Serum Autoantibodies Research Articles

Specific serum autoantibodies predict the development and progression of Alzheimer’s disease with high accuracy

Autoimmunity plays a key role in the pathogenesis of Alzheimer’s disease (AD). However, whether autoantibodies in peripheral blood can be used as biomarkers for AD has been elusive. Serum samples were obtained from 1,686 participants, including 767 with AD, 146 with mild cognitive impairment (MCI), 255 with other neurodegenerative diseases, and 518 healthy controls. Specific autoantibodies were measured using a custom-made immunoassay. Multivariate support vector machine models were employed to investigate the correlation between serum autoantibody levels and disease states. As a result, seven candidate AD-specific autoantibodies were identified, including MAPT, DNAJC8, KDM4D, SERF1A, CDKN1A, AGER, and ASXL1. A classification model with high accuracy (area under the curve (AUC) = 0.94) was established. Importantly, these autoantibodies could distinguish AD from other neurodegenerative diseases and out-performed amyloid and tau protein concentrations in cerebrospinal fluid in predicting cognitive decline (P < 0.001). This study indicated that AD onset and progression are possibly accompanied by an unappreciated serum autoantibody response. Therefore, future studies could optimize its application as a convenient biomarker for the early detection of AD.

Potential Significance of Serum Autoantibodies to Endometrial Antigens, α-Enolase and Hormones in Non-Invasive Diagnosis and Pathogenesis of Endometriosis.

The objective of the study was to evaluate the profile of serum autoantibodies and their diagnostic and pathogenetic significance in ovarian endometrioma (OEM) and deep infiltrative endometriosis (DIE). The study enrolled 74 patients with endometriosis (Group 1), including 53 patients with OEM (Subgroup 1a); 21 patients with DIE without ovarian lesions (Subgroup 1b); and 27 patients without endometriosis (Group 2). The diagnosis was confirmed by laparoscopic surgery and histologic examination of resected tissues. Antibodies (M, G) to tropomyosin 3 (TPM), tropomodulin 3 (TMOD), α-enolase (ENO), estradiol (E2), progesterone (PG), and human chorionic gonadotropin (hCG) were identified in blood serum using modified ELISA. In endometriosis, antibodies to endometrial antigens, hormones, and ENO were detected more often than antiphospholipid and antinuclear antibodies. Higher levels of IgM to TPM, hCG, E2, and PG and IgG to TMOD, ENO, E2, and hCG were found in Subgroup 1a compared to Group 2. IgM to TPM, hCG, E2, PG, and IgG to E2 and ENO had a high diagnostic value for OEM (AUC > 0.7), with antibodies to TPM having the highest sensitivity and specificity (73.6% and 81.5%). In Subgroup 1b, only the levels of IgM to TPM and hCG were higher than in Group 2. These antibodies had a high diagnostic value for DIE. Thus, endometriosis is associated with autoantibodies to endometrial antigens, α-enolase, steroid, and gonadotropic hormones. A wider spectrum of antibodies is detected in OEM than in DIE. These antibodies have a high diagnostic value for OEM and DIE and potential pathogenetic significance for endometriosis and associated infertility.

Autoantibody status, neuroradiological and clinical findings in children with acute cerebellitis

BackgroundAcute cerebellitis (AC) in children and adolescents is an inflammatory disease of the cerebellum due to viral or bacterial infections but also autoimmune-mediated processes. ObjectiveTo investigate the frequency of autoantibodies in serum and CSF as well as the neuroradiological features in children with AC. Material and methodsChildren presenting with symptoms suggestive of AC defined as acute/subacute onset of cerebellar symptoms and MRI evidence of cerebellar inflammation or additional CSF pleocytosis, positive oligoclonal bands (OCBs), and/or presence of autoantibodies in case of negative cerebellar MRI. Children fulfilling the above-mentioned criteria and a complete data set including clinical presentation, CSF studies, testing for neuronal/cerebellar and MOG antibodies as well as MRI scans performed at disease onset were eligible for this retrospective multicenter study. Results36 patients fulfilled the inclusion criteria for AC (f:m = 14:22, median age 5.5 years). Ataxia was the most common cerebellar symptom present in 30/36 (83 %) in addition to dysmetria (15/36) or dysarthria (13/36). A substantial number of children (21/36) also had signs of encephalitis such as somnolence or seizures. In 10/36 (28 %) children the following autoantibodies (abs) were found: MOG-abs (n = 5) in serum, GFAPα-abs (n = 1) in CSF, GlyR-abs (n = 1) in CSF, mGluR1-abs (n = 1) in CSF and serum. In two further children, antibodies were detected only in serum (GlyR-abs, n = 1; GFAPα-abs, n = 1). MRI signal alterations in cerebellum were found in 30/36 children (83 %). Additional supra- and/or infratentorial lesions were present in 12/36 children, including all five children with MOG-abs. Outcome after a median follow-up of 3 months (range: 1 a 75) was favorable with an mRS ≤2 in 24/36 (67 %) after therapy. Antibody (ab)-positive children were significantly more likely to have a better outcome than ab-negative children (p = .022). ConclusionIn nearly 30 % of children in our study with AC, a range of abs was found, underscoring that autoantibody testing in serum and CSF should be included in the work-up of a child with suspected AC. The detection of MOG-abs in AC does expand the MOGAD spectrum.

