Predictive utility of ANCA positivity and antigen specificity in the assessment of kidney disease in paediatric-onset small vessel vasculitis.

OBJECTIVES: The objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive utility in paediatric-onset small vessel vasculitis. METHODS: Children and adolescents with small vessel vasculitis (n=406) stratified according to the absence (n=41) or presence of ANCA for myeloperoxidase (MPO) (n=129) and proteinase-3 (PR3) (n=236) were compared for overall and kidney-specific disease activity at diagnosis and outcomes between 1 and 2 years using retrospective clinical data from the ARChiVe/Paediatric Vasculitis Initiative registry to fit generalised linear models. RESULTS: Overall disease activity at diagnosis was higher in PR3-ANCA and MPO-ANCA-seropositive individuals compared with ANCA-negative vasculitis. By 1 year, there were no significant differences, based on ANCA positivity or specificity, in the likelihood of achieving inactive disease (~68%), experiencing improvement (≥87%) or acquiring damage (~58%). Similarly, and in contrast to adult-onset ANCA-associated vasculitis, there were no significant differences in the likelihood of having a relapse (~11%) between 1 and 2 years after diagnosis. Relative to PR3-ANCA, MPO-ANCA seropositivity was associated with a higher likelihood of kidney involvement (OR 2.4, 95% CI 1.3 to 4.7, p=0.008) and severe kidney dysfunction (Kidney Disease Improving Global Outcomes (KDIGO) stages 4-5; OR 6.04, 95% CI 2.77 to 13.57, p<0.001) at onset. Nonetheless, MPO-ANCA seropositive individuals were more likely to demonstrate improvement in kidney function (improved KDIGO category) within 1 year of diagnosis than PR3-ANCA seropositive individuals with similarly severe kidney disease at onset (p<0.001). CONCLUSIONS: The results of this study suggest important paediatric-specific differences in the predictive value of ANCA compared with adult patients that should be considered when making treatment decisions in this population.

CD28null T cells in aging and diseases: From biology to assessment and intervention.

CD28null T cells, an atypical subset characterized by the loss of CD28 costimulatory molecule expression, exhibit functional variants and progressively expand with age. Moreover, T cells with these phenotypes are found in both typical and atypical humoral immune responses. Consequently, they accumulate during infectious diseases, autoimmune disorders, cardiovascular conditions, and neurodegenerative ailments. To provide an in-depth review of the current knowledge regarding CD28null T cells, we specifically focus on their phenotypic and functional characteristics as well as their physiological roles in aging and diseases. While uncertainties regarding the clinical utility remains, we will review the following two crucial research perspectives to explore clinical translational applications of the research on this specific T cell subset: 1) addressing the potential utility of CD28null T cells as immunological markers for prognosis and adverse outcomes in both aging and disease, and 2) speculating on the potential of targeting CD28null T cells as an interventional strategy for preventing or delaying immune aging processes and disease progression.

Coexistence of Hashimoto's Thyroiditis in Differentiated Thyroid Cancer: Post-Operative Monitoring of Anti-Thyroglobulin Antibodies and Assessment of Treatment Response.

INTRODUCTION: Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto's thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. METHODS: This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. RESULTS: Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. CONCLUSIONS: While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship.

