BMC Immunology最新文献

Background and aims: Common variable immunodeficiency (CVID) represents the most frequently diagnosed symptomatic primary immunodeficiency (PID), marked by a heterogeneous presentation involving infectious and non-infectious symptoms. This study investigated the association between serum copeptin levels and right ventricular functions (RVF) and pulmonary complications in patients diagnosed with CVID.

Methods: The study analyzed data from 60 individuals with a confirmed diagnosis of CVID and 30 age- and sex-matched healthy volunteers (HVs). Clinical and biochemical parameters were sourced from existing hospital records.CVID patients were categorized into two subgroups: those with and without pulmonary complications. Comparisons of serum copeptin levels were made between these groups and between the overall CVID cohort and healthy controls. RVF was evaluated using tricuspid annular plane systolic excursion (TAPSE) and supplementary echocardiographic indicators.

Results: The CVID group had a median age of 40 years (interquartile range [IQR]: 30-55), with 51.7% being male, while the HVs group had a median age of 37 years (IQR: 28-47.5), with 60% male. No significant differences in age (p = 0.226) or sex distribution (p = 0.45) were observed between the groups. CVID with pulmonary complications (CVID-P) exhibited significantly elevated copeptin levels compared to those without such complications (p < 0.001). According to ROC analysis, a copeptin cut-off value of 11 pmol/L significantly differentiated patients with CVID-P from those without pulmonary complications (p < 0.001). Moreover, overall copeptin levels were significantly higher in the CVID group than in HVs (p < 0.001). A copeptin cut-off value of 21 pmol/L effectively distinguished CVID patients with low TAPSE from those with normal TAPSE values (p < 0.001). Pulmonary complications and low TAPSE were independently associated with increased copeptin levels (p = 0.006 and p = 0.004, respectively).

Conclusion: The development of pulmonary complications and RV dysfunction were associated with elevated serum copeptin levels in CVID. Measuring serum copeptin concentration may be a useful biomarker in diagnosing and prognosis pulmonary diseases and RV dysfunction in CVID.

Background: X-linked retinoschisis is a retinovitreal disorder primarily affecting males, starting in childhood. Over time, patients experience deterioration of vision due to the lack of retinoschisin-1 function. In clinical trials performing intravitreal gene delivery in those affected by this disorder, ocular inflammation was observed, which may have masked efficacy. A subsequent study focusing on analyzing the populations of peripheral blood mononuclear cells and cytokines in adults with this disease reported aberrant dendritic cell numbers and cytokine levels in peripheral blood, indicating that adults with this disease may have an altered baseline immunity. Whether the aberrant peripheral immunity in affected adults was a consequence of advanced eye pathology remained unclear. This study focuses on analyzing the populations of blood lymphocyte subsets in children aged 0 to 7 years with X-linked retinoschisis and age-matched controls using flow cytometry.

Results: The fractions of lymphocyte subsets that were CD16a+/CD56+, namely natural killer cells, were significantly lower in blood samples from children with X-linked retinoschisis. In children with X-linked retinoschisis, the fractions of CD3+/CD4 + T cells were higher, and the fractions of CD3 + CD8 + T cells were lower, despite having the same amounts of total CD3 + T cells within their lymphocyte populations. This resulted in a significantly greater CD4/CD8 ratio in children with X-linked retinoschisis compared to age-matched controls.

Conclusions: Alterations were found in blood lymphocyte compositions of children with X-linked retinoschisis within both innate and adaptive immune axes. Some alterations including an elevation of CD4/CD8 ratio in X-linked retinoschisis mirror those previously found in adult patients with this disease. The fact that these abnormalities were present early in this disease indicates that retinoschisin-1 may play a role in regulating immunity in addition to retinal structure. The findings may have implications for future treatments such as ocular gene delivery.

This study systematically reviews the literature to explore the potential causes of anti-sperm antibody (ASA) production among infertile men. A comprehensive search of PubMed was conducted in December 2024, utilizing keywords such as "anti-sperm antibody," "immunologic infertility," and related terms. The search yielded 2215 studies, which were screened by title and abstract, excluding 1857 studies. A total of 358 full-text articles were assessed for eligibility, and finally, 51 studies were included. Twenty-three thousand one hundred eight patients were involved in the included studies; 22,702 patients were infertile, and 406 were fertile controls. Infectious disease were the most commonly investigated causes of ASA production including chlamydia trachomatis infection with 9 studies. History of vasectomy and vasectomy reversal with 9 studies, varicocele (7), cryptorchidism (5), Inguinal hernia repair and other genital or inguinal surgeries (5), HPV infection (4), and seminal bacterial community and culture (4) were other potential investigated causes. Adeno-associated virus, mumps, congenital absence of vasa, testicular microlithiasis, testicular sperm extraction, testicular torsion, and testicular trauma were other causes that their correlation with ASA was explored. Vasectomy emerged as the most frequently studied factor significantly correlated with ASA production. Other conditions, like psychogenic anejaculation, prostatitis, and Buerger's disease, were also associated, though findings on some factors remain controversial. This study highlights the diverse potential causes of ASA production in infertile males, categorized into infectious, autoimmune, inflammatory, and anatomical conditions. However, the variability in results underscores the need for further research with larger populations to clarify the underlying causes of ASA production in male infertility.