Tracking tumor alteration in glioma through serum fibroblast activation protein combined with image

PurposeDetecting tumor progression of glioma continues to pose a formidable challenge. The role of fibroblast activation protein (FAP) in gliomas has been demonstrated to facilitate tumor progression. Glioma-circulating biomarkers have not yet been used in clinical practice. This study seeks to evaluate the feasibility of glioma detection through the utilization of a serum FAP marker.MethodsWe adopted enzyme-linked immunosorbent assay (ELISA) technique to quantify the relative FAP level of serum autoantibodies in a cohort of 87 gliomas. The correlation between preoperative serum autoantibody relative FAP levels and postoperative pathology, including molecular pathology was investigated. A series of FAP tests were conducted on 33 cases of malignant gliomas in order to ascertain their efficacy in monitoring the progression of the disease in relation to imaging observations. To validate the presence of FAP expression in tumors, immunohistochemistry was conducted on four gliomas employing a FAP-specific antibody. Additionally, the investigation encompassed the correlation between postoperative tumor burden, as assessed through volumetric analysis, and the relative FAP level of serum autoantibodies.ResultsA considerable proportion of gliomas exhibited a significantly increased level of serum autoantibody relative FAP level. This elevation was closely associated with both histopathology and molecular pathology, and demonstrated longitudinal fluctuations and variations corresponding to the progression of the disease The correlation between the rise in serum autoantibody relative FAP level and tumor progression and/or exacerbation of symptoms was observed.ConclusionsThe measurement of serum autoantibody relative FAP level can be used to detect the disease as a valuable biomarker. The combined utilization of its detection alongside MR imaging has the potential to facilitate a more accurate and prompt diagnosis.

Relationship between Toll-like receptors and pathogenesis of Systemic Lupus Erythematosus

Systemic Lupus Erythematosus is a chronic inflammatory disease characterized by a loss of self-antigen tolerance and the development of high titers of serum autoantibodies, with a wide range of clinical manifestations and complex etiologies. Its etiology is influenced by various genetic, hormonal, immunologic, and environmental factors. SLE affects around 90% of women of reproductive age. The study aims to evaluate the serum levels of Toll-like receptor 7 (TLR7) in a sample of Iraqi SLE patients and its potential relationship with other clinical and laboratory parameters. The study included 100 female patients and 50 healthy females with an age range of (16-65) years old and healthy individuals with an age range of (16-65) years old and mean ages of (35.72 ±11.66 and 35.72 ±11.66) respectively. The current study is performed to estimate the serum levels of (TLR7, ANA, Urea, creatinine, and Vitamin D3) and a laboratory investigation for ESR, hemoglobin, and white blood cells by using the enzyme-linked immunosorbent assay (ELISA)and automated Fujifilm. Serum levels of TLR7 were increased in the SLE patients compared to the control, and a significant difference has been observed (P≤0.01) among SLE patients compared to the control. Urea, creatinine, and ESR were significantly higher. At the same time, the Vitamin D3, hemoglobin, and white blood cells were significantly lower (p&lt; 0.01) among SLE patients compared to control. On the other hand, there was no evidence of any correlation between TLR7 serum level and disease laboratory investigation. Keywords: Antinuclear autoantibody, Haemoglobin, Interferon, SLE, Toll-Like Receptor-7, WBC.