Assessment of serum granulysin and cathepsin-L levels in vitiligo patients

SUMMARY OBJECTIVE: Cellular and humoral immunity plays a role in the pathogenesis of vitiligo. T lymphocytes and natural killer cells involved in cellular immunity carry out their cytotoxic activities through perforin/granzyme-dependent granule exocytosis, in which granulysin and cathepsin-L are also involved. The aim of this study was to investigate the possible role of serum granulysin and cathepsin-L in the etiopathogenesis of vitiligo and their association with disease activity and severity. METHODS: This randomized, prospective case-control study was conducted with 46 vitiligo patients admitted to the hospital for vitiligo between January and November 2021 and 46 healthy volunteers of similar age and gender. Serum levels of granulysin and cathepsin-L were measured by the enzyme-linked immunosorbent assay method. RESULTS: The mean serum levels of granulysin and cathepsin-L were statistically significantly higher in vitiligo patients compared with the control group (p=0.048 and p=0.024, respectively). There was no statistically significant correlation between serum granulysin and serum cathepsin-L levels and disease severity in the patient group (r=0.30, p=0.062 and r=0.268, p=0.071, respectively). Disease activity also showed no significant association with serum granulysin and cathepsin-L levels (p=0.986 and p=0.962, respectively). CONCLUSION: Although granulysin and cathepsin-L are molecules involved in the pathogenesis of vitiligo, the use of these molecules may not be helpful in assessing disease activity and severity. It may be helpful to conduct comprehensive and prospective studies to find new molecules to fill the gap in this area.

CXADR polymorphism rs6517774 modifies islet autoimmunity characteristics and exhibits sex disparity.

Enteroviral infections have been linked to the development of islet autoimmunity (IA) and type 1 diabetes (T1D), and the coxsackie and adenovirus receptor (CXADR) is one of the ligands used by adenoviruses and enteroviruses for cell internalization. Two CXADR single nucleotide polymorphisms (SNPs), rs6517774 and rs2824404, were previously associated with an increased susceptibility to IA in the international TEDDY study (The Environmental Determinants of Diabetes in the Young). This study aimed to replicate the results by genotyping 2886 children enrolled in the Finnish Diabetes Prediction and Prevention study (DIPP). In our preliminary analysis of the SNPs' allelic distributions, we could not find any association with IA susceptibility. However, a stratified analysis revealed a sex disparity, since the allelic distribution of rs6517774 was different when comparing autoantibody positive females with males; a difference not seen in healthy subjects. By using HLA risk groups and sex as covariates, a Cox regression survival analysis found that the rs6517774 (A/G) SNP was associated with a lower age at seroconversion in females (Female*rs6517774-AA; HR = 1.53, p = 0.002), while introducing a protective effect in males. Accordingly, we propose that rs6517774 alters IA characteristics by modifying the age at seroconversion in a sex-dependent manner. In light of this observation, rs6517774 now joins a limited set on SNPs found to introduce sex-dependent risk effects on the age at IA initiation.

Assessment of autoantibodies in paediatric population with primary immunodeficiencies: a pilot study.

BACKGROUND: The correlation between primary immunodeficiencies (PIDs) and autoimmunity shows ethnic and geographical diversity. The aim of our study was to accumulate more data in paediatric PID population. METHODS: 58 children aged 1-17 and with PID (study group) and 14 age-matched immunocompetent individuals (control group) were included in the study. Serum levels of 17 different specific IgG antibodies against autoantigens were measured by means of a quantitative enzyme immunoassay. Immunoglobulin levels were analysed in relation to a detailed medical examination. RESULTS: Autoantibodies against one or more antigens were detected in the sera of 24.14% (n = 14) subjects in the study group. The most frequent were anti-thyroid peroxidase (anti-TPO) antibodies (n = 8; 13.8%). Anti-TPO antibody levels were elevated more often in PID patients with a positive family history of autoimmune diseases (p = 0.04). The screening for anti-deamidated gliadin peptide (DGP) and anti-tissue transglutaminase (tTG) antibodies in our series allowed identifying two previously undiagnosed cases of coeliac disease in PID patients. There was no statistically significant difference between the study and the control group in terms of the autoantibodies prevalence. CONCLUSIONS: This study provides data on the prevalence of autoantibodies in paediatric population diagnosed with PID. Selected autoantibodies (i.e. anti-tTG, anti-DGP) might be useful for the screening of PID to avoid the delay of diagnosis of an autoimmune disease.

Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance.

