[High anti-topoisomerase-1 autoantibodies levels are associated with the extension of skin fibrosis and vascular progression in patients with systemic sclerosis]. / Des taux élevés d'auto-anticorps anti-topo-isomérase-1 sont associés à l'extension de la fibrose cutanée et à la progression vasculaire chez les patients atteints de sclérodermie systémique.

BACKGROUND: Anti-centromere antibodies, anti-topoisomerase-1 antibodies (ATA), and anti-RNA-polymerase III antibodies are three Systemic Sclerosis (SSc)-specific autoantibodies. Their detection is helpful in determining the prognosis. We aimed to evaluate whether ATA levels were associated with disease severity at diagnosis or disease progression during follow-up in ATA positive patients. METHODS: We conducted a single-centre French retrospective observational study, between 2014 and 2021. ATA positive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc with a minimal follow-up of 1 year and 2 ATA dosages were included. SSc patients with high IgG ATA levels at baseline (>240IU/mL) were compared with SSc patients with low levels (≤240IU/mL), at inclusion and at 1 and 3 years. A variation of at least 30 % of ATA levels was considered significant. RESULTS: Fifty-nine SSc patients were included and analysed. There was a predominance of women and of patients with diffuse interstitial lung disease. Patients with high ATA levels exhibited a higher skin sclerosis assessed by the modified Rodnan skin score (P=0.0480). They had a lower carbon monoxide transfer coefficient (P=0.0457), a lower forced vital capacity (FVC) (P=0.0427) and more frequently had a FVC under 80 %, when compared to patients with low ATA levels (P=0.0423). Initial high ATA levels were associated with vascular progression at one year (21.95 % vs. 0 %; P=0.0495). CONCLUSION: ATA levels are associated with skin sclerosis and vascular progression in SSc. Beyond the detection of ATA, quantifying this autoantibody might be of interest in predicting disease severity and prognosis in SSc.

Thyroid Inflammation and Immunity During the COVID-19 Pandemic: A Comprehensive Review and Case Study.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the development of various vaccines. Reports have emerged suggesting a possible association between SARS-CoV-2 vaccination and the onset of thyroid diseases. This review explores the clinical aspects of thyroid disorders following SARS-CoV-2 vaccination, including a case report of a patient with concomitant subacute thyroiditis (SAT) and Graves' disease (GD) with blocking thyrotropin receptor autoantibodies (TSH-R-Ab) following SARS-CoV-2 vaccination. SAT, characterized by transient inflammation of the thyroid gland, has been reported after SARS-CoV-2 vaccination. GD, an autoimmune hyperthyroidism, has also been observed post-vaccination, often with stimulating TSH-R-Ab. Graves' orbitopathy (GO) has been associated with SARS-CoV-2 vaccination in patients with a history of immune thyroid disease. The unique case underscores a very rare thyroid condition of functional hypothyroidism in possible relation to SARS-CoV-2 vaccination and the usefulness of functional analysis of TSH-R-Ab that can provide valuable insights into disease pathogenesis and help to guide treatment. This review highlights the need for continued monitoring and awareness of potential thyroid-related complications following SARS-CoV-2 vaccination.

Anti-Gephyrin Antibodies: A Novel Specificity in Patients With Systemic Sclerosis and Lower Bowel Dysfunction.

OBJECTIVE: Autoantibodies are clinically useful in phenotyping patients with systemic sclerosis (SSc). Gastrointestinal (GI) function is regulated by the enteric nervous system (ENS) and commonly impaired in SSc, suggesting that the SSc autoimmune response may target ENS antigens. We sought to identify novel anti-ENS autoantibodies with an aim to clinically phenotype SSc GI dysfunction. METHODS: Serum from a patient with SSc with GI dysfunction but without defined SSc-associated autoantibodies was used for autoantibody discovery. Immunoprecipitations performed with murine myenteric plexus lysates were on-bead digested, and autoantigens were identified by mass spectrometry. Prevalence was determined, and clinical features associated with novel autoantibodies were evaluated in a SSc cohort using regression analyses. The expression of gephyrin in human GI tract tissue was examined by immunohistochemistry. RESULTS: We identified gephyrin as a novel SSc autoantigen. Anti-gephyrin antibodies were present in 9% of patients with SSc (16/188) and absent in healthy controls (0/46). Anti-gephyrin antibody-positive patients had higher constipation scores (1.00 vs 0.50, P = 0.02) and were more likely to have severe constipation and severe distention/bloating (46% vs 15%, P = 0.005; 54% vs 25%, P = 0.023, respectively). Anti-gephyrin antibody levels were significantly higher among patients with severe constipation (0.04 vs 0.00; P = 0.001) and severe distention and bloating (0.03 vs 0.004; P = 0.010). Severe constipation was associated with anti-gephyrin antibodies even in the adjusted model. Importantly, gephyrin was expressed in the ENS, which regulates gut motility. CONCLUSION: Gephyrin is a novel ENS autoantigen that is expressed in human myenteric ganglia. Anti-gephyrin autoantibodies are associated with the presence and severity of constipation in patients with SSc.

