BMC Immunology最新文献

Introduction: Adalimumab is a monoclonal antibody that is used to treat autoimmune and inflammatory diseases. Biosimilars for adalimumab, including Hyrimoz, have been developed. We aimed to evaluate the effectiveness and adverse effects of Hyrimoz after switching.

Methods: The cohort consisted of patients treated with adalimumab at the Clinical Immunology Outpatient Department of the Erasmus Medical Center between February 2021 and February 2023. Data were collected through electronic patient files and questionnaires sent to the patients. The primary outcome was the number of flares after switching to Hyrimoz, compared to a similar period before the switch. The secondary outcomes were reported adverse effects and patient experience using Hyrimoz.

Results: A total of 185 patients were eligible for inclusion. There was no significant difference in the occurrence of flares between Humira and Hyrimoz (P = 0.456). Forty-six of the 185 patients reported adverse effects (24.9%). A total of 25/185 (13.5%) patients reported pain during injection, which was the most frequently reported adverse effect. During the course of this study, 60/185 (32.4%) patients discontinued Hyrimoz treatment because of flares (n = 17 [9.2%]), adverse effects (n = 27 [14.6%]), or more subjective complaints (n = 15 [8.1%]) related to the underlying disease. One patient discontinued treatment because of inactive disease.

Conclusion: The number of flares before and after switching to Hyrimoz was comparable. However, adverse effects and increased subjective complaints have been reported after switching to this new biosimilar.

Background: Having psoriasis in hard-to-treat areas, such as the scalp, face, palms, soles, nails, and genitals, can suffer from a reduced quality of life. This study was designed to investigate the prevalence and risk factors of hard-to-treat body locations of psoriasis, and to describe patients' clinical and demographic characteristics, and quality of life impacts.

Methods: We conducted a multicenter observational epidemiological study involving over 1000 hospitals in China, enrolling a total of 7032 psoriasis patients. Groups were compared to patients without involvement of hard-to-treat areas.

Results: The most frequently affected hard-to-treat area was the scalp (60.01%), followed by the face (22.47%), nails (18.87%), palms or soles (18.23%), genitals or vulvas (12.00%), respectively. Among all patients, 70.71%, 36.65%, 16.30%, 6.48% and 1.45% of patients had involvement of ≥ 1, ≥2, ≥ 3, ≥4 or ≥ 5 hard-to-treat areas. There was a male predominance among patients with involvement of at least one hard-to-treat area(P < 0.001). The smoking rate, BMI (body mass index) and psoriasis family history in patients with at least one hard-to-treat area involvement were significantly higher than those in patients without hard-to-treat area involvement (P < 0.001), especially among patients with nail involvement. With regards to current DLQI (dermatology life quality index), satisfactory rate, and current BSA (body surface area), these findings were all significantly different (P < 0.001) when compared to patients without involvement of a hard-to-treat area. Notably, even in mild-to-moderate psoriasis (BSA < 10), 65.10% of patients showed involvement of ≥ 1 hard-to-treat area, with significant impacts on quality of life (DLQI increase, all P < 0.001) and treatment satisfaction (P < 0.001 vs. non-involved).

Conclusion: Psoriasis commonly affects hard-to-treat locations, even in patients with mild to moderate disease (BSA < 10). The disproportionate impact on quality of life (particularly genital/face involvement) and treatment satisfaction underscores the need for: (1) routine assessment of these areas regardless of BSA, and (2) targeted management of modifiable risk factors (smoking, obesity). These findings support incorporating hard-to-treat area evaluation into psoriasis severity assessments and treatment algorithms.