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune diseases of the thyroid gland, causing hyperthyroidism and hypothyroidism, respectively. Despite their opposing clinical manifestation, they have several enigmatic links. Here, we propose that GD and HT have the same fundamental origin: both diseases are the cost of a beneficial physiological process called autoimmune surveillance of hypersecreting mutants. Autoreactive T cells selectively eliminate mutant cells that hypersecrete the hormones and threaten to become toxic nodules. These T cells can trigger a humoral response in susceptible individuals, leading to the production of antibodies against thyroid antigens. This shared origin can explain similarities in incidence and risk factors between HT and GD, despite their opposite clinical phenotypes.

Brief report: Assessment of mucosal barrier integrity using serological biomarkers in preclinical stages of rheumatoid arthritis.

Background: The pathogenesis of rheumatoid arthritis (RA) is believed to initiate at mucosal sites. The so-called 'mucosal origin hypothesis of RA' postulates an increased intestinal permeability before disease onset. Several biomarkers, including lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP), have been proposed to reflect gut mucosa permeability and integrity, while serum calprotectin is a new inflammation marker proposed in RA. Methods: We analyzed serum samples of individuals genetically at increased risk of RA in a nested-case-control study. Participants from a longitudinal cohort of first-degree relatives of RA patients (SCREEN-RA cohort) were divided into three pre-clinical stages of RA, based on the presence of risk factors for subsequent RA onset: 1) low-risk healthy asymptomatic controls; 2) intermediate-risk individuals without symptoms, but with RA-associated auto-immunity; 3) high-risk individuals with clinically suspect arthralgias. Five patients with newly diagnosed RA were also sampled. Serum LBP, I-FABP and calprotectin were measured using commercially available ELISA kits. Results: We included 180 individuals genetically at increased risk for RA: 84 asymptomatic controls, 53 individuals with RA-associated autoimmunity and 38 high risk individuals. Serum LBP, I-FAPB or calprotectin concentrations did not differ between individuals in different pre-clinical stages of RA. Conclusion: Based on the serum biomarkers LBP, I-FABP and calprotectin, we could not detect any evidence for intestinal injury in pre-clinical stages of RA.

Ultrasound assessment of degenerative muscle sarcopenia: the University of Barcelona ultrasound scoring system for sarcopenia.

AIM: This study aimed to (1) determine the intraobserver and interobserver reliability of ultrasonographic measurement of muscle thickness (MT) and cross-sectional area (CSA) of the rectus femoris and biceps brachii, correlating these values with manual measurements on dissected cadavers and (2) develop the first semiquantitative musculoskeletal ultrasound (MSUS) scoring system of muscle morphology in sarcopenia and assess its intraobserver and interobserver reliability. In addition, the MSUS morphology score was compared with the corresponding histological images to verify concurrent validity. METHODS: Ten cryopreserved limbs of 10 cadavers aged 68-91 years were evaluated. The MSUS scoring system was based on the severity of muscle degeneration on a 3-point qualitative scale: grade 1 (normal), grade 2 (moderate changes) and grade 3 (severe changes). Reliability was assessed with intraclass correlation coefficient (ICC) for the MT and CSA and with Cohen's kappa coefficients (κ) for the MSUS scoring system. Concurrent validity was analysed with ICC. RESULTS: The results showed excellent intraobserver and interobserver reliability for both the MSUS evaluation of MT and CSA (ICC ≥0.93). The MSUS scoring system showed excellent intraobserver reliability (κ=1.0) and very good interobserver reliability (κ=0.85). There was also a high intra- and inter-observer reliability for the histological scorings (ĸ ≥0.85 and mean ĸ=0.70, respectively), as well as high reliability between the histology and MSUS scoring systems (ICC=0.92). All results were statistically significant (p≤0.001). CONCLUSION: MSUS measures of MT and CSA and the novel MSUS scoring system for degenerative muscle changes in sarcopenia was found to be reliable and strongly associated with histological findings.

Autoimmune and immunoserological markers of COVID-19 pneumonia: Can they help in the assessment of disease severity.