TSH receptor autoantibody levels post-total thyroidectomy in Graves' ophthalmopathy: a meta-analysis.

BACKGROUND: TSH receptor autoantibodies (TRAbs) are pathognomonic for Graves' disease and are thought to also underly the pathogenesis of Graves' ophthalmopathy (GO). A decline in TRAb levels has been documented post-total thyroidectomy (TTx) in GO, however with conflicting correlations with disease outcomes. The aim of the study was to compare the effectiveness of TTx to other treatment modalities of Graves' disease and examine whether the lowering of TRAbs is associated with GO improvements. METHOD: We searched electronic databases including Medline, Embase, Scopus, and Web of Science until 31 September 2022 using a broad range of keywords. Patients with GO undergoing TTx with measurements of both TRAbs and progression of the disease using a validated GO scoring system were included. Fourteen studies encompassing data from 1047 patients with GO met our eligibility criteria. The PRISMA guidelines were followed, and five studies had comparable data that were suitable for a meta-analysis. RESULTS: The Cochrane Risk of Bias tool for RCTs showed low risk of bias across most domains. The pooled odds ratio showed that more patients significantly had normalized TRAb levels post-TTx as compared to other interventions (OR: 1.36, 95% CI: 1.02-1.81, p = 0.035). But, there was no significant difference in GO improvement post-TTx as compared with other intervention groups. CONCLUSIONS: This meta-analysis shows that TRAb levels may decline largely post-TTx, but may not predict added improvements to the progression of GO. Thus, future studies with uniform designs are required to assess the minimal significant GO improvements.

Antibodies Associated With Autoimmune Encephalitis in Patients With Presumed Neurodegenerative Dementia.

BACKGROUND & OBJECTIVES: Autoimmune encephalitis (AIE) may present with prominent cognitive disturbances without overt inflammatory changes in MRI and CSF. Identification of these neurodegenerative dementia diagnosis mimics is important because patients generally respond to immunotherapy. The objective of this study was to determine the frequency of neuronal antibodies in patients with presumed neurodegenerative dementia and describe the clinical characteristics of the patients with neuronal antibodies. METHODS: In this retrospective cohort study, 920 patients were included with neurodegenerative dementia diagnosis from established cohorts at 2 large Dutch academic memory clinics. In total, 1,398 samples were tested (both CSF and serum in 478 patients) using immunohistochemistry (IHC), cell-based assays (CBA), and live hippocampal cell cultures (LN). To ascertain specificity and prevent false positive results, samples had to test positive by at least 2 different research techniques. Clinical data were retrieved from patient files. RESULTS: Neuronal antibodies were detected in 7 patients (0.8%), including anti-IgLON5 (n = 3), anti-LGI1 (n = 2), anti-DPPX, and anti-NMDAR. Clinical symptoms atypical for neurodegenerative diseases were identified in all 7 and included subacute deterioration (n = 3), myoclonus (n = 2), a history of autoimmune disease (n = 2), a fluctuating disease course (n = 1), and epileptic seizures (n = 1). In this cohort, no patients with antibodies fulfilled the criteria for rapidly progressive dementia (RPD), yet a subacute deterioration was reported in 3 patients later in the disease course. Brain MRI of none of the patients demonstrated abnormalities suggestive for AIE. CSF pleocytosis was found in 1 patient, considered as an atypical sign for neurodegenerative diseases. Compared with patients without neuronal antibodies (4 per antibody-positive patient), atypical clinical signs for neurodegenerative diseases were seen more frequently among the patients with antibodies (100% vs 21%, p = 0.0003), especially a subacute deterioration or fluctuating course (57% vs 7%, p = 0.009). DISCUSSION: A small, but clinically relevant proportion of patients suspected to have neurodegenerative dementias have neuronal antibodies indicative of AIE and might benefit from immunotherapy. In patients with atypical signs for neurodegenerative diseases, clinicians should consider neuronal antibody testing. Physicians should keep in mind the clinical phenotype and confirmation of positive test results to avoid false positive results and administration of potential harmful therapy for the wrong indication.

