Immunological Features Of Patients Research Articles

Anti-melanoma differentiation-associated gene-5 antibody-positive dermatomyositis with liver dysfunction: a warning sign of higher death risk.

This study aimed to investigate and analyze the clinical and immunological features of patients with anti-melanoma differentiation-associated gene-5 antibody-positive dermatomyositis (MDA5 + DM) complicated with clinical liver dysfunction. A cohort of 85 patients diagnosed with MDA5 + DM admitted into Peking University People's Hospital from 2006 to 2023 were retrospectively enrolled in this study. Clinical characteristics and survival status were collected and analyzed. Clinical liver dysfunction occurred in 28% (24/85) of MDA5 + DM patients. Patients with clinical liver dysfunction were more likely to have muscle impairment (83.3% vs. 52.5%, P = 0.009) and rapidly progressive ILD (72.7% vs. 47.4%, P = 0.027). Lactate dehydrogenase (LDH) (378.5 (296.0,453.8) U/L vs. 280.0 (218.0,355.0) U/L, P = 0.002) and ferritin (FER) (883.0 (279.8,2100.5) ng/mL vs. 293.5.0 (84.0,862.7) ng/mL, P = 0.040) were significantly elevated and total numbers of lymphocytes (827.2 ± 517.2 /μL vs. 1301.8 ± 720.9 /μL, P = 0.042), and CD4 + T cells (403.8 ± 315.9 /μL vs. 548.6 ± 257.7 /μL, P = 0.045) were significantly decreased in patients with clinical liver function. Muscle weakness (OR 5.184, 95% CI 1.305, 20.595, P = 0.019) was identified as an independent risk factor for clinical liver dysfunction. Clinical liver dysfunction was identified as an independent risk factor for poor prognosis in patients with MDA5 + DM (HR = 4.030, 95% Cl 1.233, 13.176, P = 0.021), with an 18-month survival rate of 69%. Liver dysfunction is one of the extramuscular manifestations in patients with MDA5 + DM and might be associated with a poor prognosis.

#1257 Complement system is overactivated in patients with IgA nephropathy after COVID-19

Abstract Background and Aims Since the coronavirus disease of 2019 (COVID-19) pandemic swept across the world, the flare of immune-mediated disease following SARS-CoV-2 infection has emerged rapidly. IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one of the common glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. Method From December 2022 to April 2023, 33 patients with renal biopsy-proven IgAN (Group CoV) at Beijing Anzhen hospital who had experienced COVID-19 before renal biopsy were enrolled. Meanwhile, 44 patients with IgAN (Group non-CoV) diagnosed from December 2018 to April 2019 (the same period in the previous year, with no COVID-19) were enrolled as control. Plasma FHR-5, MBL, C5a, soluble C5b-9, serum Gd-IgA1 and IgA immune complex were detected by enzyme-linked immunosorbent assay. Glomerular staining for FHR-5, C3c, MAC and Gd-IgA1 were detected by immunofluorescence. SARS-CoV-2 nucleocapsid was detected by immunohistochemistry. Clinicopathological and immunological features between the two groups were analyzed. Results The median time between onset of COVID-19 symptoms and the time of renal biopsy was 12 (6, 18) weeks, ranging from 1 to 26 weeks. SARS-CoV-2 nucleocapsid antigen expression in the renal tubular epithelial cells were observed in 11/33 (33.3%) patients. Compared with Group non-CoV, the level of eGFR was significantly lower in Group CoV[67.30 (52.94, 96.43) ml/min per 1.73 m2 vs. 101.04 (74.35, 120.98) ml/min per 1.73 m2, p = 0.010]. Histologically, compared with Group non-CoV, Group CoV presented with more percentages of segmental glomerulosclerosis/adhesion (p = 0.003) and less percentages of mesangial hypercellularity (p = 0.017). The level of plasma level of C5a [16.45 (10.48, 22.07) ng/ml vs. 3.68 (2.70, 4.47) ng/ml], soluble C5b-9 [614.43 (481.66, 770.02) ng/ml vs. 358.08 (304.83, 471.77) ng/ml], FHR5 [4.01 (3.51, 4.48) ug/ml vs. 2.73 (2.25, 3.21) ug/ml]were all significantly higher in Group CoV compared with Group non-CoV, respectively (p < 0.001). Although the plasma level of MBL showed no difference in Group CoV and Group non-CoV, the proportion of high levels of MBL in Group CoV was higher than in Group non-CoV (p = 0.025). Compared with Group non-CoV, the intensity of glomerular MAC deposition was much stronger in Group CoV. There were no significant differences in serum levels of IgA, Gd-IgA1, IgA immune complex between two Groups. However, a greater intensity of Gd-IgA1 deposition in glomerular mesangial and capillary areas has been exhibited in Group CoV than those in Group non-CoV (p = 0.005). Conclusion For IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, which is the first hit, and increased glomerular deposition of Gd-IgA1 is the second hit. We think that these two hits may lead to renal dysfunction and promote renal progression in IgAN patients. It is crucial to emphasize the necessity for long term follow-up in these patients of IgAN after COVID-19. Additionally, we propose that inhibitors targeting the mediators of complement activation might be a promising therapy for these IgAN patients after SARS-CoV-2 infection.

Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders.

Isolated airway smooth muscle has been extensively investigated since 1840 to understand the pharmacology of airway diseases. There has often been poor predictability from murine experiments to drugs evaluated in patients with asthma or chronic obstructive pulmonary disease (COPD). However, the use of isolated human airways represents a sensible strategy to optimise the development of innovative molecules for the treatment of respiratory diseases. This review aims to provide updated evidence on the current uses of isolated human airways in validated in vitro methods to investigate drugs in development for the treatment of chronic obstructive respiratory disorders. This review also provides historical notes on the pioneering pharmacological research on isolated human airway tissues, the key differences between human and animal airways, as well as the pivotal differences between human medium bronchi and small airways. Experiments carried out with isolated human bronchial tissues in vitro and ex vivo replicate many of the main anatomical, pathophysiological, mechanical and immunological characteristics of patients with asthma or COPD. In vitro models of asthma and COPD using isolated human airways can provide information that is directly translatable into humans with obstructive lung diseases. Regardless of the technique used to investigate drugs for the treatment of chronic obstructive respiratory disorders (i.e., isolated organ bath systems, videomicroscopy and wire myography), the most limiting factors to produce high-quality and repeatable data remain closely tied to the manual skills of the researcher conducting experiments and the availability of suitable tissue.

Molecular and immunological characteristics of patients with CMTM6 low expression colorectal cancer.

CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), a regulator of programmed cell death ligand 1 (PD-L1), has attracted extensive attention due to its role in tumors. However, research on the expression of CMTM6 in colorectal cancer (CRC) and its relationship with PD-L1 expression and immune cell infiltration is limited. We used The Cancer Genome Atlas database to mine and analyze data from patients with CRC using bioinformatics methods. We investigated the expression of CMTM6 in CRC and its relationship with PD-L1 expression and immune cell infiltration. Immunohistochemistry and PCR were performed to detect CMTM6 and PD-L1 expression in CRC tissues. Differential gene expression analysis was performed using the edgeR package in R and immune cell infiltration analysis was performed using the ssGSEA algorithm. Additionally, GO and KEGG enrichment analyses were conducted to identify the biological processes and pathways associated with low CMTM6 expression. Our study found that CMTM6 expression was significantly upregulated in CRC tissues compared to that in adjacent normal tissues. Patients with high CMTM6 expression exhibited significantly increased levels of PD-L1 expression and higher levels of tumor-infiltrating immune cells compared to patients with low CMTM6 expression. GO and KEGG analyses suggested that CMTM6 may be involved in multiple immune regulatory pathways in CRC.

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Background: Sunflower seed is one of the most common edible seeds and its consumption is growing. Case reports of sunflower seed allergy have been described since the 1970s. However, there are few data on the prevalence and clinical manifestations of sunflower seed allergy. Objective: To improve understanding of sunflower seed allergy. Methods: We evaluated the clinical and immunological features of patients with sunflower seed allergy diagnosed in the Allergy Department of a tertiary hospital in Madrid over a 5-years period. Results: Forty-seven patients reported adverse reactions after ingestion of sunflower seed and had specific sensitization to sunflower seed determined by skin prick test (median 8 mm) or specific IgE (median 1.10 kUA/L). Most had an adult-onset reaction to sunflower seed preceded by a history of atopy and other food allergies, predominantly to peach, peanut and nuts. Clinical presentation of sunflower seed allergy ranged from mild to severe, with a high proportion of patients suffering severe reactions, often undertreated. A variability in the severity of symptoms was seen on repeated exposures to sunflower seed on a same patient. Levels of sunflower seed IgE were strongly correlated with levels of IgE to non-specific lipid transfer proteins, while no significant differences were found in the severity of the reactions according to sensitization to those proteins. Conclusion: Our findings reveal a variability of clinical presentations of sunflower seed allergy on repeated exposures and an underuse of epinephrine in anaphylaxis. We highlight the importance of strict avoidance of sunflower seed and accurate prescription and administration of epinephrine in allergic patients.