SAT155 Insulin Receptor Autoantibody Syndrome (Iras): A Rare Occurrence In Lymphoproliferative Disease

Abstract Disclosure: C. Villatoro Santos: None. E.A. Oral: None. Insulin receptor antibody syndrome (IRAS) may present as fasting hypoglycemia, high serum insulin, and serum autoantibodies to insulin receptor at low titers. We present a case of a patient with multiple myeloma (MM) who developed hypoglycemia suspected to be related to insulin receptor antibodies. The patient is a 60-year-old male with history of prediabetes, MM, anemia, and thrombocytopenia treated with carfilzomib, dexamethasone 20 mg weekly, and prior radiation to the right pelvis, who presented to the hospital for increased right hip pain and cough. Patient reported 4 days of markedly decreased appetite with poor intake. He noted increased chronic right hip and low back pain. On exam, he was cachectic, had hyperpigmentation under bilateral eyes, and muscle wasting. Hypoglycemia as low as 38 mg/dL (70-180 mg/dL) was noted. MM studies on hospital day 4 showed increased kappa-M protein and kappa-free light chains with worsening anemia and thrombocytopenia, concerning for progression of his disease. He later developed recurrent hypoglycemia; endocrinology was consulted on hospital day 6. He also had hyponatremia and borderline low blood pressure. Cortisol on hospital day 7 at 9:00 am was 15.4 μg/dL (5.3-22.5 μg/dL) in the setting of normoglycemia. On hospital day 9, hematology started dexamethasone 40 mg daily for 3 days for MM relapse, which resulted in marked improvement in his mental status, appetite, and resolution of hypoglycemia. On hospital day 11, he started weekly cyclophosphamide, bortezomib, plus dexamethasone for 3 weeks. Results for hypoglycemia workup returned on hospital day 12 from samples of Day 7: glucose 53 mg/dL (70-180 mg/dL), C-peptide 0.2 ng/mL (1-5.2 ng/mL), insulin 14.6 μU/mL (1-21 μU/mL), insulin antibodies undetectable, negative serum screen for oral hypoglycemic agents. His course was complicated by sepsis with gram-negative bacteremia treated with antibiotics and stress dose hydrocortisone. He was discharged to rehab on hospital day 34 on dexamethasone 4 mg daily. Glucose, c-peptide and insulin levels could be consistent with exogenous hyperinsulinemic hypoglycemia but may also represent delayed insulin clearance due to insulin receptor antibodies and autocrine suppression of pancreatic insulin production in a patient with no access to insulin. Therefore, the most likely diagnosis was IRAS. The insulin antibody radioactive essay was negative for native IgG and IgM antibodies; testing for insulin receptor antibodies is in progress as a clinical test is unavailable. Treatment is common with high doses of steroids. IRAs can be seen in patients with lymphoproliferative disorders and would respond to steroid treatment for hospital management. Definitive treatment should be tailored with oncology guidance. There is a need for an accessible clinical test for IRAS in the US. Presentation: Saturday, June 17, 2023

Comparison of circulating and excreted metals and of autoimmunity between two Great Plains Tribal communities

Metals contaminants of the environment from mine waste have been implicated as contributing agents in autoimmune disease. The current study compares metals and autoimmunity in two Tribal communities residing in the Black Hills and the Bighorn Mountains geographical regions that are scattered with extant hard rock mines. With documented drinking water contamination in both communities, in vivo levels of more than half of the measured serum and urine metals differed between the two communities and were substantially different from their national median values. Serum autoantibodies associated with systemic autoimmune disease were rare or at low-level, but antibodies to denatured (single-stranded) DNA and thyroid-specific autoantibodies were commonly elevated, especially in women. A three-tier statistical modeling process was carried out to examine individual metals exposure as predictors of autoantibody levels. For the most part only weak positive associations between individual metals and systemic autoantibodies were found, although univariate quantile regression analysis showed positive statistical associations of serum lead and antimony with anti-chromatin and anti-histone autoantibodies. Using age and gender-adjusted multivariable statistical models, metals did not predict anti-thyroglobulin or -thyroid peroxidase significantly and metals were generally negative predictors of the other autoantibodies. Overall these results suggest that elevated levels of environmental metals and metalloids in these communities may result in suppression of autoantibodies associated with systemic autoimmune disease.