Antinuclear antibodies in individuals with COVID-19 reflect underlying disease: Identification of new autoantibodies in systemic sclerosis (CDK9) and malignancy (RNF20, RCC1, TRIP13).

A high prevalence of antinuclear antibodies (ANA) in COVID-19 has been insinuated, but the nature of the target antigens is poorly understood. We studied ANA by indirect immunofluorescence in 229 individuals with COVID-19. The target antigens of high titer ANA (≥1:320) were determined by immunoprecipitation (IP) combined with liquid-chromatography-mass spectrometry (MS). High titer ANA (≥1:320) were found in 14 (6%) of the individuals with COVID-19. Of the 14 COVID-19 cases with high titer ANA, 6 had an underlying autoimmune disease and 5 a malignancy. IP-MS revealed known target antigens associated with autoimmune disease as well as novel autoantigens, including CDK9 (in systemic sclerosis) and RNF20, RCC1 and TRIP13 (in malignancy). The novel autoantigens were confirmed by IP-Western blotting. In conclusion, in depth analysis of the targets of high titer ANA revealed novel autoantigens in systemic sclerosis and in malignant disease.

Anti-kelchlike protein 11 antibody-associated encephalitis: Two case reports and review of the literature.

BACKGROUND AND PURPOSE: Kelchlike protein 11 antibodies (KLHL11-IgGs) were first described in 2019 as a marker of paraneoplastic neurological syndromes (PNSs). They have mostly been associated with testicular germ cell tumors (tGCTs). METHODS: Two patients with KLHL11-IgG encephalitis are reported, and the literature is comprehensively reviewed. RESULTS: Patient 1 had been in remission from a tGCT 10 years prior. He developed episodic vertigo and diplopia progressing over a few days. Treatment with corticosteroids (CSs) was started a few days after symptom onset. Patient 2 had transient diplopia, which resolved spontaneously. Visual problems persisted for 7 months, when he additionally developed a progressive cerebellar syndrome. One year after onset, CS treatment was started. Initial magnetic resonance imaging was unremarkable in both patients, but analysis of cerebrospinal fluid (CSF) revealed chronic inflammation. KLHL11-IgG was positive in both patients (Patient 1 only in CSF, Patient 2 in serum). Neoplastic screening has so far not revealed any signs of active underlying malignancy. We found 15 publications of 112 patients in total with KLHL11-IgG encephalitis. Most patients (n = 82) had a cerebellar syndrome with or without signs of rhombencephalitis. The most common symptoms were ataxia (n = 82) and vertigo (n = 47), followed by oculomotor disturbances (n = 35) and hearing disorders (n = 31). Eighty of 84 patients had a GCT as an underlying tumor. CONCLUSIONS: Our cases demonstrate classical symptoms of KLHL11-IgG encephalitis. Early diagnosis and therapy are imperative. As with other PNSs, clinical awareness is needed and further studies are required especially in regard to therapeutic management.

Identification of salivary autoantibodies as biomarkers of oral cancer with immunoglobulin A enrichment combined with affinity mass spectrometry.

Globally, oral cavity squamous cell carcinoma (OSCC) is one of the most common fatal illnesses. Its high mortality is ascribed to the fact that the disease is often diagnosed at a late stage, which indicates an urgent need for approaches for the early detection of OSCC. The use of salivary autoantibodies (autoAbs) as OSCC biomarkers has numerous advantages such as easy access to saliva samples and efficient detection of autoAbs using well-established secondary reagents. To improve OSCC screening, we identified OSCC-associated autoAbs with the enrichment of salivary autoAbs combined with affinity mass spectrometry (MS). The salivary IgA of healthy individuals and OSCC patients was purified with peptide M-conjugated beads and then applied to immunoprecipitated antigens (Ags) in OSCC cells. Using tandem MS analysis and spectral counting-based quantitation, the level of 10 Ags increased in the OSCC group compared with the control group. Moreover, salivary levels of autoAbs to the 10 Ags were determined by a multiplexed bead-based immunoassay. Among them, seven were significantly higher in early-stage OSCC patients than in healthy individuals. A marker panel consisting of autoAbs to LMAN2, PTGR1, RAB13, and UQCRC2 was further developed to improve the early diagnosis of OSCC.