Background: Immune dysregulation and associated inefficient anti-viral immunity during Coronavirus Disease 2019 (COVID-19) can cause tissue and organ damage which shares many similarities with pathogenetic processes in systemic autoimmune diseases. In this study, we investigate wide range autoimmune and immunoserological markers in hospitalized patients with COVID-19. Methods: Study included 51 patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 infection and hospitalized due to COVID-19 pneumonia. Wide spectrum autoantibodies associated with different autoimmune inflammatory rheumatic diseases were analyzed and correlated with clinical and laboratory features and pneumonia severity. Results: Antinuclear antibodies (ANA) positivity was found in 19.6%, anti-cardiolipin IgG antibodies (aCL IgG) in 15.7%, and anti-cardiolipin IgM antibodies (aCL IgM) in 7.8% of patients. Positive atypical x anti-neutrophil cytoplasmic antibodies (xANCA) were detected in 10.0% (all negative for Proteinase 3 and Myeloperoxidase) and rheumatoid factor was found in 8.2% of patients. None of tested autoantibodies were associated with disease or pneumonia severity, except for aCL IgG being significantly associated with higher pneumonia severity index (p = 0.036). Patients with reduced total serum IgG were more likely to require non-invasive mechanical ventilation (NIMV) (p < 0.0001). Serum concentrations of IgG (p = 0.003) and IgA (p = 0.032) were significantly lower in this group of patients. Higher total serum IgA (p = 0.009) was associated with mortality, with no difference in serum IgG (p = 0.115) or IgM (p = 0.175). Lethal outcome was associated with lower complement C4 (p = 0.013), while there was no difference in complement C3 concentration (p = 0.135). Conclusion: Increased autoimmune responses are present in moderate and severe COVID-19. Severe pneumonia is associated with the presence of aCL IgG, suggesting their role in disease pathogenesis. Evaluation of serum immunoglobulins and complement concentration could help assess the risk of non-invasive mechanical ventilation NIMV and poor outcome.

[Association of antithyroid peroxidase antibodies with cardiac function in euthyroid women with type 1 diabetes mellitus - assessment with two-dimensional speckle­tracking echocardiography].

INTRODUCTION: The presence of diabetes is associated with loss of cardioprotection in premenopausal women; however, the mechanisms involved remain unknown. Autoimmune factors are suspected to play a role in cardiovascular complications, especially in type 1 diabetes (T1DM). The aim of this pilot study was to explore whether antithyroid peroxidase antibody (aTPO) as a marker of increased immune activity is related to cardiac dysfunction in young, asymptomatic women with T1DM. MATERIAL AND METHODS: Eighty-eight euthyroid women (59 with T1DM and 29 healthy controls) underwent physical examination, laboratory tests, thyroid ultrasound, and two-dimensional speckle-tracking echocardiography. According to the antiperoxidase antibodies (aTPO) titre, the T1DM women were divided into an aTPO positive (T1DM aTPO+) (n = 34) and an aTPO negative (T1DM aTPO-) (n = 25) group. The relationship between thyroid autoimmunity parameters and echocardiographic parameters was evaluated. RESULTS: Global longitudinal strain (GLS) was slightly reduced in the T1DM aTPO+ group compared to T1DM aTPO- and significantly compared to controls (p = 0.051 and p = 0.015, respectively). Although, the lower values of longitudinal strain of left ventricular were found in the majority of segments in the T1DM aTPO+ group in comparison to T1DM aTPO- and controls, significant differences were only found in the two-chamber view (specifically in the anterior segments) between the T1DM aTPO+ and T1DM aTPO- groups (p = 0.030) and in the four-chamber view (specifically in the anterolateral segments) between the T1DM aTPO+ group and controls (p = 0.021). Echocardiographic parameters of diastolic and systolic function of both ventricles were significantly correlated with parameters of thyroid autoimmunity. A logistic regression analysis showed that Hashimoto's thyroiditis (HT) duration [odds ratio (OR): 0.997, 95% confidence interval (CI): 0.995-0.999, p = 0.008), the dose of levothyroxine (OR: 0.814, 95% CI: 0.689-0.960, p = 0.013), and reduced echogenicity on thyroid ultrasound (OR: 0.309, 95% CI: 0.120-0.793, p = 0.013) had a significant influence on reduced GLS. CONCLUSIONS: Our results suggest that coexistence of aTPO with T1DM was associated with poorer myocardial function, particularly in the anterior and anterolateral segments, which may be related to an autoimmune factor. The impaired function of these segments is probably the first sign of myocardial systolic dysfunction in women with T1DM, which needs to be confirmed in further studies.

