Age-and Sex-matched Healthy Controls Research Articles

Evaluation of Urinary Free Light Chains as a Marker of Severity of HIV Disease and Its Correlation with CD4 Count: A Pilot Study.

Human immunodeficiency virus (HIV) infection weakens immunity. Monitoring the immune status of the patient has become an important aspect of evaluating the progression of the disease and informing follow-up after treatment. Estimation of CD4 counts is quite costly and requires expertise in flow cytometry. In certain pathologies, free light chains (FLCs) are secreted in serum and urine and the magnitude can be used to monitor the severity, progression, and therapeutic monitoring of the disease. Urine as a specimen proves cost-effective and presents reduced risks during sample collection. The stability of light chains in urine at room temperature over extended periods simplifies the management of sample transportation as well. Hence, a pilot cross-sectional study was planned to evaluate the levels of urinary immunoglobulins in patients with HIV. The study was conducted at PGIMER, Dr. Ram Manohar Lohia Hospital (presently ABVIMS), New Delhi. Sixty-nine consecutive ART-naive HIV patients aged between 18 and 40 years and 69 age- and sex-matched healthy controls were included in the study. Urinary FLC kappa (κ) and lambda (λ) were measured using an immunoglobulin ELISA kit. Baseline urinary κ light chain levels were significantly higher in cases when compared with controls (p < .001) and were found to be increased with increasing WHO immunological classes (p < .001) and inversely related to CD4 cell count. However, no significant difference in mean urinary λ immunoglobulin light chain between cases and controls was found and no correlation with CD4 cell count or with stages of WHO immunological classification of HIV disease was observed. It is suggested that urinary free κ chain measurements combined with serum light chain measurements may be a useful marker in the follow-up and monitoring of response to therapies in patients with HIV where testing by flow cytometry is not available.

Aberrant baseline cytokine profile in patients with newly diagnosed acquired aplastic anaemia correlates with disease severity and the treatment response

BackgroundImmune dysregulation is crucial in the pathogenesis of acquired aplastic anaemia (aAA). There is paucity of data regarding correlation of baseline cytokine profile with treatment response in aAA. ObjectivePresent prospective case-control study aimed to correlate the baseline cytokines in patients with aAA with the treatment response. MethodsFifty-one patients with newly-diagnosed aAA > 13 years of either sex were enrolled over 1.5 years. Twenty age-and sex-matched healthy controls (HC) were also included. The cytokine profile (IL-2, 4, 6, 8, 10, 17, IFN-γ and TNF-α) in the peripheral blood plasma of aAA patients was performed at the baseline using cytometric bead analysis. The cytokine levels were compared with HC and correlated with response to immunosuppressive therapy (IST) at 3-months. ResultsThe median age of cases was 29 years (range,13–74). The cases had higher mean levels of IL2 (p = 0.326), IL4 (p = 0.038), IL6 (p = 0.000), IL10 (p = 0.002), TNF-α (p = 0.302), IFN-γ (p = 0.569) and IL-17 (p = 0.284) than the HC. The baseline levels of all the cytokines were higher (statistically non-significant) among responders (n = 13) than the non-responders (n = 14) to IST. ConclusionsBaseline cytokine profile in patients with aAA might predict response to the IST. Larger studies are needed to validate our results.

Evaluating high-resolution computed tomography derived 3-D joint space metrics of the metacarpophalangeal joints between rheumatoid arthritis and age- and sex-matched control participants.

Rheumatoid arthritis (RA) is commonly characterized by joint space narrowing. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides unparalleled in vivo visualization and quantification of joint space in extremity joints commonly affected by RA, such as the 2nd and 3rd metacarpophalangeal joints. However, age, sex, and obesity can also influence joint space narrowing. Thus, this study aimed to determine whether HR-pQCT joint space metrics could distinguish between RA patients and controls, and determine the effects of age, sex and body mass index (BMI) on these joint space metrics. HR-pQCT joint space metrics (volume, width, standard deviation of width, maximum/minimum width, and asymmetry) were acquired from RA patients and age-and sex-matched healthy control participants 2nd and 3rd MCP joints. Joint health and functionality were assessed with ultrasound (i.e., effusion and inflammation), hand function tests, and questionnaires. HR-pQCT-derived 3D joint space metrics were not significantly different between RA and control groups (p > 0.05), despite significant differences in inflammation and joint function (p < 0.05). Joint space volume, mean joint space width (JSW), maximum JSW, minimum JSW were larger in males than females (p < 0.05), while maximum JSW decreased with age. No significant association between joint space metrics and BMI were found. HR-pQCT did not detect group level differences between RA and age-and sex-matched controls. Further research is necessary to determine whether this is due to a true lack of group level differences due to well-controlled RA, or the inability of HR-pQCT to detect a difference.