Applications of Peptide Microarrays in Autoantibody, Infection, and Cancer Detection.

The diversity of the antigen-specific humoral immune response reflects the interaction of the immune system with pathogens and autoantigens. Peptide microarray analysis opens up new perspectives for the use of antibodies as diagnostic biomarkers and provides unique access to a more differentiated view on humoral responses to disease. This review focuses on the latest applications of peptide microarrays for the serologic medical diagnosis of autoimmunity, infectious diseases (including COVID-19), and cancer.

Stratifying risk for onset of type 1 diabetes using islet autoantibody trajectory clustering.

AIMS/HYPOTHESIS: Islet autoantibodies can be detected prior to the onset of type 1 diabetes and are important tools for aetiologic studies, prevention trials and disease screening. Current risk stratification models rely on the positivity status of islet autoantibodies alone, but additional autoantibody characteristics may be important for understanding disease onset. This work aimed to determine if a data-driven model incorporating characteristics of islet autoantibody development, including timing, type and titre, could stratify risk for type 1 diabetes onset. METHODS: Data on autoantibodies against GAD (GADA), tyrosine phosphatase islet antigen-2 (IA-2A) and insulin (IAA) were obtained for 1,415 children enrolled in The Environmental Determinants of Diabetes in the Young study with at least one positive autoantibody measurement from years 1 to 12 of life. Unsupervised machine learning algorithms were trained to identify clusters of autoantibody development based on islet autoantibody timing, type and titre. Risk for type 1 diabetes across each identified cluster was evaluated using time-to-event analysis. RESULTS: We identified 2-4 clusters in each year cohort that differed by autoantibody timing, titre and type. During the first 3 years of life, risk for type 1 diabetes onset was driven by membership in clusters with high titres of all three autoantibodies (1-year risk: 20.87-56.25%, 5-year risk: 67.73-69.19%). Type 1 diabetes risk transitioned to type-specific titres during ages 4 to 8, as clusters with high titres of IA-2A (1-year risk: 20.88-28.93%, 5-year risk: 62.73-78.78%) showed faster progression to diabetes compared with high titres of GADA (1-year risk: 4.38-6.11%, 5-year risk: 25.06-31.44%). The importance of high GADA titres decreased during ages 9 to 12, with clusters containing high titres of IA-2A alone (1-year risk: 14.82-30.93%) or both GADA and IA-2A (1-year risk: 8.27-25.00%) demonstrating increased risk. CONCLUSIONS/INTERPRETATION: This unsupervised machine learning approach provides a novel tool for stratifying risk for type 1 diabetes onset using multiple autoantibody characteristics. These findings suggest that age-dependent changes in IA-2A titres modulate risk for type 1 diabetes onset across 12 years of life. Overall, this work supports incorporation of islet autoantibody timing, type and titre in risk stratification models for aetiologic studies, prevention trials and disease screening.

ANA-specific antibodies, ANA patterns, anti-ds-DNA results, and clinical diagnosis: a laboratory and clinical audit.