Clinical and immunological characteristics of patients with moderate COVID-19 with different lung lesion areas

Objective: to study the clinical and immunological parameters of patients with COVID-19 in moderate form with varying degrees of lung tissue damage.Materials and methods: 80 patients hospitalized with a diagnosis of «COVID-19, moderate form; complication: bilateral polysegmental interstitial pneumonia» were examined. The difference in laboratory parameters (general clinical, biochemical and immunological) was evaluated depending on the degree of lung damage (up to 25 and up to 50%). Comparison group: 20 healthy volunteers.Results: the differences between patients with different lung lesion areas consisted in higher levels of prognosis severity markers – CRP, LDH. In the immune status in the CT group 2, there was a decrease in CD3+ lymphocytes and their helper subpopulation, dysimmunoglobulinemia and a higher IL-6 content.Conclusions: CT examination is of great importance for monitoring the progression of the disease. The smaller area of lung lesion reflects a lighter course of the disease, which does not exclude the need for dispensary observation and rehabilitation after discharge.

Combination of NK and Other Immune Markers at Early Phase Stratify the Risk of Sepsis Patients: A Retrospective Study.

Immune dysfunction plays a pivotal role in sepsis pathogenesis. Previous studies have revealed the crucial role of T cells and human leukocyte antigen-DR (HLA-DR) in sepsis. However, the function of natural killer (NK) cells remains unclear. This study aimed to investigate whether NK cells are associated with sepsis prognosis. In addition, we aimed to explore the interrelation and influence between NK and other immunological features in patients with sepsis. This retrospective, observational study included patients with sepsis from two hospitals in mainland China. The clinical characteristics and immune results during the early phase were collected. Patients were classified according to the level of immune cells to analyze the relationship between immunological features and 28-day mortality. A total of 984 patients were included in this study. Non-survivors were older and had lower levels of lymphocytes, monocytes, NK cells, HLA-DR, and T cells. Patients were classified into eight groups according to their levels of NK cells, HLA-DR, and T cells. Only patients with decreased NK and T cell counts showed a significant increase in 28-day mortality. An increase in CD8+ T cells was correlated with the alleviation of 28-day mortality only among patients with high NK cell levels. This study provides novel insights into the association between NK cells and 28-day mortality as well as the interrelation between NK cells and other immune cells in sepsis. The relationship between CD8+ T cells and 28-day mortality in sepsis is dependent on NK cell count.

Identification of immune-related hub genes and construction of an immune-related gene prognostic index for low-grade glioma.

Low-grade glioma (LGG) poses significant management challenges and has a dismal prognosis. While immunotherapy has shown significant promise in cancer treatment, its progress in glioma has confronted with challenges. In our study, we aimed to develop an immune-related gene prognostic index (IRGPI) which could be used to evaluate the response and efficacy of LGG patients with immunotherapy. We included a total of 529 LGG samples from TCGA database and 1152 normal brain tissue samples from the GTEx database. Immune-related differentially expressed genes (DEGs) were screened. Then, we used weighted gene co-expression network analysis (WGCNA) to identify immune-related hub genes in LGG patients and performed Cox regression analysis to construct an IRGPI. The median IRGPI was used as the cut-off value to categorize LGG patients into IRGPI-high and low subgroups, and the molecular and immune mechanism in IRGPI-defined subgroups were analysed. Finally, we explored the relationship between IRGPI-defined subgroups and immunotherapy related indicators in patients after immunotherapy. Three genes (RHOA, NFKBIA and CCL3) were selected to construct the IRGPI. In a survival analysis using TCGA cohort as a training set, patients in the IRGPI-low subgroup had a better OS than those in IRGPI-high subgroup, consistent with the results in CGGA cohort. The comprehensive results showed that IRGPI-low subgroup had a more abundant activated immune cell population and lower TIDE score, higher MSI, higher TMB score, lower T cell dysfunction score, more likely benefit from ICIs therapy. IRGPI is a promising biomarker in the field of LGG ICIs therapy to distinguish the prognosis, the molecular and immunological characteristics of patients.