Introduction: Antivimentin/cardiolipin antibodies (aVim/CL) have emerged as potential diagnostic markers for antiphospholipid syndrome, However, their association with pregnancy outcomes remains unclear. This study explores the clinical significance of aVim/CL in pregnancy loss.

Methods: A retrospective analysis was conducted on 429 pregnant women with at least one spontaneous miscarriage at The Third Affiliated Hospital of Wenzhou Medical University (October 2019- August 2022). Multivariable logistic regression and stratified analyses were utilized to assess the relationship between aVim/CL levels and pregnancy loss.

Results: Among the 429 participants, 79 experienced pregnancy loss, while 350 had live births. Elevated aVim/CL levels were associated with an increased risk of pregnancy loss, with an odds ratio (OR) of 1.108 (95% CI, 1.037-1.185). The area under the ROC curve (AUC) was 62.8, with a sensitivity of 77.2% and a specificity of 44%. A nonlinear L-shaped relationship was identified, with a threshold of 6.86 ng/mL, below which the risk of pregnancy loss significantly increased. No correlations were found between aVim/CL and coagulation or immune biomarkers.

Discussion: Elevated aVim/CL levels were identified as independent predictors of pregnancy loss in women with a history of spontaneous miscarriage. The threshold of 6.86 ng/mL may provide valuable clinical insights for risk stratification.

Objective: The aim of this study was to evaluate the diagnostic value of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels in multiple sclerosis (MS) and optic neuromyelitis optica spectrum disorders (NMOSD) and their relationship with disease prognosis by Meta-analysis, and to explore their potentials in early diagnosis of the disease and monitoring of its course.

Methods: We systematically searched China National Knowledge Infrastructure (CNKI), VIP database, Wanfang database, PubMed, Wiley online library, and web of science databases for relevant literature on GFAP in neuroimmune diseases, and the time limit for searching was from inception to December 1, 2024, and two evaluators independently assessed all the studies. Two evaluators independently assessed the quality of all the studies, evaluated the data in detail according to the criteria of risk of bias, and performed Meta-analysis using RevMan 5.4.1 software and STATA 18.

Results: Through literature screening, 12 studies were finally included, involving a total of 1731 participants, of which 871 were in the control group and 869 were in the experimental group. Meta-analysis results showed that GFAP levels in MS patients were significantly higher than those in healthy control groups [MD = 0.98, 95% CI (0.70, 1.25), P < 0.0001]; NfL levels were also significantly higher than controls [MD = 0.76, 95% CI (0.06, 1.46), P = 0.03]. In patients with optic neuromyelitis optica spectrum disease (NMOSD), GFAP levels were significantly higher than controls [MD = 0.97, 95% CI (0.03, 1.91), P = 0.04]; NfL levels were also significantly higher than controls [MD = 0.24, 95% CI (0.02, 0.46), P = 0.03]. Analysis of different disease stages showed that compared with healthy controls, GFAP levels were significantly elevated in patients with MS in the deteriorating phase [MD = 2.38, 95% CI (1.40, 3.37), P < 0.0001], in the active phase [MD = 2.01, 95% CI 0.20, 3.82), P = 0.03], and in the remission phase at a lower level of elevated GFAP levels [MD = 1.33, 95% CI (0.20, 2.46), P = 0.02]. For GFAP survival analysis in MS patients, the results showed no statistical significance [HR = 1.78, 95% CI (0.47, 6.66), P = 0.39].

Conclusion: The levels of GFAP and NfL in MS and NMOSD patients were significantly higher than those in healthy controls. GFAP levels demonstrate a progressive decline correlating with MS disease activity-from exacerbation through active to remission phases-yet remain persistently elevated compared to controls. These findings indicate its potential utility for MS diagnosis and disease monitoring.

Background: Complete complement factor I (CFI) deficiency is an inborn error of immunity (IEI) that results in heightened susceptibility to infections and immune dysregulatory disorders. This systematic review seeks to enhance our understanding of the clinical characteristics, genotype-phenotype correlations, and treatment outcomes in patients with complete CFI deficiency, including three novel cases. We conducted a comprehensive literature review of cases published from 1996 to November 2024, identifying 49 patients with homozygous or compound heterozygous mutations in the CFI gene.

Results: Among the 49 patients, the mean age at initial presentation was 7.19 (± SD: 9.75) years. Most patients presented with infectious manifestations (n: 37, 75.5%), particularly sepsis (n: 18, 36.7%). The predominant pathogens were encapsulated organisms, particularly Neisseria meningitidis. Immune dysregulatory manifestations involved rheumatologic (n: 14, 28.57%), neurologic (n: 11, 22.4%), and renal (n: 8, 16.3%) disorders. Immunological evaluations showed low or absent levels of C3 and CFI in most patients. Genetic analysis identified 45 distinct mutations; less deleterious mutations, such as missense and splicing variants, were more common in those with immune dysregulation. Notably, three patients treated with eculizumab demonstrated significant clinical improvement.