B-078 Prevelance of Autoimmune Factors in Patients with Seizures of Unknown Etiology in Western China

Abstract Objective To delineate the features of autoantibody in patients with seizure of unknown etiology in Western China and to analyze other potential risk factors of an epileptic seizure. Methods From January 2017 to June 2022, 639 patients with unexplained seizure were assessed retrospectively. Neuronal autoantibodies were assessed in 471 individuals, including 12 common neural-specific autoantibodies, antibodies against four common pathogens associated with central nervous system infections, or neurophagocytosis, and two thyroid-related autoantibodies. Results Sixty-nine patients were positive for neural-specific autoantibodies in CSF and serum. Among the patients, 32 (46.38%) expressed NMDAR-Ab, 14 (20.29%) expressed GABABR-Ab, 10 (14.49%) expressed LGI1-Ab, 7 (10.14%) expressed GFAP-Ab, 3 (4.34%) expressed Yo-Ab, 2 (2.90%) expressed CASP2-Ab, and 1 (1.45%) expressed Hu-Ab. Compared to patients with non-autoimmune epileptic seizure, the positive rates of thyroid-related antibody expression and the neurophagocytosis pathogen levels of HSV-IgG and T. gondii-IgG were significantly different in patients with autoimmune epileptic seizure. Conclusion This study elucidated the antibody status of autoimmune epilepsy in western China, allowing for better identification and diagnosis of autoimmune epilepsy in the future.

B-113 Diagnostic Value of Autoantibodies against D-3-phosphoglycerate Dehydrogenase (PGDH) among Patients with Liver Diseases

Abstract Background We determined serum autoantibodies against D-3-phosphoglycerate dehydrogenase (anti-PGDH) in patients with liver diseases using a well-validated line immunoblot assay, and analysed their diagnostic significance. Methods The studied panel comprised serum samples from 383 patients with the following liver diseases: 87 autoimmune hepatitis (AIH), 88 primary biliary cholangitis (PBC), 76 chronic hepatitis B, 79 hepatitis C, 53 drug-induced liver injury as well as sera from 69 patients with autoimmune diseases (systemic lupus erythematosus or rheumatoid arthritis) and 30 healthy blood donors. The line immunoblot EUROLINE Autoimmune Liver Diseases 14 Ag (EUROIMMUN) was used to test for anti-PGDH. The intensities of the bands were automatically evaluated using the EUROLineScan software (EUROIMMUN). Indirect immunofluorescence was used to detect other autoantibodies, including anti-nuclear autoantibodies (ANA) and anti-smooth muscle antibodies (ASMA). Results The prevalence of anti-PGDH was 18.3% across all patients with liver diseases (36.8% in AIH; 10.2% in PBC), 1.5% in patients with autoimmune diseases, and 3.3% in blood donors. ANA but not ASMA were detectable in all anti-PGDH positive patients with liver diseases. Patients with anti-PGDH displayed no significant differences in age, liver function, IgG serum level and ANA patterns compared to those without anti-PGDH. Anti-PGDH positivity was observed at various stages of liver disease, including acute and chronic liver injury, liver cirrhosis, and liver cancer. Conclusion The anti-PGDH prevalence in AIH patients was highest among patients with liver or autoimmune diseases. Presence of anti-PGDH seems to be a specific marker for AIH and may support the diagnosis of AIH.

Effects of autoimmune abnormalities on skeletal muscle regeneration after needle puncture in mice.

Regeneration of injured skeletal muscles is supported by the activation of satellite cells, and excessive traumatic injuries may trigger abnormal processes, such as fibrosis. Because the participation of immune cells is crucial during skeletal muscle repair, systemic autoimmune diseases impair their regeneration. This study focused on a traumatic injury by injection and investigated the effect of autoimmune diseases on skeletal muscle regeneration. Male mice of MRL/MpJ-Faslpr/lpr and MRL/MpJ (6-7 months old) were used for autoimmune disease and healthy groups. The abdominal walls punctured by a needle were histologically analyzed at 1, 3, and 8 days postinjection. In both groups, injured skeletal muscle tissues showed necrosis and inflammatory cell infiltrations on day 1, increased cell density at 3 days, and regenerative myotubes with central nuclei without fibrosis at 8 days. Gr-1+ neutrophils at injured skeletal muscle were abundant at 1 day, and then substantially decreased starting from 3 days in both groups. The number of CD3+ T cells was remarkably higher in MRL/MpJ-Faslpr/lpr than that in MRL/MpJ at 1 day, and a similar tendency was observed in B220+ B cells. The numbers of IBA1+ macrophages and bromodeoxyuridine-incorporating cells tended to be higher at 3 days, and those of the latter, mainly proliferating paired-box-7+ satellite cells, showed significance at other time points and negatively correlated with the autoimmune disease indices, such as spleen weights or serum autoantibody level. Thus, this result suggested that injured skeletal muscle by minor trauma is normally regenerated regardless of the effects of autoimmune diseases, although lymphocyte infiltrations during these processes were more severe in MRL/MpJ-Faslpr/lpr.