Clinical and immunological characteristics of patients with combined anti-glomerular basement membrane disease and IgA nephropathy.

The combination of anti-glomerular basement membrane (GBM) disease and immunoglobulin A nephropathy (IgAN) has been well documented in sporadic cases, but lacks overall assessment in large collections. Herein, we investigated the clinical and immunological characteristics and outcome of this entity. Seventy-five consecutive patients with biopsy-proven anti-GBM disease from March 2012 to March 2020 were screened. Among them, patients with concurrent IgAN were identified and enrolled. The control group included biopsied classical anti-GBM patients during the same period, excluding patients with IgAN, other glomerular diseases or tumors, or patients with unavailable blood samples and missing data. Serum IgG and IgA autoantibodies against GBM were detected by enzyme-linked immunosorbent assay, as were circulating IgG subclasses against GBM. Fifteen patients with combined anti-GBM disease and IgAN were identified, accounting for 20% (15/75) of all patients. Among them, nine were male and six were female, with an average (± standard deviation) age of 46.7±17.3 years. Thirty patients with classical anti-GBM disease were enrolled as controls, with 10 males and 20 females at an average age of 45.4±15.3 years. Patients with combined anti-GBM disease and IgAN had restricted kidney involvement without pulmonary hemorrhage. Compared with classical patients, anti-GBM patients with IgAN presented with significantly lower levels of serum creatinine on diagnosis (6.2±2.9 vs 9.5±5.4mg/dL, P=.03) and less occurrence of oliguria/anuria (20%, 3/15 vs 57%, 17/30, P=.02), but more urine protein excretion [2.37 (1.48, 5.63) vs 1.11 (0.63, 3.90) g/24h, P=.01]. They showed better kidney outcome during follow-up (ESKD: 47%, 7/15 vs 80%, 24/30, P=.03). The autoantigen and epitope spectrum were comparable between the two groups, but the prevalence of circulating anti-α3(IV)NC1 IgG1 (67% vs 97%, P=.01) and IgG3 (67% vs 97%, P=.01) were lower in patients with IgAN. Concurrent IgAN was not rare in anti-GBM disease. Patients showed milder kidney lesions and better recovery after immunosuppressive therapies. This might be partly explained by lower prevalence of anti-GBM IgG1 and IgG3 in these patients.

Integrative analyses of bulk microarray data to discover genes, pathways, and immune infiltration characteristics associated with targeting of Ewing sarcoma

PurposeTo explore transcriptome and immunological features of patients with Ewing sarcoma (ES) using all publicly available microarray data.MethodsData of 479 ES tissues were integrated and normalized. Gene expression, immune infiltration, and cancer-specific pathways were analyzed. Genes of interest were knocked down, followed by cell proliferation and colony formation assays.ResultsConsistent with the previous reports of differential expressed genes (DEGs) in ES, our analysis identified CCND1, HMCN1, and NKX2-2 were among the most highly expressed, while TWNC1, MYBPC1, and CKM were among the lowest expressed genes. GO, KEGG, and GSEA enrichment analysis identified that the DEGs related to bone and muscle functioning, those that contributed to crucial cellular, and metabolism pathways such as actin binding, apoptosis, TCA cycle, and cell cycle were also significantly enriched. Immune infiltration analysis discovered that many T cell subsets including CD4T, CD8 T, and Gamma delta T cells were highly infiltrated, while monocytes and B cells were less infiltrated in tumors. A total of 138 genes were both significantly up-regulated in tumors and associated with decreased survival, while 38 significantly down-regulated genes were associated with increased survival, many of which were previously reported as oncogenes and tumor suppressors in ES and other cancers. Silencing of four newly identified top ranked up-regulated genes with decreased survivals in ES inhibited proliferation and colony formation of ES cells.ConclusionThis study may provide a clear representative transcriptome profile of ES, providing diagnostic biomarkers, pathways, and immune infiltrative characteristics targets for ES.