Brucella is a common kind of bacteria that has the ability to live within cells and may cause diseases that can be transmitted between animals and humans. Current medical therapy struggles to effectively eradicate Brucella. Thus, it is necessary to develop a multi-epitope vaccine (MEV) in order to effectively prevent Brucella infection. To achieve this objective, we used the reverse vaccinology methodology based on omp19 and Bacterial surface antigen (D15). After conducting our research, we successfully identified 2 cytotoxic T lymphocyte (CTL) epitopes, 2 helper T lymphocyte (HTL) epitopes, and 2 linear B cell epitopes from Omp19 and Bacterial surface antigen (D15). These epitopes will be further examined in our study. In order to maintain the proper folding of the protein, we connected GGGS and EAAAK consecutively. Adjuvants are added to the N-terminal of the vaccine peptide to boost its immunogenicity. In order to assess the immunity, stability, protection, and practicality of the final MEV, a construct consisting of 387 amino acids was created by connecting linkers and adjuvants. Furthermore, molecular docking and simulations using molecular dynamics were conducted to confirm the binding strength and durability of the MEV-TLR5. Subsequently, codon adaptation and in silico cloning analyses were conducted to determine the potential codons for expressing the MEV. The findings indicated that the MEV exhibited a significant level of immunogenicity. This work has collectively established a theoretical foundation for the development of a vaccine against Brucella.

Background: Inflammatory bowel disease (IBD) management remains challenging due to limited preventive strategies and the low bioavailability of therapeutic agents like resveratrol (RSV). While RSV exhibits anti-inflammatory properties, its preventive potential via gut microbiome modulation remains unexplored.

Methods: A murine colitis model was established using 2.5% DSS, with mice randomized into control (CON), DSS, therapeutic RSV treatment (RSV), and preventive RSV treatment (PRE) groups. Clinical outcomes, intestinal barrier integrity, inflammatory cytokines, macrophage polarization, TLR4/NF-κB signaling, and gut microbiota (16S rRNA sequencing) were systematically evaluated.

Results: Preventive RSV (PRE) outperformed therapeutic RSV across all metrics. PRE attenuated colitis severity by 51.4% (weight loss, P < 0.001 vs. RSV) and restored mucosal architecture (P = 0.048 vs. DSS). Mechanistically, PRE normalized barrier function via transcriptional (ZO-1: 56.7% of CON; Occludin: 14-fold induction vs. DSS) and protein-level recovery (ZO-1: 96.5% of CON, P = 0.02), suppressed pro-inflammatory cytokines (TNF-α: 80.8%; IL-6: 69.9%; IL-18: >96%, P < 0.001 vs. DSS), and promoted M2 macrophage polarization (CD206: 1.7-fold vs. CON, P = 0.02) through TLR4/NF-κB inhibition (53% TLR4 reduction vs. 15% with RSV, P < 0.001). Despite comparable α-diversity between RSV and PRE, PRE uniquely enriched barrier-protective taxa (Lactococcus, Muribaculum) and restored microbial amino acid biosynthesis. Crucially, PRE's efficacy despite low systemic bioavailability implicated microbiome-mediated "luminal priming" as its primary mechanism.

Conclusions: This study redefines preventive RSV as a microbial ecosystem engineer that preemptively fortifies the gut against inflammation via microbiome-immune-metabolic crosstalk. By prioritizing ecological prevention over symptom suppression, our findings offer a transformative "food as medicine" strategy for IBD, highlighting RSV's potential as a chronotherapeutic agent to reshape clinical paradigms.

Background and objectives: The identification of affordable and easily accessible indicators to predict overall survival is important for tumor immunotherapy. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells, which promote tumor immune escape in the tumor microenvironment (TME). This study aimed to determine whether peripheral blood MDSCs could determine their potential as predictors of survival in tumor patients with immunotherapy.

Methods: Flow cytometry was used to detect peripheral blood monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic myeloid-derived suppressor cells (G-MDSCs) in 126 patients. Multivariate Cox regression analysis was conducted to examine the associations between peripheral blood MDSCs and patient survival. The receiver operating characteristic (ROC) curve determined the optimal cutoff value for peripheral blood MDSCs and grouped the indicators. The relationship between peripheral blood M-MDSCs and the prognosis and treatment outcome of tumor patients was explored.