Influence of Socio-Demographic Factors in Patients With Cutaneous Lupus Erythematosus.

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune skin disease with potential for systemic involvement, disfigurement, and significant disease burden. The relationships of demographics and socioeconomic status with patients with CLE are emerging topics with important clinical implications. The primary objective of our study is to perform a literature review of studies that have investigated demographic and socioeconomic factors amongst patients with CLE and determine whether these factors influence diagnosis frequency, disease severity and outcomes or health related quality of life. We searched multiple databases to identify literature addressing CLE and concepts such as race, ethnicity, gender, income, education level and geographic location. Information regarding primary research objective was extracted from all full text articles, and a summary of findings was prepared. We found that race and ethnicity can influence CLE diagnosis frequency and disease outcomes. Chronic cutaneous lupus (CCLE) occurs more frequently in Black patients, often with higher overall disease damage. Differences between genders exist in CLE in terms of health-related quality of life, as female gender was a risk factor for worse quality of life in several studies. Lower income, low educational attainment, and lack of health insurance all contribute to poorer overall outcomes in CLE patients. This review will help inform physicians about populations at risk for potentially worse outcomes to guide treatment decisions for patients with CLE and provide important information to design interventions that address modifiable social determinants of health in this population.

Expanded assessment of xenobiotic associations with antinuclear antibodies in the United States, 1988-2012.

BACKGROUND: The prevalence of autoimmunity in the U.S. has increased recently for undetermined reasons. Little is known about associations between autoimmunity and environmental causes. OBJECTIVES: In a large representative sample of the U.S. population, we expanded our prior exploratory study of how exposures to selected xenobiotics and dioxin-like (DL) mixtures relate to antinuclear antibodies (ANA), the most common biomarker of autoimmunity. METHODS: We analyzed cross-sectional data on 12,058 participants aged ≥ 12 years from three time periods of the National Health and Nutrition Examination Survey between 1988 and 2012, of whom 14% were ANA-positive. We used lognormal regression models and censored-data methods to estimate ANA associations with xenobiotic concentrations overall and in sex, age, and race/ethnicity subgroups. Our analyses adjusted for potential confounders and appropriately handled concentrations below detection limits. RESULTS: Observed ANA associations were positive for most DL compounds and nonDL polychlorinated biphenyls (PCBs), negative for most phthalates, and mixed for other xenobiotic classes. After correcting for multiple comparisons, some associations remained statistically significant. In subgroup analyses, the most significant finding was a positive ANA association with N-acetyl-S-(2-hydroxy-3-butenyl)-L-cysteine (MHB2) in males, followed by positive associations with 2,2',3,5'-tetrachlorobiphenyl (PCB 44), 2,2',4,5'-tetrachlorobiphenyl (PCB 49), and 2,2',3,4',5',6-hexachlorobiphenyl (PCB 149) in 12-19 year-olds, and with 3,4,4',5-tetrachlorobiphenyl (PCB 81), 2,2',3,3',4,4',5,5',6-nonachlorobiphenyl (PCB 206), and N-acetyl-S-(phenyl)-L-cysteine (PMA) in Mexican Americans. Negative associations were found with mono-benzyl phthalate (MBzP) in 20-49 year-olds and mono-n-butyl phthalate (MnBP) in 12-19 year-olds. In overall analyses, combining stratum-specific results across race/ethnicity strata revealed a positive ANA association with PCB 81 and a negative ANA association with N-acetyl-S-(2-hydroxyethyl)-L-cysteine (HEMA). DISCUSSION: This study identified potential associations between ANA and various xenobiotics. Further investigation to confirm these observations and elucidate effects of certain xenobiotics on immune regulation could have important mechanistic, preventive, and treatment implications for a variety of immune-mediated disorders.