Evaluation of semicircular canal and otolith graviceptive pathway function in patients diagnosed with motion sickness disorder based on the diagnostic criteria of the Bárány society

Objective: To investigate the altered function of the semicircular canal and otolith graviceptive pathway in patients diagnosed with motion sickness disorder (MSD) based on the diagnostic criteria of the Bárány society, and explore its relevance to the pathogenesis of MSD. Methods: This is a case-control study. Twenty patients with MSD and age-and sex-matched healthy controls without a history of MSD from the Department of Neurology of Aerospace Center Hospital between March and August 2022 were recruited. All subjects completed the motion sickness susceptibility questionnaire-short version (MSSQ-short) and the motion sickness assessment questionnaire (MSAQ). Canal function was evaluated using caloric stimulation test and video head impulse test (vHIT), and subjective visual vertical/horizontal (SVV/SVH) and vestibular evoked myogenic potential (VEMP) were employed to assess otolith graviceptive function. Differences in vestibular function and correlations between the two groups were analyzed. Results: Each group consisted of 20 cases (9 males and 11 females). The mean age of the MSD and control groups was (26.9±3.9) years and (27.0±3.4) years, respectively. The scores of MSSQ-short [27.0 (22.5, 38.8) vs 1.2 (0, 3.2), P<0.001] and MSAQ [70.1 (54.5, 78.1) vs 11.8 (11.1, 13.9), P<0.001] were significantly higher in the MSD group compared with those of the control group. Evaluation of canal function revealed a significantly higher incidence of caloric stimulation intolerance in MSD patients (60.0%, 12/20) compared with that of the control group (20.0%, 4/20) (P=0.010). Evaluation of otolith graviceptive pathway indicated no significant difference in SVV, SVH and cervical VEMP (cVEMP) abnormality rates between the two groups (all P>0.05). The ocular VEMP (oVEMP) abnormality rate was significantly higher in the MSD group (55.0%, 11/20) than that of the control group (10.0%, 2/20) (P=0.002), with a delayed P1-wave latency compared with the control group [(18.4±1.2) ms vs (17.6±0.8) ms, P=0.018]. Further correlation analysis revealed that P1-wave latency in oVEMP was positively correlated with MSSQ-short (r=0.486, P=0.002) and MSAQ (r=0.391, P=0.015) scores, and duration of caloric intolerance symptoms (r=0.377, P=0.004). Conclusion: The presence of hypersensitivity to caloric stimulation and delayed latency of otolith function in patients with MSD suggests a "separation" between semicircular canal and otolithic function, which may be related to sensory conflict.

CD32 (FcγRIIB) expression is low on CD21low B cells from systemic sclerosis patients with digital ulcers, interstitial lung disease, and anti-topoisomerase I autoantibodies

CD21low B cells have recently been found increased in SSc-associated digital ulcers (DUs) or interstitial lung disease (ILD). To further characterize CD21low B cells which encompass autoreactive cells, we analyzed their expression of the inhibitory CD32 receptor in SSc. Peripheral blood mononuclear cells from 27 patients with SSc and 15 age-and sex-matched healthy controls (HCs) were analyzed with multicolor flow cytometry. CD21low B cells were significantly increased in patients with DUs (51.3%) compared to HCs (28.1%) and in patients with ILD (53.1%) compared to HCs. CD21lowCD32low B cells were significantly increased in patients with DUs (23.8%) compared to HCs (4.4%), in patients with ILD (28.4%) compared to HCs, and in anti-topoisomerase I (+) patients (21.5%) compared to HCs and to anti-topoisomerase I (−) patients (2.4%). Autoreactive B cells recognizing Topoisomerase I were predominantly within CD32low cell fraction. Our study further supports the autoreactive status of CD21lowCD32low B cells in SSc patients.