The diagnosis of systemic autoimmune diseases (SAID) is challenging, due to overlapping features with other non-immune disorders. Anti-nuclear antibodies (ANA)/anti-cellular antibodies are the sensitive screening tests but anti-double-stranded-deoxyribonucleic acid-antibody (anti-ds-DNA) and ANA-specific antibodies are specific for SAID. We aimed to look at ANA-specific antibodies in our patients and correlated them with ANA patterns, anti-ds-DNA, and clinical diagnosis for proper interpretation and better patient management cost-effectively. A retrospective data analysis of 641 patients was done (1st of February 2019 to 31st of July 2021) who were tested for ANA-specific antibodies at the Immunology Department of Indus Hospital and Health Network. ANA and anti-ds-DNA results and clinical diagnosis were also analyzed for ANA-specific antibody-positive patients. Descriptive data were presented in mean ± standard deviation and frequency percentages whereas inferential data were analyzed with a chi-square test for association between ANA-specific antibodies status, ANA, anti-ds-DNA, and clinical features. ANA-specific antibodies test revealed positivity for at least one autoantibody in 245 (38.2%) patients. Of these, ANA was tested in 206 patients reactive for ANA-specific antibodies and found positive in 195 (95%) as compared to negative (< 0.001). Speckled and homogenous were predominant ANA patterns in ANA-specific antibody-positives (56% and 42% respectively). Multiple ANA patterns were found in 18 patients most commonly with systemic lupus erythematosus (SLE) and mixed connective tissue disorder (MCTD). Anti-SSA were the most common ANA-specific antibodies (50%) and were mostly found in sera with speckled (61/97) and homogenous (38/97) patterns and associated mostly with SLE (48%) and Sjogren's syndrome (86%). Among ANA-negative patients, anti-SSA were the most common antibodies (n = 5). Anti-ds-DNA was found in 66% of SLE patients along with another ANA-specific antibody. This study showed that testing for ANA-specific antibodies cannot be gated on ANA patterns. Also, there is a redundancy of these antibodies with various clinical diagnoses. Moreover, they are useful in making a diagnosis in ANA-negative patients as well with clinical suspicion.

Dysregulation of secondary bile acid metabolism precedes islet autoimmunity and type 1 diabetes.

The gut microbiota is crucial in the regulation of bile acid (BA) metabolism. However, not much is known about the regulation of BAs during progression to type 1 diabetes (T1D). Here, we analyzed serum and stool BAs in longitudinal samples collected at 3, 6, 12, 18, 24, and 36 months of age from children who developed a single islet autoantibody (AAb) (P1Ab; n = 23) or multiple islet AAbs (P2Ab; n = 13) and controls (CTRs; n = 38) who remained AAb negative. We also analyzed the stool microbiome in a subgroup of these children. Factor analysis showed that age had the strongest impact on both BA and microbiome profiles. We found that at an early age, systemic BAs and microbial secondary BA pathways were altered in the P2Ab group compared with the P1Ab and CTR groups. Our findings thus suggest that dysregulated BA metabolism in early life may contribute to the risk and pathogenesis of T1D.

[Clinical significance of autoantibodies against ubiquitin carboxyl hydrolase L1 epitopes in the screening and diagnosis of Sjögren syndrome].

Objective: To study the clinical significance of autoantibodies against different ubiquitin carboxyl hydrolase L1 (UCH-L1) epitopes in Sjogren syndrome (SS). Methods: The serum levels of different UCH-L1 epitope autoantibodies in 98 SS patients [SS group, 17 males and 81 females, aged (49.1±12.3) years] in the Fifth Affiliated Hospital of Zhengzhou University and Peking University People's Hospital from January 2017 to January 2020 and 37 healthy controls [control group, 6 males and 31 females, aged (46.3±5.8) years] were determined by enzyme-linked immunosorbent assay (ELISA). Three potential epitopes of UCH-L1 protein were analyzed and synthesized and anti-UCH-L1203-214 and anti-UCH-L158-69 antibodies were studied between the two groups. The levels of the two anti-UCH-L1 antibodies in the two groups were compared. The correlation between the levels of UCH-L1 antibodies and clinical data of SS patients were analyzed by Pearson correlation analysis. Results: The serum levels of anti-UCH-L1203-214 and anti-UCH-L158-69 antibody in SS patients were significantly higher than those in healthy controls (HCs) (anti-UCH-L1203-214: 108.2±54.3 vs 78.9±25.8, P<0.001, anti-UCH-L158-69: 86.8±33.3 vs 60.4±21.5, P<0.001). The positive rates of anti-UCH-L1203-214 and anti-UCH-L158-69 antibodies in serums of SS patients were 27.6 % (27/98) and 25.5% (25/98), and those in HCs were 2.7%(1/37) and 5.4 %(2/37), respectively. In SS patients with positive serum anti-UCH-L158-69 antibody, the levels of IgG, γ globulin and rheumatoid factor (RF) and anti-SS-related antigen B (anti-SSB) antibody positive rate were all significantly higher than those in patients with negative antibody (all P<0.05). In SS patients with negative antinuclear antibody (ANA), anti-RNA binding protein (anti-RNP) antibody, anti-SS-related antigen A (anti-SSA) antibody and anti-SSB antibody, the positive rates of anti-UCH-L1203-214 antibody was 32.1%(9/28), 27.2%(25/92), 36.4%(12/33), 28.6%(18/63), respectively; and the positive rates of anti-UCH-L158-69 antibody was 21.4%(6/28), 30.4%(28/92), 30.3%(10/33), 20.6%(13/63), respectively. The level of serum anti-UCH-L1203-214 antibody in SS patients was positively correlated with the IgA level (r=0.21, P=0.024). The level of anti-UCH-L158-69 antibody in SS patients was positively correlated with the levels of γ-globulin, IgG and RF (r=0.35, 0.33, 0.32, all P<0.01). Conclusion: Autoantibodies against UCH-L1 epitopes are correlated with some clinical parameters of SS patients, which is of promising significance in the screening and diagnosis of SS.