Identification of autoimmune markers in pulmonary tuberculosis.

Pathogenesis of many autoimmune diseases is mainly promoted by poorly regulated and/or wrong targeted immune response to pathogens including M. tuberculosis. Autoimmunity is one of the processes with are characteristics of tuberculosis (Tbc). The aim was to determine the autoimmune clinical and immunological features in patients with pulmonary Tbc. A prospective comparative study was performed in 2017 - 2019 with the inclusion of 46 patients with Tbc. The trigger factors and clinical manifestations, autoantibodies, peripheral blood B cell subsets were stained with fluorochrome-conjugated monoclonal antibodies. 40 healthy volunteers in the control group, were matched for age with no chronic diseases, contacts with TB patients and changes in their laboratory parameters. A statistical analysis was done with GraphPad Prism 6, Statistica 10 (Statsoft) and MedCalc - version 18.2.1 values. There were no significant ASIA triggers in Tbc patients and control group. 21.1% of Tbc patients had a high level of a rheumatoid factor and in 47.4% complement system factor C3 was high; anti-MCV was detected in 60.7% of Tbc patients. Relative and absolute frequencies of "naïve" Bm1 cells and eBm5 were significantly decreased and activated pre-germinal-center Bm2' cells were significantly increased in Tbc patients. The CD24++CD38++ B cells were increased in Tbc vs control group (10.25% vs 5.42%), p < 0.001, and 19 cell/1μL (10; 290 vs 11 cell/1μL (6; 20), p = 0.029, respectively). The frequency of CXCR3+CCR4- Tfh1 cells was significantly lower in Tbc vs control one (26.52% vs. 31.00%, p = 0.004), while CXCR3-CCR4+ Tfh2 cells were increased in Tbc (20.31% vs. controls (16.56%, p = 0.030). The absolute numbers of Tfh1 cells were decreased in the Tbc vs. control (24 cell/1μL vs. 37 cell/1μL p = 0.005). The results of our study showed that the detection of a rheumatoid factor, the components of complement system and anti-MCV in complex with alterations in B cells and follicular Th cell subsets may indicate a presence of autoimmunity in the pathogenesis of tuberculosis, but they are not specific. The indicators of autoimmune-related provide new opportunities in the Tbc treatment.

New aspects of clinical and immunological characteristics in patients with anti-asparaginyl tRNA synthetase (anti-KS) autoantibody.

Anti-asparaginyl tRNA synthetase (anti-KS) antibody is present in patients with interstitial lung disease (ILD) accompanied by polymyositis/dermatomyositis. We examined clinical/immunological features of these patients. Polymyositis/dermatomyositis or ILD patients were screened for autoantibodies, and clinical/immunological data were collected retrospectively. ILD was diagnosed by computed tomography, and clinical/immunological features of anti-KS-positive patients were compared with those of anti-Jo-1-positive patients. Sixteen anti-KS-positive patients [female = 11; male = 5; average age 63.6 years (range, 40-81) years] were diagnosed: seven had ILD, four had clinically amyopathic DM (CADM) and ILD, three had Sjögren's syndrome (SS) and ILD one each had rheumatoid arthritis and ILD, or CADM/SS overlap and ILD. All patients had ILD with chronic onset and clinical course; 11/16 (69%) had nonspecific interstitial pneumonia, and five (31%) had usual interstitial pneumonia pattern. Regarding skin manifestations, 4 (27%) had typical DM rash and 11 (69%) had mechanic's hands. All anti-KS-positive patients had no clinical muscle weakness or serum creatine kinase elevation; 8/16 patients (50%) had sicca symptoms at a significantly high frequency compared with anti-Jo-1-positive patients (50% vs 11%, P = 0.01). Anti-KS-positive patients might form a distinguishable subset closely associated with sicca symptoms, CADM and chronic-type ILD with a relatively favourable prognosis.