Results: The proportion of peripheral blood M-MDSCs was associated with the prognosis of patients with tumors, as were tumor metastasis, the red blood cell count, absolute neutrophil count, absolute monocyte count, and BMI. Multivariate Cox regression analysis revealed that M-MDSCs, absolute lymphocyte value, and tumor metastasis were independent risk factors affecting the prognosis of patients with tumors. Detection of peripheral blood M-MDSCs obtained high sensitivity and specificity for tumor diagnosis. Patients with high M-MDSCs percentage demonstrated reduced survival durations and diminished responses to immunotherapy compared to those with low M-MDSCs percentage.

Conclusions: Peripheral blood M-MDSCs may be used to predict overall survival and immunotherapy efficacy outcomes. This study provides a putative predictive biomarker for clinicians to choose from to predict tumor patients' survival and the selection of receiving immunotherapy regimens.

Background: The human leukocyte antigen (HLA)-B27 gene is highly associated with ankylosing spondylitis (AS). However, not everyone who carries the HLA-B27 antigen develops AS, indicating that factors beyond the HLA-B27 gene contribute to the disease's onset. AS is an autoimmune disease in which co-stimulatory systems have been widely explored. Therefore, we aimed to analyze the association between single-nucleotide polymorphisms (SNPs) in co-stimulatory/inhibitory molecules and AS to identify other key factors involved in developing the disease.

Results: This study recruited 32 patients with AS and 32 controls. DNA was extracted from whole blood, and PCR amplification was performed to target the promoter regions of the CTLA4, CD28, and PDCD1 genes. Chi-square and Fisher's exact tests were used under various genetic models to assess differences in genotype and allele distribution between cases and controls. The results showed that rs201801072 of the CD28 gene (TT + CT vs. CC, p = 0.001) and rs11571319 of the CTLA4 gene were associated with AS (GG vs. AG + AA, p = 0.001). Logistic regression analysis showed that rs201801072 (CD28) and rs11571319 (CTLA4) were independently associated with AS. A significant positive interaction was observed between these SNPs and HLA-B27 positivity, further increasing the risk of AS (T-allele: OR = 6.15; G-allele: OR = 13.30, both p < 0.001). HLA-B27 carriers exhibited an extremely high risk of AS (OR = 65.0, p = 1.19E-06).

Conclusions: The elevated frequencies of specific alleles in AS patients compared to controls highlight the potential involvement of these SNPs as key factors in the pathogenesis of AS, offering new insights into the genetic mechanisms underlying the disease.

Background: Primary immunodeficiencies (PIDs) are a group of diseases that develop as a result of primary or congenital malfunction of the immune system and progress with chronic and/or recurrent bacterial, fungal, protozoal and/or viral infections. In this study, we aimed to examine the effects of the COVID-19 pandemic on depression, anxiety levels and psychological resilience in patients with PID and to compare them with those in controls.

Methods: Seventy patients, aged 18-65 years, who were being followed up with a diagnosis of PID and 69 people as healthy control group, participated in our study. The participants were evaluated cross-sectionally once; sociodemographic data form, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Resilience Scale for Adults (RSA), and COVID-19 Evaluation form were administered to the participants.

Results: HAM-A and HAM-D scores were significantly higher in PID patients compared to controls (HAM-D: 5.5 vs. 3.0, p < 0.001; HAM-A: 6.0 vs. 4.0, p = 0.008). RSA was significantly lower in the patient group (RSA total: 122.5 vs. 136.0, p < 0.001), and pandemic-related risk perception was higher (PRPS: 33.9 vs. 28.3, p < 0.001). Sleep, appetite, and attention-related disturbances were also more common in the patient group. Multivariate regression analyses revealed that PID diagnosis was an independent predictor of increased depression severity (HAM-D), lower psychological resilience (RSA), and greater pandemic-related risk perception. Female sex was independently associated with higher anxiety severity (HAM-A). A personal psychiatric history and greater number of comorbidities were also significant predictors of psychological vulnerability, particularly in relation to depression and anxiety.