Brief Report - Monoclonal Antibodies Illustrate the Difficulties in Measuring Blocking TSH Receptor Antibodies.

TSH receptor (TSHR) antibodies are the cause of Graves' disease and may also be found in patients with Hashimoto's thyroiditis. They come in at least three varieties: thyroid stimulating, thyroid blocking and neutral. The measurement of TSH receptor antibodies in Graves' disease and Hashimoto's thyroiditis is a common clinical activity and can be useful in diagnosis and prognosis. We show that it is not possible to detect the blocking variety of TSHR antibody in patients with Graves' disease because the stimulating antibody may overwhelm the measurement of blocking in the bioassays available for their measurement and may blind the valid interpretation of the results. To help explain this in more detail we show a series of studies with monoclonal TSHR antibodies which support this conclusion.

Analysis of Risk Factors for Rheumatoid Arthritis in Yunnan: A Small-Scale Case-Control Study.

Objective: To study the risk factors of rheumatoid arthritis (RA) in Yunnan and provide reference for its clinical prevention and treatment. Methods: From January 2014 to February 2022, a total of 249 RA patients who were admitted to the First People's Hospital of Yunnan Province were selected and 149 healthy people were selected as the controls. The medical records, clinical data of blood test results of anticyclic citrullinated polypeptide (anti-CCP) antibody, antikeratin antibody (AKA), and antiperinuclear factor (APF) were collected. Logistic regression and receiver operating curve (ROC) were used to analyze the correlation between blood anti-CCP antibody, AKA, and APF and the occurrence of RA. Results: Univariate analysis showed that the age, proportion of hypertension, and diabetes patients in RA patients were significantly different from those in the control group (p < 0.05), but there was no statistical difference in sex (p > 0.05). The area under the curve (AUC) of the serum anti-CCP antibody level in the diagnosis of RA was 0.76 (95% CI: 0.72-0.81, p < 0.01), the sensitivity was 85.23%, the specificity was 61.45%, and the cutoff value was 18.07AU/mL. The positive rates of AKA (33.73%) and APF (43.37%) in the RA patients were significantly higher than those in the controls (4.03% and 6.04%), and the differences were statistically significant (p < 0.001). After adjusting for age, sex, hypertension, and diabetes, logistic regression analysis showed that anti-CCP positivity, AKA positive, and APF positive were all independent risk factors for RA (OR = 20.24, 95% CI: 9.36-43.77, p < 0.01; OR = 4.33, 95% CI: 1.62-11.60, p < 0.01; OR = 5.28, 95% CI: 2.33-11.99, p < 0.01). Conclusion: Anti-CCP positive, AKA positive, and APF positive are independent risk factors for the occurrence of RA. Serum anti-CCP level has high sensitivity but low specificity in the diagnosis of RA.

Autoantibodies to Tumor Necrosis Factor in Patients with Active Pulmonary Tuberculosis.

BACKGROUND: Tumor necrosis factor (TNF) plays an important role in immune responses to the causative agent of tuberculosis, Mycobacterium tuberculosis. Additionally, TNF can also mediate many negative disease manifestations. The aim of this study was to assess the contribution of anti-TNF autoantibodies to the pathogenesis of active pulmonary tuberculosis (TB). METHODS: The levels of anti-TNF autoantibody classes and subclasses were determined by applying enzyme-linked immunosorbent assays (ELISAs). The levels of TNF and of its soluble receptors were also evaluated using commercial ELISA kits. RESULTS: The levels of both types of soluble TNF receptors were lower patients with TB than in healthy donors. Patients with TB had higher titers of immunoglobulin (Ig)G class and IgG3 subclass anti-TNF autoantibodies in comparison with healthy donors. Patients who had a disseminated TB infection had higher TNF level and IgG, IgG1 and IgG3 autoantibody titers compared with patients who had a localized TB infection. CONCLUSIONS: Changes in the titers of anti-TNF autoantibody classes and subclasses were noted in patients with TB, suggesting their possible contribution to the disease pathogenesis of TB.