X-linked agammaglobulinemia: 35 years of experience in a tertiary pediatric hospital in Latin America

Background: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by arrested B cell development, leading to reduced numbers of B lymphocytes and serum immunoglobulin (Ig) levels, due to mutations in the BTK gene located on the X chromosome (Xq21.3- Xq22). The aim of this study was to describe the clinical and immunologic characteristics of patients with a diagnosis of XLA, seen in a tertiary pediatric hospital in Mexico in the department of immunodeficiency in the last 35 years.Methods: A cross-sectional, retrospective and observational study of patients diagnosed with XLA with follow-up in a reference hospital in Mexico City, in a period of January-1987 to July-2022 was performed, data related to their disease status were taken and statistical analysis were analyzed using SPSS.V.16.0.Results: Information was collected from 44 patients with the diagnosis of XLA. The age of onset was 24 months. The age at diagnosis was 60 months. A delay in diagnosis of 37 months was identified, 54 % of patients required I.V. antibiotics before diagnosis, and 45% had a family member with immunodeficiency. The mean Ig levels were IgG: 359 mg/dl, IgA: 24 mg/dl, and IgM: 25 mg/dl. The 77% had a history of bacterial infections before diagnosis, and 6% had allergic symptoms. The main infection was pneumonia in 75%, acute otitis media in 50%, sinusitis in 59%, meningitis in 13%, cutaneous abscesses in 15%, 36% percent developed complications such as bronchiectasis, and 31% sepsis. Once the diagnosis was established, all patients received Immunoglobulin replacement therapy (IRT). 47% of patients were administered antibiotic prophylaxis.Conclusions: The diagnosis of XLA should be suspected in a patient with recurrent clinical manifestations of encapsulated bacterial infections. The diagnosis is confirmed with serum immunoglobulin levels, two standard deviations below for age, when the flow cytometry is available it can help with the diagnosis. The first contact physician can make the diagnosis.

Primary Gougerot-Sjogren Syndrome at the Moulay Ismail Military Hospital in Meknes: Epidemiological, Clinical and Immunological Aspects

Introduction: Gougerot Sjögren's syndrome (GSS) is a connective tissue disease characterized by lymphocytic infiltration of the exocrine glands, and systemic manifestations of an immuno-inflammatory nature. This infiltration is predominant in the salivary and lacrimal glands, responsible for dry mouth and eyes. Clinically, the dry syndrome characteristic of SS may be mild or even absent, and extra glandular systemic manifestations may be the main circumstance in which this connective tissue is discovered. The diagnosis is based on a bundle of arguments, clinical, histological and immunological. SS is characterized by the fairly frequent presence of autoantibodies whose diagnostic value is indisputable, and some of which testify to the activity of the disease. In addition, these autoantibodies may have a correlation with certain organ damage as well as certain progressive forms. The objective of this work is to determine, through a retrospective and comparative study, the epidemiological, clinical and immunological characteristics of patients with primary Gougerot Sjögren's syndrome (SGSp) followed in the internal medicine department of the Military Hospital. Moulay Ismail from Meknes (HMIM), Morocco. Patients and Methods: We report a retrospective study of patients with primary Gougerot-Sjörgen syndrome followed in the internal medicine department of the Moulay Ismail military hospital (Meknes), over a period of 08 years (January 2010 - December 2018). All patients meeting AECG diagnostic criteria were included. Results: 13 cases of S.G.Sp are collected. There was a clear predominance of the female sex, with 12 women (92.3%) and 01 man (7.69%), sex ratio (F/M=12/1). The average age at diagnosis was 48 years with extremes ranging from 20 to 60 years? The clinical picture was dominated by dry syndrome in 100% of cases associated with inflammatory polyarthralgia found in 76.9% of cases. The immunological profile was variable with positive ANA in 61.5% of cases, .......

Diagnostic accuracy of the European League against rheumatism/American College of Rheumatology-2019 versus the Systemic Lupus International Collaborating Clinics-2012 versus the ACR-1997 classification criteria in adult systemic lupus erythematosus: A systematic review and meta-analysis.