Conclusion: Complete CFI deficiency presents a varied clinical spectrum, from asymptomatic to recurrent infections and immune dysregulation. Early diagnosis and targeted therapies, such as eculizumab, may improve patient outcomes. These findings underscore the necessity for further research into the nature of complete CFI deficiency and the development of optimal management strategies.

Objective: To examine whether pidotimod affects the progression and severity of experimental autoimmune encephalomyelitis (EAE), a classic animal model of multiple sclerosis (MS), the balance of splenic lymphocytes in pidotimod-treated and untreated EAE mice was examined.

Methods: C57BL/6J mice were immunized by subcutaneous injection of an emulsion containing MOG35-55, with subsequent monitoring of their general condition and clinical scores following treatment with pidotimod or saline solution (vehicle control). Hematoxylin and eosin (H&E) staining, along with flow cytometry (FCM), was employed to evaluate leukocyte infiltration, while FluoroMyelin™ Green staining was utilized to assess axonal demyelination in the central nervous system (CNS). Additionally, FCM was conducted to investigate the effects of pidotimod on splenic lymphocytes both in vitro and in vivo during the peak stage of EAE.

Results: Compared to the vehicle control, pidotimod treatment significantly reduced the clinical scores, decreased leukocyte infiltration in the spinal cord and brain, and suppressed demyelination in the spinal cord. Furthermore, pidotimod treatment markedly increased the populations of CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells (Tregs) and CD8⁺ Foxp3⁺ Tregs, while decreasing the numbers of CD4⁺ IFN-γ⁺ helper T cells (Th1), CD4⁺ IL-17⁺ helper T cells (Th17), and CD8⁺ IL-17⁺ cytotoxic T cells (Tc17) in the spleen during the peak stage of EAE both in vitro and in vivo. Additionally, pidotimod treatment significantly diminished the population of B220⁺ TNF-α⁺ B cells in the spleen at the peak stage of EAE both in vitro and in vivo.

Conclusions: The present study preliminarily explored the effects and potential immunomodulator mechanisms of pidotimod in treating EAE mice. Results indicated that pidotimod treatment decreased the percentages of CD4⁺ IFN-γ⁺ Th1 cells, CD4⁺ IL-17⁺ Th17 cells, CD8⁺ IL-17⁺ Tc17 cells and B220⁺ TNF-α⁺ B cells, while increasing the percentages of CD4⁺ CD25⁺ Foxp3⁺ Tregs and CD8⁺ Foxp3⁺ Tregs in the spleen at the peak stage of EAE. Additionally, pidotimod reduced leukocyte infiltration into the spinal cord and brain, as well as demyelination in the spinal cord. These findings suggest that the neuroprotective effects of pidotimod in EAE mice may be its ability to regulate the balance of splenic lymphocytes.

Background: Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare inborn error of immunity, characterised by immunodeficiency and immune dysregulation. Having only been recognised in 2013, evidence on APDS is limited. We carried out four systematic literature reviews (SLRs) to identify and narratively synthesise evidence on the following for APDS: epidemiology (epidemiology SLR), clinical efficacy/safety of treatments (clinical SLR), cost-effectiveness and costs/healthcare (HCRU) associated with (economic SLR) and health-related quality of life (HRQoL) and utility data (HRQoL SLR) from a global perspective.

Methods: The Cochrane Collaboration and the University of York's Centre for Reviews and Dissemination (CRD) guidelines were followed. MEDLINE, Embase, the Cochrane Library, University of York CRD, conference proceedings and other grey literature were searched through to May 2023 for all SLRs, except the epidemiology SLR (searched to Nov 2021); economic databases were also searched for the economic and HRQoL SLRs. Eligible records were: primary epidemiology publications (epidemiology SLR), interventional/observational studies of treatments (clinical SLR), cost/HCRU studies/economic evaluations (economic SLR) and HRQoL/utility studies (HRQoL SLR) in people with APDS. Risk of bias was assessed using the Downs and Black checklist (clinical SLR) and the Drummond checklist (economic SLR).

Results: The numbers of unique relevant studies identified were: 0 (epidemiology SLR), 117 (clinical SLR; 87 reported on <5 patients), 2 (economic SLR) and 1 (HRQoL SLR). The clinical SLR reported symptomatic treatments to be only partially effective at controlling APDS manifestations, with variable tolerability. Outcome reporting was heterogeneous and inconsistent, with small sample sizes and patients receiving multiple treatments, limiting interpretation of results. The economic SLR reported a high direct cost of APDS. Additional HRQoL/utility studies are required to evaluate the clinical and HRQoL burden of APDS and the impact of therapies.

Conclusion: Four methodologically robust SLRs identified limited evidence on epidemiology, clinical outcomes, costs and HRQoL in APDS, reflecting its ultra-rare nature and recent recognition. This suggests a need for more rigorous data evaluating the clinical and economic effectiveness of APDS treatments. Outcome reporting was highly heterogeneous and inconsistent across studies, sample sizes were small and patients often received multiple treatments, limiting interpretation of results.