Assessment of PD-1 and PD-L1 tissue expression levels in lichen planus patients: a case–control study

Programmed cell death protein-1 (PD-1) is an immune checkpoint protein, PD-1 interaction with PD ligand-1 (PD-L1) is essential for maintaining immunological tolerance. The study aimed to study and compare the levels of PD-1 and PD-L1 in lesional and nonlesional skin of lichen planus (LP) patients and compare these levels to normal healthy controls to assess their role in the pathogenesis of LP. This case–control study involved 30 patients with LP and 30 healthy age-and sex-matched controls. After clinical assessment of the severity by LP severity index score (LPSI), skin biopsies were taken from lesional and nonlesional skin of LP patients and from normal skin in healthy controls for assessment of the tissue levels of PD-1 and PD-L1 by ELISA. The tissue levels of both PD-1 and PD-L1 were significantly higher in healthy controls than in both lesional and nonlesional skin of LP patients (P < 0.001). Also, significantly higher PD-l and PD-L1 levels in nonlesional skin than in lesional skin of LP patients were reported (P < 0.001). No significant correlations were found between lesional and nonlesional PD-1, PD-L1 levels, or LPSI score. Based on the fact that PD-1/PD-L1 interaction is important to maintain tolerance and protection against autoimmune diseases, in addition to our study results that revealed lower levels of PD-1/PD-L1 in LP skin than in healthy skin, we can conclude that PD-1/PDL-1 may be incriminated in the pathogenesis of LP. ClinicalTrials.govID: NCT04892381.

Serum Neopterin, Biopterin, Tryptophan, and Kynurenine Levels in Patients with Fabry Disease

Fabry disease is characterized by the accumulation of globotriaosylceramide. Substrate accumulation in lysosomes is thought to trigger an inflammatory response and is responsible for progressive organ damage through the induction of autoimmunity. The levels of pteridine and kynurenine pathway metabolites increase when immune activation is observed and are employed to monitor several diseases and determine prognosis. To elucidate the effects of immune activation on the pathophysiology of Fabry disease and to investigate the potential utility of pteridine and kynurenine metabolites. A prospective case-control study. In this study, 33 patients with Fabry disease and 33 age-and sex-matched healthy controls were included. Blood pteridine and kynurenine metabolites were studied in both groups. Organ involvement in Fabry disease and its correlation with the pteridine and kynurenine pathways were also investigated. The patients’ neopterin and biopterin levels and the tryptophan/kynurenine ratio were statistically higher than those of the healthy control group (p < 0.05). A statistically significant association was found between neopterin levels and hypertrophic cardiomyopathy, cardiac arrhythmias, and GFR values (p = 0.044, p = 0.021, and p = 0.030, respectively), tryptophan and corneal verticillate, hearing loss and tinnitus (p = 0.010, p = 0.009 and p = 0.046, respectively), and kynurenine levels and valvular heart disease (p = 0.020). From the onset of the disease, patients with Fabry disease exhibited elevated levels of inflammation and immune activation. Furthermore, inflammation and immune activation markers can be used as early disease biomarkers.

Abstract TP84: Characteristics of Cerebellar Cognitive Affective Syndrome in Patients With Acute Cerebellar Stroke and Its Impact on Outcome

Background: Recently, cerebellar cognitive affective syndrome-scale (CCAS-S) was developed to assess CCAS in which cognitive impairment is caused by cerebellar lesions. However, very few studies have been conducted regarding CCAS in patients with stroke, and its impact on outcomes is unclear. This study aimed to evaluate CCAS in patients with acute cerebellar stroke and examine its association with outcome. Methods: Patients who experienced acute cerebellar stroke for the first time and were admitted to Steel Memorial Yawata Hospital, Japan within seven days of stroke onset between April 2021 and April 2023 were included in this observational study. CCAS-S, Mini-Mental State Examination (MMSE), and Scale for Assessment and Rating of Ataxia (SARA) scores were measured one week after stroke onset, and Functional Independence measure (FIM)/ Barthel Index (BI) at discharge, physical function, activities of daily living, length of hospital stay, and outcome (discharge destination) were evaluated. The Mann-Whitney U test was used to compare CCAS-S scores and other variables between patients with acute cerebellar stroke and healthy controls. Additionally, we compared these variables between patients discharged home and those discharged to a rehabilitation hospital. A significance level of less than 5%. Results: Thirteen consecutive patients with acute cerebellar stroke (9 women) and age-and sex-matched healthy controls (7 women) were included. The MMSE score was within the normal range in all patients; however, patients with stroke had a lower total CCAS-S score (median 72, interquartile range [IQR] 66-80) and a higher number of failed tests (median 4, IQR 3-5) than healthy controls. Significant deficits were observed in semantic fluency (p=0.008), category switching (p=0001), and similarity (p=009). Possible, probable, and definite CCAS were diagnosed in 2, 1, and 10 patients, respectively. Patients discharged home showed better SARA and FIM/BI scores but similar CCAS-S scores compared to those discharged to rehabilitation hospitals. Conclusion: CCAS along with impaired executive and language functions is frequently observed in patients with acute cerebellar stroke; however, impaired motor function, and not CCAS, influenced the outcome.