AimTo evaluate the diagnostic performance of the American College of Rheumatology (ACR)-1997, the Systemic Lupus International Collaborating Clinics (SLICC)-2012, and the European League against Rheumatism (EULAR)/ACR-2019 classification criteria in adult patients with systemic lupus erythematosus (SLE).MethodsPubMed, Embase, Web of Science and Cochrane Library databases were searched for literature comparing the three classification criteria of ACR-1997, SLICC-2012 and EULAR/ACR-2019, which took clinical diagnosis as reference. Meta-analysis was used to evaluate and compare the sensitivity, specificity and diagnostic odds ratio of ACR-1997, SLICC-2012 and EULAR/ACR-2019. To assess the early diagnosis capability of the classification criteria, subgroups of patients with disease duration < 3 years and < 1 year were selected for comparison of sensitivity and specificity based on the inclusion of the original study. The sensitivity and specificity of each item in three sets of classification criteria were evaluated. In addition, the clinical and immunological characteristics of patients who did not meet the three classification criteria were compared.ResultsNine original studies were included in the analysis, including 6404 SLE patients and 3996 controls. Results showed that the diagnostic odds ratios (95% confidence interval) of the SLICC-2012 [136.35 (114.94, 161.75)] and EULAR/ACR-2019 [187.47 (158.00, 222.42)] were higher than those of the ACR-1997 [67.53 (58.75, 77.63)]. Compared with ACR-1997[(0.86 (0.82, 0.89)], SLICC-2012[(0.96 (0.93, 0.97)] and EULAR/ACR-2019[(0.95 (0.92, 0.97)] had higher sensitivity. The specificity of the three classification criteria was similar: ACR-1997, SLICC-2012, and EULAR/ACR-2019 were 0.93 (0.89, 0.95), 0.86 (0.79, 0.91), and 0.91 (0.85, 0.95), respectively. The sensitivity of SLICC-2012 and EULAR/ACR-2019 were higher than that of ACR-1997 in early-course subgroups. Patients who did not meet ACR-1997 had more hypocomplementemia, patients who did not meet SLICC-2012 had more cutaneous lupus and photosensitivity, and patients who did not meet EULAR/ACR-2019 had more cutaneous lupus and leucopenia.ConclusionsSLICC-2012 and EULAR/ACR-2019 have better diagnostic ability than the ACR-1997, and the sensitivity of the former two criteria is also higher than that of the latter; Moreover, the SLICC-2012 and EULAR/ACR-2019 for patients in the early stages of disease performed equally excellent.

Immunological Characteristics of Patients Receiving Ultra-Short Treatment for Chronic Hepatitis C.

Reducing the treatment duration for chronic hepatitis C could be an important tool in the effort to reach the elimination goals set by the World Health Organization. The current challenge is to predict the target group who will achieve sustained virological response at week 12 (SVR12) with shorter treatment duration. The aim of this exploratory study was to characterize immune subsets with focus on inhibitory receptors in patients who experienced SVR12 or virological relapse following four weeks treatment with glecaprevir/pibrentasvir with or without ribavirin. A total of 32 patients were included in this study of whom 21 achieved SVR12 and 11 had virological relapse. All available samples at baseline (n = 31) and end of treatment (EOT) (n = 30) were processed for flow cytometric analysis in order to measure the expression of PD-1, 2B4, BY55, CTLA-4, TIM-3 and LAG-3 on 12 distinct T cell subsets. At baseline, patients with SVR12 (n=21) had numerically lower frequencies of inhibitory receptors for 83% (60/72) of the investigated T-cell subtypes. The most significant difference observed between the two groups was a lower frequency of stem cell-like memory T-cells CD4+PD1+ in the SVR group (p = 0.007). Furthermore, we observed a significant positive correlation between baseline viral load and the expression of PD-1 on the total CD8+ T-cells and effector memory T-cells CD4+ and CD8+ for patients with virological relapse. This study suggests a measurable immunologic phenotype at baseline of patients achieving SVR12 after short treatment compared to patients with virological relapse.

Comparison of Clinical Manifestations, Immunological Analyses Between LRBA and CVID Patients: A Longitudinal Study