Conclusion: Given the observed associations between PID and increased levels of depression, anxiety, and reduced psychological resilience during the pandemic, clinicians may consider heightened vigilance for psychological symptoms in this population during times of public health crisis.

Objective: The purpose of this study was to investigate the predictive relevance of CD27 and CD117 expression and the prognostic value in newly diagnosed multiple myeloma (NDMM) patients.

Methods: This retrospective cohort study analyzed 160 newly diagnosed multiple myeloma (NDMM) patients at Beijing Chaoyang Hospital (2016-2023), evaluating CD27 (TNF receptor family member regulating plasma cell differentiation) and CD117 (c-KIT proto-oncogene product mediating hematopoietic cell survival) expression patterns via pretreatment flow cytometry. Patients were stratified by CD27/CD117 membrane positivity to assess their combined prognostic significance on disease progression, with survival outcomes tracked through standardized clinical surveillance protocols.

Results: The CD27 negative cohort demonstrated severe disease burden, evidenced by elevated β2-MG, increased bone marrow plasma cell infiltration, reduced hemoglobin levels, percentage of high ISS III. Kaplan-Meier analysis demonstrated that CD27 positive cohort showing significantly prolonged median PFS versus CD27 negative counterparts (78 vs. 33 months, P = 0.0078). While CD117 alone lacked prognostic significance, combined CD27(+)CD117(+) status was associated with superior PFS (P = 0.0041 vs. subgroups), earlier ISSMASS staging (P = 0.005, P = 0.021), deeper therapeutic remission rates(Protease inhibitor-based therapy, P = 0.009), and lower frequency of high-risk cytogenetic abnormalities compared to all other combinations, and particularly outperforming CD27(-)CD117(-) patients. Among CD27-expressing patients, CD117 positive patients had better survival performance (P = 0.0424). Multivariate Cox regression confirmed CD27 positivity as an independent protective factor (HR 0.50, P = 0.009) and thrombocytopenia (PLT < 150 × 10⁹/L) as a risk predictor (HR 2.28, P = 0.002), both maintaining significance after adjusting for conventional parameters.

Conclusion: CD27 positive patients have a better prognosis, and the combination of CD27 and CD117 allows refined prognostic risk stratification of MM patients. The expression of CD27 and CD117 is associated with improved prognosis.

Background: Alpha gal syndrome (AGS) is a delayed allergy to red meat, due to IgE to galactose-alpha-1,3-galactose (alpha-gal). Sensitization occurs via tick bites. It has been described in the US, Europe, Australia, Japan and South Korea, but reports from the Indian subcontinent are rare. We report the demographics of alpha-gal allergy for the first time from the Indian subcontinent and possible association with vaccine allergy.

Methods: Patients diagnosed with alpha-gal syndrome (AGS) from 2018 to 2024 were selected in this study. AGS was identified by the occurrence of allergic symptoms up to 8 h of ingestion of red meat, with positive serum IgE to alpha-gal > IgE to red meat, and negative IgE to BSA. Allergy to vaccines containing bovine products were also identified in patients with AGS.

Results: Fifty-seven patients were identified. Thirty-one (54.3%) were 12 years or younger. There were more females among adults (63.2%) compared to children (50.0%), though statistically not significant. There was no difference between children and adults in relation to clinical features and time of onset of symptoms. However, 5/6 of adults with severe anaphylaxis (grade 5) were females. Six patients with AGS developed allergy, including anaphylaxis, to the measles, mumps, rubella (MMR, n = 3), rubella (n = 1), varicella (n = 1) and anti-rabies (n = 1) vaccines.

Conclusion: AGS is an important cause of food and vaccine allergy in the Indian subcontinent and is commoner in children unlike in other regions. However, the clinical features are similar to adults.