Assessing brain microstructural changes in chronic kidney disease: a diffusion imaging study using multiple models.

To explore the effectiveness of diffusion quantitative parameters derived from advanced diffusion models in detecting brain microstructural changes in patients with chronic kidney disease (CKD). The study comprised 44 CKD patients (eGFR<59 mL/min/1.73 m2) and 35 age-and sex-matched healthy controls. All patients underwent diffusion spectrum imaging (DSI) and conventional magnetic resonance imaging. Reconstructed to obtain diffusion MRI models, including diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) and Mean Apparent Propagator (MAP)-MRI, were processed to obtain multi-parameter maps. The Tract-Based Spatial Statistics (TBSS) analysis was utilized for detecting microstructural differences and Pearson correlation analysis assessed the relationship between renal metabolism markers and diffusion parameters in the brain regions of CKD patients. Receiver operating characteristic (ROC) curve analysis assessed the diagnostic performance of diffusion models, with AUC comparisons made using DeLong's method. Significant differences were noted in DTI, NODDI, and MAP-MRI parameters between CKD patients and controls (p < 0.05). DTI indicated a decrease in Fractional Anisotropy(FA) and an increase in Mean and Radial Diffusivity (MD and RD) in CKD patients. NODDI indicated decreased Intracellular and increased Extracellular Volume Fractions (ICVF and ECVF). MAP-MRI identified extensive microstructural changes, with elevated Mean Squared Displacement (MSD) and Q-space Inverse Variance (QIV) values, and reduced Non-Gaussianity (NG), Axial Non-Gaussianity (NGAx), Radial Non-Gaussianity (NGRad), Return-to-Origin Probability (RTOP), Return-to-Axis Probability (RTAP), and Return-to-Plane Probability (RTPP). There was a moderate correlation between serum uric acid (SUA) and diffusion parameters in six brain regions (p < 0.05). ROC analysis showed the AUC values of DTI_FA ranged from 0.70 to 0.793. MAP_NGAx in the Retrolenticular part of the internal capsule R reported a high AUC value of 0.843 (p < 0.05), which was not significantly different from other diffusion parameters (p > 0.05). The advanced diffusion models (DTI, NODDI, and MAP-MRI) are promising for detecting brain microstructural changes in CKD patients, offering significant insights into CKD-affected brain areas.

Altered gut microbiota and metabolites in untreated myasthenia gravis patients.

The homeostasis of the immune system is influenced by the gut microbiota. Previous studies have reported dysbiosis in the gut microbiota of myasthenia gravis (MG) patients. To investigate potential alterations in gut microbiota and metabolites in newly diagnosed and untreated MG patients, we conducted a case-control study. Fecal samples were collected from 11 newly diagnosed and untreated MG patients as well as 11 age-and sex-matched healthy controls. These samples underwent analysis for gut microbiota using 16S ribosomal RNA (rRNA) gene sequencing, while fecal metabolome was analyzed using liquid chromatography-electrospray tandem mass spectrometry system (LC-ESI-MS/MS). The microbial community richness (observed species) and diversity (Shannon and Simpson indices) were significantly lower in the MG group compared to the control group. Microbiota composition analysis revealed significant differences between the MG and control groups at phylum, family, and genus levels. Linear discriminant analysis effect size (LEfSe) analysis showed a substantial decrease in abundance of the genus Faecalibacterium within the MG group. Fecal metabolome analysis identified three up-regulated metabolites involved in amino acid metabolism (taurine, creatinine, L-carnitine), one up-regulated metabolite involved in lipid metabolism (oleic acid), with correlation analysis indicating a positive association between Faecalibacterium abundance and creatinine levels. Our findings suggest that dysbiosis already exists in newly diagnosed and untreated MG patients, implying that dysbiosis within the gut microbiota may be an initiating factor contributing to MG pathogenesis. Furthermore, F. prausnitzii may hold promise as a probiotic for treating MG.