Background: Common variable immunodeficiency (CVID), is generally recognized as the most frequent type of Symptomatic primary immunodeficiencies (PID). Mutations in lipopolysaccharideresponsive beige-like anchor protein (LRBA) gene, are the most common genetic alterations amongst CVID patients. To date, there are no published studies to compare clinical and immunologic features of LRBA-deficient patients with those who do not harbor any known genetic mutations. Therefore, this study aims to compare the clinical manifestations and laboratory findings of Iranian patients with LRBA-deficiency and CVID with no known genetic alterations. Methods: We performed a longitudinal study on patients who had been diagnosed with CVID. Demographic and clinical features were obtained via the databank of the Iranian Registry of Primary Immunodeficiencies, and the direct interviews with patients. To assess the presence of LRBA or other genetic mutations, whole-exome sequencing (WES) was used. Immunologic characteristics of patients were evaluated using flow cytometry, nephelometry, and conventional blood counts. The current study is conducted at Tehran’s Children Medical Center and is approved by the ethics committee of Tehran University of Medical Sciences. Results: Between March 2013 and October 2019, we enrolled 30 patients with LRBA-deficiency and 13 patients with CVID, who had no identified genetic mutations. Regarding clinical features, there were no significant differences for the prevalence of infections at different sites (lung, sinuses, and middle ear) among the two groups (all P-values &gt; 0.05). However, the incidences of autoimmune disorders and enteropathy were significantly higher among LRBA-deficient cases (P &lt; 0.001). In serum levels of immunoglobulins, there were significant differences for IgG and IgM between the two groups (P-values of 0.014 and 0.004, respectively); however, this was not seen for IgA and IgE levels. Likewise, we did not see any significant differences for the cluster of differentiation (CD) markers between the two groups (all P-values &gt; 0.05). Conclusion: Compared to the CVID patients with no identified genetic mutations, LRBA-deficient patients have a significantly greater chance of parental consanguinity and developing autoimmune disorders and enteropathy, and have significantly higher values of serum IgG and IgM. The rate of infectious complications and other basic laboratory features, do not show significant differences between the two groups.

Analyses of the clinical and immunological characteristics of patients with lupus erythematosus.

Background:Lupus erythematosus (LE) is a broad-spectrum, heterogeneous disease. At one end of the spectrum is the cutaneous LE (CLE) without systemic involvement, and at the other end is the systemic LE (SLE) with multisystem involvement. Analyses of clinical and immunological indicators and pathological examinations are helpful for early diagnosis, differential diagnosis, and prognosis of LE.Aim and Objectives:We described the clinical and laboratory characteristics of patients with LE and assessed the diagnostic value of immunohistochemical detection of C3d, C4d, IgG, IgG4, and CD123 in skin lesions of LE.Materials and Methods:Clinical and laboratory data of 62 patients with LE were collected. The expression levels of C3d, C4d, IgG, IgG4, and CD123 in skin lesions of LE were detected by immunohistochemistry (IHC).Results:Clinical manifestations such as hematological involvement, C3, C4, ESR, hematuresis, proteinuria, anti-Sm, anti-ribosomal P-protein, anti-U1-RNP, anti-histone, and anti-nucleosome antibodies are helpful for classificatory diagnosis of LE. The positive rate of C3d and/or C4d along the basement membrane zone in LE skin lesions by IHC was 74.6%, which was higher than that by direct immunofluorescence (47.5%) (P = 0.002). The expression of CD123 protein and the number of CD123+ plasmacytoid dendritic cells (PDCs) in skin lesions of patients with LE were higher than those of dermatomyositis (DM), while the distributed form of CD123 + PDCs in the dermis was different between LE and DM.Conclusions:The diagnosis of CLE and SLE requires a combination of clinical manifestations, laboratory indicators, and pathological examination. Immunohistochemical detection of C3d, C4d, and CD123 in skin lesions is important for the classificatory diagnosis of LE.

Low IgG trough and lymphocyte subset counts are associated with hospitalization for COVID-19 in patients with primary antibody deficiency

Low IgG trough and lymphocyte subset counts are associated with hospitalization for COVID-19 in patients with primary antibody deficiency

Problems of creating predictive models of the COVID19 coronavirus pandemic

Relevance. The article is devoted to creating prognostic models based on epidemiological and immunological data. Objective: to study the comparative dynamic epidemiological and immunological characteristics of patients with COVID-19. Materials and methods. Methodological approaches to the use of system analysis of epidemiological and immunological characteristics of patients with COVID-19 using multivariate analysis are described. The used technologies of computer-aided analysis systems, algorithms for recognizing, measuring and identifying the condition of patients, and methods of statistical data processing made it possible to create a universal information predictive model for calculating the dynamics of infectious diseases prone to generalization (pandemics), as well as to understand in which groups these new infectious diseases are most dangerous. Results and discussion. Using the methods of system analysis, the epidemiological and immunological aspects of predictive models of the coronavirus pandemic were evaluated using the most objective international data, which increased the information content of the analysis. Conclusions . Creating predictive epidemiological and immunological models of the pandemic is an urgent and promising task to combat the medical and social consequences of the spread of coronavirus infection in Russia.