Anti-tissue transglutaminase (tTG) screening using relative light units to identify IgA deficiency.

IgA deficiency is more common in patients with coeliac disease (CD). Total IgA levels are often recommended as part of first line coeliac testing along with anti-tissue transglutaminase (tTG) IgA, to identify these patients and reduce falsely negative results. This study aimed to identify patients with complete IgA deficiency by determining a cut-off threshold on chemiluminescent tTG IgA testing. A chemiluminescent assay QUANTA Flash h-tTG was reviewed using the BIO-FLASH automated platform. tTG relative light units (RLU) were analysed in relation to total IgA levels. Correlation analysis was performed and distributions of tTG RLU were compared between the IgA deficient and IgA detectable groups, and ROC analysis was performed to identify a suitable threshold. A total of 203 samples were reviewed in our initial cohort. There was a strong correlation between IgA and tTG RLU levels (Pearson correlation coefficient 0.495, p<0.001). There was a statistically significant difference of 170.57 RLU between the means of the IgA deficient and IgA detectable group (p<0.001, 156.50-184.64). A receiver operating characteristic (ROC) curve was generated with area under the curve of 0.997. A cut-off of less than 300 tTG RLU for identification of IgA deficiency was chosen, which had a sensitivity and specificity of 100% and 98.9%, respectively. A prospective validation cohort was conducted which confirmed the initial results. Our study has validated an algorithm to identify complete IgA deficiency by implementing a threshold of 300 RLU during tTG IgA testing by chemiluminescent immunoassay. This approach resulted in a sensitivity of 100% to detect patients with complete IgA deficiency. Widespread uptake would result in improved workflow, workload and turnaround time, and reduce the need for unnecessary blanket testing of total IgA in the screening for coeliac disease.

Clinical Application Value of High-Frequency Ultrasound Combined with Detection of Serum High Mobility Group Box 1, Soluble IL-2 Receptor, and Thyroglobulin Antibody in Diagnosing Thyroid Cancer.

Objective: The aim of this study is to explore the clinical application value of high-frequency ultrasound combined with detection of serum high mobility group box (HMGB-1), soluble IL-2 receptor (SIL-2R), and thyroglobulin antibody (TgAb) in diagnosing thyroid cancer. Methods: By means of retrospective study, 50 thyroid cancer patients treated in our hospital from January 2019 to January 2021 were selected as the thyroid cancer group, 50 patients with benign thyroid lesions were included in the benign lesion group, and 50 healthy individuals examined in our hospital in the same period were included in the control group. All study objects received high-frequency ultrasound examination, and at the same time, their serum HMGB-1, SIL-2R, and TgAb levels were measured. After that, the results of high-frequency ultrasound examination were analyzed, the diagnostic efficacy of different diagnosis methods was explored, and receiver operating characteristic (ROC) curves were plotted. Results: According to the results of high-frequency ultrasound examination, there were significant differences in echogenicity surrounding and inside the lesion, calcification, blood flow distribution, and blood flow parameters between the thyroid cancer group and the benign lesion group (P < 0.001); the HMGB-1, SIL-2R, and TgAb levels were statistically different among the three groups (P < 0.001), and the level values of HMGB-1, SIL-2R, and TgAb of the thyroid cancer group were, respectively, (12.26 ± 1.32) ng/ml, (108.65 ± 9.75) pmol/L, and (690.65 ± 34.47) IU/mL; the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of high-frequency ultrasound combined with detection of serum HMGB-1, SIL-2R, and TgAb were, respectively, 98.0%, 95.0%, 90.7%, and 99.0%, and AUC (95%CI) = 0.965 (0.931-0.999). Conclusion: High-frequency ultrasound combined with detection of serum HMGB-1, SIL-2R, and TgAb has a good value in diagnosing thyroid cancer, which should be promoted in practice.