Differences In Cardiopulmonary Exercise Testing Responses Between Patients With Sarcoidosis And Age-and Sex-matched Healthy Controls

Differences In Cardiopulmonary Exercise Testing Responses Between Patients With Sarcoidosis And Age-and Sex-matched Healthy Controls

Validity and reliability of the Sinhalese version of the perceived stress scale questionnaire among Sri Lankans.

Despite the availability of validated psychometrics tools to assess depression, there has not been any validated and reliable tool established to test perceived stress among Sri Lankans. The objective of this study is to test the validity and reliability of the Sinhalese Version of the Sheldon Cohen Perceived Stress Scale. Standard and systematic procedures were adopted to translate the original English version of the Perceived Stress Scale-10 questionnaire into Sinhalese. Consecutive sampling was employed to recruit the Type 2 Diabetes mellitus (T2DM) sample (n = 321), and a convenient sampling was used to recruit the Age and Sex matched Healthy Controls (ASMHC) (n = 101) and the Healthy Community Controls (HCC) groups (n = 75). Cronbach alpha was used to assess internal consistency and reliability was determined using test-retest method utilizing Spearman's correlation coefficient. Sensitivity was evaluated by comparing the mean scores of the Sinhalese Perceived Stress Scale (S-PSS-10) and Sinhalese Patient Health Questionnaire (S-PHQ-9) scores. Post-hoc comparisons were done using Bonferroni's method. Mean scores were compared between the T2DM, ASMHC, and HCC groups using the independent t-test. Explanatory Factor Analysis (EFA) was conducted using the principal component and Varimax rotation while the Confirmatory Factor Analysis (CFA) was performed to assess the goodness-of-fit of the factor structure extracted from the EFA. Concurrent validity was assessed using the Pearson correlation between the S-PSS-10 and Patient Health Questionnaire measured by S-PHQ-9 (p < 0.05). Cronbach alpha values of the three groups T2DM, ASMHC and HCC were 0.85, 0.81, and 0.79, respectively. Results of the ANOVA test suggested that there was a significant difference in the mean scores between groups (p < 0.00). EFA analysis revealed the existence of two factors with eigenvalues greater than 1.0. The factor loadings for the items ranged from 0.71-0.83. The CFA analysis demonstrated a good model fit for the two-factor model S-PSS-10. The S-PSS-10 significantly correlated with S-PHQ-9, indicating an acceptable concurrent validity. Findings revealed that the S-PSS-10 questionnaire can be used to screen perceived stress among the majority of the Sri Lankan Sinhalese-speaking population specially with chronic illnesses. Further studies with higher sample sizes across different populations would enhance the validity and reliability of S-PSS-10.

FGR methylation in blood as a potential marker for the pre-clinical detection of early lung cancer: A case-control study.

e20500 Background: Lung cancer (LC) is the leading cause of cancer-related death. Although low-dose computed tomography (LDCT) is a routine clinical test for early detection of LC, it can introduce excessive false positives. DNA specific methylation identification in peripheral blood can be used for noninvasive diagnosis and monitoring. Therefore, We applied a candidate approach and assess the association between blood-based FGR methylation and the risk of lung cancer in a case–control cohort. Methods: A total of 426 patients with LC and 428 age-and sex-matched healthy controls were recruited from two hospitals to collect peripheral blood and clinical information. The methylation levels of four CPG sites in FGR gene were determined by quantitative mass spectrometry. Linear regression models were used to estimate the association between DNA methylation site levels and lung cancer. And stratified analysis of age and sex. Results: It was found that the hypermethylation of FGR_CPG1 and FGR_CPG2 was associated with early LC (OR = 1.60 (95%CI: 1.35, 1.89, p = 5.35E-08) and 1.08 (95%CI: 1.01, 1.16, p = 3.58E-02), respectively). These associations persist in patients with very early LC (stage I). Stratified analysis showed that the association between hypermethylation of FGR_CPG2 and LC was only found in men and subjects younger than 55 years of age. Conclusions: This work reveals a novel association between aberrant FGR gene methylation in blood and early LC. These results suggest that FGR gene methylation may be used to predict early lung cancer and provide guidance for the prevention and control of lung cancer.