Assessment of ADAM17 and ADAM10 proteins with CXCL10 and thyroid autoimmunity in vitiligo pathogenesis.

Introduction: Vitiligo is an acquired chronic pigmentation disorder. The etiopathogenesis is still not fully understood. Aim: To research the correlation of ADAM proteins, shown to be associated with autoimmune diseases like rheumatoid arthritis and lupus erythematosus, with vitiligo also considered to be an autoimmune disease. Material and methods: The study included a patient group of 45 patients with the diagnosis of vitiligo and a control group of 45 healthy adults. The ADAM10 and ADAM17 protein serum levels and CXCL10 and thyroid autoantibody anti-TG and anti-TPO levels along with FT3, FT4, and TSH hormone levels were determined with the ELISA method. Statistical analysis of results was made with the SPSS 22.0 program. Results: In vitiligo patients, the ADAM10 levels (2.34 ±0.80 pg/ml) were statistically significantly low compared to the control group (10.29 ±1.71 pg/ml) (p < 0.05), while the ADAM17 levels (128.51 ±14.37 pg/ml) were statistically significantly high compared to the control group (16.30 ±6.31 pg/ml) (p < 0.05). Additionally, the CXCL10 levels were observed to be statistically significantly higher in the patient group (275.11 ±62.36) than in the control group (107.08 ±33.12). Thyroid autoimmunity test results (anti-TG, anti-TPO, and TSH) were shown to be different to a statistically significant degree in the patient group compared to the control group (p < 0.001, p < 0.000, p = 0.003, respectively). Statistical analyses used the Kolmogorov-Smirnov, Mann-Whitney U test, and the independent T-test. Conclusions: We obtained data that are important in terms of understanding the pathogenesis. ADAM10 and ADAM17 proteins may be new targets for future therapeutic approaches.

Clinical measurement of lupus nephritis activity is inferior to biomarker-based activity assessment using the renal activity index for lupus nephritis in childhood-onset systemic lupus erythematosus.

OBJECTIVES: The renal activity index for lupus (RAIL) measures lupus nephritis (LN) activity considering urine levels of 6 biomarkers (neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, kidney injury molecule-1, adiponectin, haemopexin, ceruloplasmin). We aimed to compare the accuracy of the RAIL and the renal domain-score of the SLE disease activity index (rSLEDAI) in detecting LN activity. METHODS: Random urine samples of patients with childhood-onset SLE with and without LN were assayed and scores of the RAIL, and RAIL standardised for urine creatinine (RAIL-Cr) were calculated. Clinical LN activity was measured by the rSLEDAI, and histological activity of LN was categorised as inactive/low-moderate/high for National Institute of Health-activity index scores of <2/2-10/>10, respectively. RESULTS: 115 patients were included in the analysis (47 patients without and 68 with LN). RAIL, RAIL-Cr and rSLEDAI scores at the time (±3 months) of kidney biopsy were available for 32 patients. Median rSLEDAI, RAIL and RAIL-Cr values were 4, -0.04, 0.02 for inactive LN, 12, 0.7 and 0.9 for low-moderate LN activity and 12, 2 and 1.8 for high LN activity, respectively. The area under the receiver operating characteristic curve (AUC) to capture high LN activity was the lowest for the rSLEDAI (AUC=0.62), followed by the RAIL-Cr (AUC=0.73) and RAIL (AUC=0.79). Notably, when testing urine samples collected during routine clinic visits remote (>3 months) from a kidney biopsy, 50% patients with rSLEDAI scores of 0 had RAIL scores reflecting low-moderate LN activity. CONCLUSION: Monitoring of renal inflammation in children and adolescents with SLE can be improved by the measurement of urine biomarkers. The RAIL may constitute important auxiliary tool for the surveillance of LN in a clinical setting and assist with the decision to obtain a kidney biopsy.

SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies.

OBJECTIVE: To evaluate sialic acid binding Ig-like lectin 1 (SIGLEC1) expression on monocytes by flow cytometry as a type I interferon biomarker in idiopathic inflammatory myopathies (IIM). METHODS: We performed a retrospective analysis of adult and paediatric patients with the diagnosis of IIM. SIGLEC1 expression was assessed by flow cytometry and was compared with Physician Global Assessment or Childhood Myositis Assessment Scale disease activity scores. Mann Whitney U test and receiver operating characteristic curves were used for cross-sectional data analysis (n=96), two-level mixed-effects linear regression model for longitudinal analyses (n=26, 110 visits). Response to treatment was analysed in 14 patients within 12 months, using Wilcoxon test. SIGLEC1 was compared with interferon-stimulated gene 15/MxA status by immunohistochemical staining of muscle biopsies (n=17). RESULTS: 96 patients with adult (a) and juvenile (j) dermatomyositis (DM, n=38), antisynthetase syndrome (AS, n=19), immune-mediated necrotising myopathy (IMNM, n=8), inclusion body myositis (IBM, n=9) and overlap myositis (n=22) were included. SIGLEC1 distinguished significantly between active and inactive disease with an area under the curve of 0.92 (95% CI 0.83 to 1) in DM and correlated with disease activity longitudinally (aDM: standardised beta=0.54, p<0.001; jDM: standardised beta=-0.70, p<0.001). Response to treatment in DM was associated with a decreasing SIGLEC1 (p<0.01, Wilcoxon test). SIGLEC1 was found upregulated in 8 of 19 patients with AS, 2 of 9 patients with IBM but not in IMNM. CONCLUSION: SIGLEC1 is a candidate biomarker to assess type I interferon activity in IIM and proved useful for monitoring disease activity and response to treatment in juvenile and adult DM.

Assessment of Hearing and Vestibular Functions in a Post-COVID-19 Patient: A Clinical Case Study.

SARS-CoV-2 infection may cause such complications as post-COVID-19 syndrome, which includes chronic fatigue, myalgia, arthralgia, as well as a variety of neurological manifestations, e.g., neuropathy of small fibers, hearing and vestibular dysfunction, and cognitive impairment. This clinical case describes a 41-year-old patient suffering from post-COVID-19 syndrome and chronic fatigue syndrome. A detailed examination was performed, including an in-depth study of peripheral and central hearing and vestibular functions, as well as small nerve fibers length and density in the skin and cornea of the eye. Contrary to expectations, no peripheral nervous system dysfunction was detected, despite the presence of dizziness and gait instability in the patient. Hearing tests (gap detection test and dichotic test) showed central auditory processing disorders. The evaluated lesion in the processing of temporal and verbal auditory information can be a significant factor contributing to additional overload of the neural activity and leading to chronic fatigue when performing daily activities in patients with CFS and post-COVID-19 complications.

Prevalence and epidemiological profile of celiac disease in children with type 1 diabetes mellitus: Experience from a tertiary care center of India.

BACKGROUND: The HLA associations of celiac disease (CD) in north Indians differ from that in Europeans. Our dietary gluten is among the highest in the world. Data on CD in people with diabetes (PWD) in north India is scant. OBJECTIVE: To estimate the prevalence and clinical profile of CD in children with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Retrospective review of case records of PWD with onset ≤18 years of age, registered between 2009 and 2020, having at least one anti tissue-transglutaminase (anti-tTG) serology report. RESULTS: Of 583 registered PWD, 398 (68.2%) had celiac serology screening. A positive report was obtained in 66 (16.6%). Of 51 biopsied people, 22 (5.5%) were diagnosed to have CD, 12 in the first 2 years of diabetes onset. Symptomatic CD at diagnosis was seen in 63% (14/22). Age at diabetes onset (median [IQR] age 5.5 years, [2-12]) was lower in PWD and CD compared to PWD alone (10 years, [7-14], p < 0.016). Of 36 biopsied children with anti-tTG >100 au/ml, 20 (55.5%) had CD, while 2 out of 15 (13.3%) of those with lower anti-tTG titer had histopathology suggestive of CD. Of 23 seropositive children not diagnosed with CD, 5 of 8 with anti tTG >100 au/ml, and all 15 with lower anti-tTG, had normalization of titers over the 24 (10-41) months. CONCLUSIONS: Our prevalence of CD is comparable to international data. Celiac disease was common with younger age at onset of T1D and higher titer of celiac serology. A high proportion was symptomatic of CD at diagnosis.

