thyroid disorders, for the treatment and relief of symptoms of allergies and symptoms of some gastrointestinal disorders. In addition, glucocorticoids can regulate the effects of inflammatory disorders, including sepsis, autoimmune diseases, and allergies. These conditions are potentially fatal. Consequently, this drug class is among the most commonly prescribed globally. One representative of corticosteroid class of drugs is dexamethasone which is used to treat allergies, adrenal problems, arthritis, asthma, diseases of blood or bone marrow, inflammation, kidney diseases, different types of skin conditions, and episodes of multiple sclerosis. Virulence factors help bacteria colonize the host at the level of the cell. In their nature, these factors are secretory, associated with the membrane or present in the cytosol. Secretory factors allow bacterium to circumvent the host immune response, while membrane factors aid bacterium in adhesion to the host cell. Finally, cytosol factors help bacteria adapt metabolically, physiologically, and morphologically to their changing environment. One such factor is aspartyl proteinase, a protein that degrades other proteins and is a virulence factor in many pathogens playing a role in the host invasion process. Another important virulence factor is the ability to form biofilms, which can render bacteria resistant to antimicrobials. Despite the widespread use of corticosteroids, including dexamethasone, little is known about their possible influence on the expression of virulence factors such as aspartyl proteinase. If such a connection is to exist the use of corticosteroids could elicit pathogenesis in certain microbes. In the here-presented study we wanted to investigate the effects of dexamethasone on the growth, expression of aspartyl proteinase and biofilm formation in three E. coli strains that were previously isolated from patients suffering from urinary tract infection. To this aim, we amended the growth media with 0.5 mg/mL dexamethasone. Bacterial growth was measured over the period of 24 hours and the effect of dexamethasone was established at different time points. Administration of 0.5 mg/mL glucocorticoid drug dexamethasone did not significantly affect bacterial growth. However, it resulted in an increase in concentration of secreted E. coli virulence factor aspartyl proteinase, which increased up to 2.6-fold for some E. coli strains. In addition, we noted the increased biofilm formation in to three out of four studied strains. This study indicates dexamethasone as a possible trigger molecule for the expression of virulence factor aspartyl proteinase in E. coli.

Prevalence and Associated Factors of Chronic Kidney Disease in Rheumatoid Arthritis Patients at Ratchaburi Hospital, Thailand

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, common in Thailand. The prevalence of chronic kidney disease (CKD) in Thai RA patients is uncertain. Objective: To study the prevalence and associated factors of CKD in RA patients. Materials and Methods: A retrospective study based on medical records was conducted. Participants were RA patients who visited Ratchaburi Hospital between May 2022 and October 2022. CKD was defined according to an eGFR below 60 mL/minute/1.73 m² by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The prevalence of CKD and associated factors was determined. Logistic regression was used to analyze the data. Results: The present study included three hundred and two patients with a mean (SD) age of 53.7 (±12.1) years. Median (IQR) RA disease duration was 60.0 (97.7) months. The prevalence of CKD was 19.2%, consisting of 13.2% at stage 3a, 4.0% at stage 3b, 2.0% at stage 4, and 0% at stage 5. The factors associated with CKD were age of 60 years or older, hypertension, dyslipidemia, age of RA onset of 60 years or older, more than three months of joint pain before disease-modifying antirheumatic drugs (DMARDs) treatment, higher erythrocyte sedimentation rate (ESR) and RA treatment without methotrexate (p&lt;0.05). The findings from the multivariate analysis of factors associated with CKD revealed that hypertension (adjusted OR 2.84, 95% CI 1.36 to 5.90), more than three months of joint pain before DMARDs treatment (adjusted OR 56.70, 95% CI 12.64 to 254.41), higher ESR (adjusted OR 1.01, 95% CI 1.01 to 1.03), and RA treatment without methotrexate (adjusted OR 5.45, 95% CI 1.87 to 15.89) were associated with CKD after adjusting for age. Conclusion: The prevalence of CKD in RA patients was higher than in normal population. Factors associated with CKD were hypertension, more than three months of joint pain before DMARDs use, and higher ESR and RA treatment without methotrexate. Results from the present study should be applied to the management plans for patients with RA.

Serum IL-23, IL-17 and TNF-α level as Psoriasis severity markers: A hospital based cross sectional study.

Serum IL-23, IL-17 and TNF-α level as Psoriasis severity markers: A hospital based cross sectional study.