White matter microstructural abnormalities in individuals with attenuated positive symptom syndromes

White matter (WM) microstructural alterations have been extensively studied in patients with psychosis, but research on the microstructure of WM in individuals with attenuated positive symptom syndrome (APSS) is currently limited. To improve the understanding of the neuropathology in APSS, this study investigated the WM of individuals with APSS using diffusion tensor and T1-weighted imaging. Automated fiber quantification was used to calculate the diffusion index values along the trajectories of 20 major fiber tracts in 42 individuals with APSS and 51 age-and sex-matched healthy control (HC) individuals. The diffusion index values in each of fiber tracts were compared node-by-node between the 2 groups. Compared with the HC group, the APSS group showed differences in the diffusion index values in partial segments of the callosum forceps minor, left and right cingulum cingulate, inferior fronto-occipital fasciculus, right corticospinal tract, left superior longitudinal fasciculus, and arcuate fasciculus. Notably, in the APSS group positive associations were found between the axial diffusivity values of the partial nodes of the left and right cingulum cingulate and the current Global Assessment of Functioning scores, as well as between the axial diffusivity values of the partial nodes of the right corticospinal tract and negative symptoms scores and reasoning and problem-solving scores. These findings suggest that individuals with APSS exhibit reduced WM integrity or possible impaired myelin in certain segments of WM tracts involved in the frontal- and limbic-cortical connections. Additionally, abnormal WM tracts appear to be associated with impaired general function and neurocognitive function. This study provides important new insights into the neurobiology of APSS and highlights potential targets for future intervention and treatment.

Is there any correlation between alpha-synuclein levels in tears and retinal layer thickness in Parkinson's disease?

To determine the total alpha-synuclein (αSyn) reflex tears and its association with retinal layers thickness in Parkinson's disease (PD). Fifty-two eyes of 26 PD subjects and 52 eyes of age-and sex-matched healthy controls were included. Total αSyn in reflex tears was quantified using a human total αSyn enzyme-linked immunosorbent assay (ELISA) kit. The retinal thickness was evaluated with spectral-domain optical coherence tomography. The Movement Disorder Society-Unified Parkinsońs Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS), and Montreal Cognitive Assessment (MoCA) were used to assess motor, non-motor, and cognition. In PD, total αSyn levels were increased compared to control subjects [1.76pg/mL (IQR 1.74-1.80) vs 1.73pg/mL (IQR 1.70-1.77), p < 0.004]. The nerve fiber layer, ganglion cell layer, internal plexiform layer, inner nuclear layer, and outer nuclear layer were thinner in PD in comparison with controls (p < 0.05). The outer plexiform layer and retinal pigment epithelium were thicker in PD (p < 0.05). The total αSyn levels positively correlated with the central volume of the inner nuclear layer (r = 0.357, p = 0.009). Total αSyn reflex tear levels were increased in subjects with PD compared to controls. PD patients showed significant thinning of the inner retinal layers and thickening of outer retinal layers in comparison with controls. Total αSyn levels positively correlate with the central volume of the inner nuclear layer in PD. The combination of these biomarkers might have a possible role as a diagnostic tool in PD subjects.

Role of HLA-DPrs3077 and HLA-DQrs3920 Polymorphisms as Risk Factors for Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is a chronic disease caused by the destruction of insulin-producing pancreatic β-cells. During disease progression, inflammatory insulitis increases the presentation of islet antigens on human leukocyte antigen (HLA) molecules to T lymphocytes. This complex system plays a pivotal role in cellular immunity. Thus, genetic variability in HLA can affect the susceptibility to and clinical outcomes of DM. This case-control study aimed to assess the role of HLA-DP-rs3077 (A/G) and HLA-DQrs3920 (A/G) polymorphism in T1DM. This study enrolled 400 individuals: 200 patients with T1DM and 200 ageand sex-matched healthy controls. Hemoglobin A1C and random, fasting, and postprandial blood sugar levels were determined for all subjects. Genotypic and allelic distributions of HLA-DPrs3077 (A/G) and HLA-DQrs3920 (A/G) SNPs were determined using real-time polymerase chain reaction (PCR). Frequency of the HLA-DPrs3077A allele was high among the diabetic group (91.3%); however, the difference was non-significant [OR (95% C.I) = 1.422(0.89-2.252), P=0.098]. The frequency of the HLA-DQrs3920 GG genotype was higher in control than the diabetic group (52.5% vs.12%), whereas that of the AA genotype was higher in the person with diabetes than in the control group (34% vs.4%). Individuals carrying the HLA-DQrs3920A allele were 4.5 times more likely to have T1DM than those carrying the G allele [OR (95% C.I) = 4.510 (3.338- 6.094), P<0.001*]. The presence of HLA-DPrs3077A and HLA-DQ rs3920A in the same person increases T1DM risk by 3.6 times that of G allele [OR (95%C.I) = 3.608(2.173-5.991), P<0.001*]. HLA-DPrs3077 and HLA-DQrs3920 SNPs have a role in T1DM as the coexistence of HLA-DPrs3077A and HLA-DQrs3920A alleles increases the risk.