Assessment of Iodine and Selenium Nutritional Status in Women of Reproductive Age in Latvia.

Background and Objectives: Adequate dietary intake of iodine and selenium is essential during pregnancy. While iodine is vital for maternal thyroid function and fetal development, selenium contributes to the regulation of thyroid function and thyroid autoimmunity. This study aimed to assess the consumption of iodine- and selenium-containing products by women of reproductive age and the iodine and selenium nutritional status of pregnant women in Latvia. Materials and Methods: Population health survey (2010-2018) data were used to characterize dietary habits in women of reproductive age. Additionally, 129 pregnant women in the first trimester were recruited; they completed a questionnaire and were tested for thyroid function, urinary iodine concentration (UIC), and serum selenium and selenoprotein P levels. Results: The use of some dietary sources of iodine (e.g., milk and dairy products) and selenium (e.g., bread) has decreased in recent years. Less than 10% of respondents reported the use of iodized salt. The use of supplements has become more common (reported by almost 50% of respondents in 2018). Dietary habits were similar in pregnant women, but the use of supplements was even higher (almost 70%). Nevertheless, most supplements used in pregnancy had insufficient contents of iodine and selenium. Thyroid function was euthyreotic in all women, but 13.9% of participants had a thyroid peroxidase antibodies (TPO-ab) level above 60 IU/mL. The median UIC (IQR) was 147.2 (90.0-248.1) µg/gCr, and 52.8% of pregnant women had a UIC below 150 µg/gCr. The mean selenium (SD) level was 101.5 (35.6) µg/L; 30.1% of women had a selenium level below 80 µg/L. The median selenoprotein P level was 6.9 (3.1-9.0) mg/L. Conclusions: Iodine nutrition in Latvian population of pregnant women was near the lower limit of adequate and a third of the population had a selenium deficiency. Supplements were frequently used, but most did not contain the recommended amounts of iodine and selenium.

Health-care utilization and costs in adults with systemic lupus erythematosus in the United Kingdom: a real-world observational retrospective cohort analysis.

OBJECTIVE: The aim was to describe direct health-care costs for adults with SLE in the UK over time and by disease severity and encounter type. METHODS: Patients aged ≥18 years with SLE were identified using the linked Clinical Practice Research Datalink-Hospital Episode Statistics database from January 2005 to December 2017. Patients were classified as having mild, moderate or severe disease using an adapted claims-based algorithm based on prescriptions and co-morbid conditions. We estimated all-cause health-care costs and incremental costs associated with each year of follow-up compared with a baseline year, adjusting for age, sex, disease severity and co-morbid conditions (2017 UK pounds). RESULTS: We identified 802 patients; 369 (46.0%) with mild, 345 (43.0%) moderate and 88 (11.0%) severe disease. The mean all-cause cost increased in the 3 years before diagnosis, peaked in the first year after diagnosis and remained high. The adjusted total mean annual increase in costs per patient was £4476 (95% CI: £3809, £5143) greater in the year of diagnosis compared with the baseline year (P < 0.0001). The increase in costs per year was 4.7- and 1.6-fold higher among patients with severe SLE compared with those with mild and moderate SLE, respectively. Primary care utilization was the leading component of costs during the first year after diagnosis. CONCLUSION: The health-care costs for patients with SLE in the UK are substantial, remain high after diagnosis and increase with increasing severity. Future research should assess whether earlier diagnosis and treatment might reduce disease severity and associated high health-care costs.