Single-Cell RNA and TCR Sequencing Reveals Novel Immune Cell Networks in Poorly Controlled Epilepsy (S35.001)

<h3>Objective:</h3> To perform a deep dissection of the role and regulation of innate and adaptive immunity in poorly controlled (PC) and well controlled (WC) focal epilepsy. <h3>Background:</h3> The role of the immune system in the pathophysiology of epilepsy has been underappreciated. There is mounting evidence that surgical epilepsy samples contain infiltrating immune cells. However, their phenotype and the mechanism of their recruitment are not well understood. <h3>Design/Methods:</h3> Individuals with focal epilepsy were prospectively recruited from Brigham and Women’s Hospital outpatient epilepsy clinics. Epilepsy subjects were divided into a WC or PC group based on whether they had seizures within the 6 months prior to study enrollment. Age-and sex-matched healthy controls were also included. Using peripheral blood mononuclear cells (PBMCs), we performed a detailed analysis of ~84,000 PBMCs using single-cell RNA and T-cell receptor sequencing (scRNA/TCR-seq). <h3>Results:</h3> A total of 107 subjects were recruited including 87 epilepsy subjects and 20 healthy controls. 49.5% of epilepsy subjects had a seizure within 6 months of recruitment, and 52% had an MRI abnormality. scRNA/TCR-seq data highlighted differences in the composition of adaptive and innate immune cells in well-controlled and poorly-controlled subjects. In particular, memory CD4+ and CD8+ T-cells as well as NK T-cells that express cytotoxic cytokines such as granzyme and perforin, constitute a higher proportion of T-cells in PC epilepsy subjects, whereas CD14+ and CD16+ monocytes, and B memory cells show depletion. Moreover, ligand/receptor network analyses using the CellChat computational tool identified several statistically significant intercellular interactions such as the Selectin cell adhesion pathway that is involved in the recruitment of leukocytes to the site of injury in the brain. <h3>Conclusions:</h3> We identified disrupted adaptive and innate immune homeostasis in poorly controlled focal epilepsy. Network analyses revealed ligand/receptor pairs with well-known roles in lymphocyte trafficking that may be targeted for immunomodulatory interventions to treat epilepsy. <b>Disclosure:</b> Dr. Sarkis has nothing to disclose. Ms. Amer has nothing to disclose. Mr. Mares has nothing to disclose. Mr. Hobson has nothing to disclose. The institution of Vilas Menon has received research support from Chan Zuckerberg Initiative. The institution of Vilas Menon has received research support from National Institute of Aging. Vilas Menon has received personal compensation in the range of $0-$499 for serving as a Grant Reviewer with National Institutes of Health. Dr. Pennell has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for American Epilepsy Society. The institution of Dr. Pennell has received research support from NIH. The institution of an immediate family member of Dr. Pennell has received research support from Department of Defense. The institution of an immediate family member of Dr. Pennell has received research support from Environmental Protection Agency. The institution of an immediate family member of Dr. Pennell has received research support from NIH. The institution of an immediate family member of Dr. Pennell has received research support from Advanced Energy Consortium. Dr. Pennell has received publishing royalties from a publication relating to health care. Dr. Elyaman has nothing to disclose.

Correlation between gene polymorphisms of killer cell immunoglobulin-like receptors and their ligands and Graves' disease

Objective: To explore the relationship between gene polymorphism of killer cell immunoglobulin-like receptor (KIR) and its ligand-specific human leukocyte antigen C (HLA-C) and Graves' disease (GD). Methods: Case-control study. A total of 118 unrelated GD patients (GD group) admitted to Shandong Provincial Hospital from January 2011 to December 2017 and 108 age-and sex-matched healthy controls (healthy control group) were included. The KIR genotype and its ligand HLA-C allele were detected by polymerase chain reaction sequence-specific primers (PCR-SSP). The distribution of KIR/HLA-C gene combination in GD patients and control population was analyzed to explore its association with the occurrence of GD. Results: In GD group, there were 29 males and 89 females, aged (38±14) years. In the healthy control group, there were 28 males and 80 females, aged (37±13) years. Compared with the healthy control group, the occurrence frequency of HLA-Cw01 was higher in GD group[36.4%(43/118) vs 18.5%(20/108), P=0.003], and the occurrence frequency of HLA-Cw03 and HLA-Cw06 was lower in GD group[11.9%(14/118) vs 39.8%(43/108), P<0.001; 9.3%(11/118) vs 18.5%(20/108), P=0.045]. The frequency of KIR2DL1/HLA-C2 gene combination in GD group was lower than that in control group [17.8%(21/118) vs 34.3%(37/108), P=0.005]. Logistic regression analysis showed that KIR2DL1/HLA-C2 gene combination was a protective factor for GD occurrence (OR=0.308, 95%CI: 0.126-0.752, P=0.010). Conclusions: The polymorphism of KIR/HLA-C gene is related to GD. The low expression of KIR2DL1/HLA-C2 in GD patients may be a protective factor for GD.

The Peripheral Immune Traits Changed in Patients with Multiple System Atrophy

A growing body of evidence suggests immune involvement in the pathology of multiple system atrophy (MSA). Research on detailed peripheral immune indices, however, is relatively sparse, and is one of the intriguing aspects of MSA yet to be elucidated. A total of 26 MSA patients and 56 age-and sex-matched healthy controls (HC) were enrolled in the current case-control study to delineate the peripheral immune traits of MSA patients. The ratio of CD4+/CD8+ T cells, natural killer cells, CD28 expression on both CD4+ T cells and CD8+ T cells increased in MSA patients compared to HC, but CD8+ T cells and active marker (HLA-DR) expression on total T cells decreased (p < 0.05). This study sheds light on the dysregulation of cellular immunity in MSA, pointing to future mechanistic research.

Metabolic pathway analysis of hyperuricaemia patients with hyperlipidaemia based on high-throughput mass spectrometry: a case‒control study

BackgroundBoth hyperuricaemia and hyperlipidaemia are common metabolic diseases that are closely related to each other, and both are independent risk factors for the development of a variety of diseases. HUA combined with hyperlipidaemia increases the risk of nonalcoholic fatty liver disease and coronary heart disease. This study aimed to investigate the relationship between HUA and hyperlipidaemia and study the metabolic pathway changes in patients with HUA associated with hyperlipidaemia using metabolomics.MethodsThis was a case‒control study. The prevalence of hyperlipidaemia in HUA patients in the physical examination population of Tianjin Union Medical Centre in 2018 was investigated. Metabolomics analysis was performed on 308 HUA patients and 100 normal controls using Orbitrap mass spectrometry. A further metabolomics study of 30 asymptomatic HUA patients, 30 HUA patients with hyperlipidaemia, and 30 age-and sex-matched healthy controls was conducted. Differential metabolites were obtained from the three groups by orthogonal partial least-squares discrimination analysis, and relevant metabolic pathways changes were analysed using MetaboAnalyst 5.0 software.ResultsThe prevalence of hyperlipidaemia in HUA patients was 69.3%. Metabolomic analysis found that compared with the control group, 33 differential metabolites, including arachidonic acid, alanine, aspartate, phenylalanine and tyrosine, were identified in asymptomatic HUA patients. Pathway analysis showed that these changes were mainly related to 3 metabolic pathways, including the alanine, aspartate and glutamate metabolism pathway. Thirty-eight differential metabolites, including linoleic acid, serine, glutamate, and tyrosine, were identified in HUA patients with hyperlipidaemia. Pathway analysis showed that they were mainly related to 7 metabolic pathways, including the linoleic acid metabolism pathway, phenylalanine, tyrosine and tryptophan biosynthesis pathway, and glycine, serine and threonine metabolism pathway.ConclusionsCompared to the general population, the HUA population had a higher incidence of hyperlipidaemia. HUA can cause hyperlipidaemia. by affecting the metabolic pathways of linoleic acid metabolism and alanine, aspartate and glutamate metabolism. Fatty liver is closely associated with changes in the biosynthesis pathway of pahenylalanine, tyrosine, and tryptophan in HUA patients with hyperlipidaemia. Changes in the glycine, serine and threonine metabolism pathway in HUA patients with hyperlipidaemia may lead to chronic kidney disease.