Serum autoantibody profiling of oral squamous cell carcinoma patients reveals NUBP2 as a potential diagnostic marker.

Oral Squamous Cell Carcinoma (OSCC), a common malignancy of the head and neck region, is frequently diagnosed at advanced stages, necessitating the development of efficient diagnostic methods. Profiling autoantibodies generated against tumor-associated antigens have lately demonstrated a promising role in diagnosis, predicting disease course, and response to therapeutics and relapse. In the current study, we, for the first time, aimed to identify and evaluate the diagnostic value of autoantibodies in serum samples of patients with OSCC using autoantibody profiling by an immunome protein array. The utility of anti-NUBP2 antibody and tissue positivity in OSCC was further evaluated. We identified a total of 53 autoantibodies with significant differential levels between OSCC and control groups, including 25 that were increased in OSCC and 28 that were decreased. These included autoantibodies against Thymidine kinase 1 (TK1), nucleotide-binding protein 2 (NUBP2), and protein pyrroline-5-carboxylate reductase 1 (PYCR1), among others. Immunohistochemical validation indicated positive staining of NUBP2 in a large majority of cases (72%). Further, analysis of OSCC data available in TCGA revealed higher NUBP2 expression correlated with better disease-free patient survival. In conclusion, the differential serum autoantibodies identified in the current study, including those for NUBP2, could be used as potential biomarkers for early diagnosis or as screening biomarkers for OSCC pending investigation in a larger cohort.

Hydrophobicity and molecular mass-based separation method for autoantibody discovery from mammalian total cellular proteins.

Serum autoantibody profiles are unique to individuals and reflect the level and history of autoimmunity and tumor immunity. The identification of autoantibody biomarkers is critical for the development of immune monitoring systems for immune-related disorders. Here, we present a practical method for large-scale autoantibody discovery using total cellular proteins from cultured mammalian cells. We found that nucleic acid-free and fully denatured water-soluble total cellular proteins from mammalian cells were superior, allowing precise separation by reversed-phase HPLC after preparing a large set of homogeneous total cellular proteins. After separating the proteins based on hydrophobicity, the fractionated samples were subjected to molecular mass analysis using conventional SDS-PAGE. The resulting two-dimensional gel electrophoresis was successfully employed for immune blotting and LC-MS/MS analysis. All procedures, including TRIzol-based total cellular protein extraction, solubilization of denatured proteins, reversed-phase HPLC separation, and SDS-PAGE, were highly reproducible and easily scalable. We propose this novel two-dimensional gel electrophoresis system as an alternative proteomics-based methodology suitable for large-scale autoantibody discovery.

Proteomic aptamer analysis reveals serum biomarkers associated with disease mechanisms and phenotypes of systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease that affects multiple organs, leading to elevated morbidity and mortality with limited treatment options. The early detection of organ involvement is challenging as there is currently no serum marker available to predict the progression of SSc. The aptamer technology proteomic analysis holds the potential to correlate SSc manifestations with serum proteins up to femtomolar concentrations. This is a two-tier study of serum samples from women with SSc (including patients with interstitial lung disease - ILD - at high-resolution CT scan) and age-matched healthy controls (HC) that were first analyzed with aptamer-based proteomic analysis for over 1300 proteins. Proposed associated proteins were validated by ELISA first in an independent cohort of patients with SSc and HC, and selected proteins subject to further validation in two additional cohorts. The preliminary aptamer-based proteomic analysis identified 33 proteins with significantly different concentrations in SSc compared to HC sera and 9 associated with SSc-ILD, including proteins involved in extracellular matrix formation and cell-cell adhesion, angiogenesis, leukocyte recruitment, activation, and signaling. Further validations in independent cohorts ultimately confirmed the association of specific proteins with early SSc onset, specific organ involvement, and serum autoantibodies. Our multi-tier proteomic analysis identified serum proteins discriminating patients with SSc and HC or associated with different SSc subsets, disease duration, and manifestations, including ILD, skin involvement, esophageal disease, and autoantibodies.

Редкие иммуноопосредованные нежелательные явления. Клинический случай синдрома Шегрена на фоне иммунотерапии у пациента с аденокарциномой легкого

Given the rapid expansion of indications for immune checkpoint inhibitors therapy in the clinical practice of oncologists, as well as the emergence of new drugs with similar mechanisms of action, knowledge of rare immune-related adverse events is extremely important for physicians, both in terms of their early detection and optimisation of treatment tactics. Despite their rarity, the spectrum of rheumatological manifestations is quite broad, which requires the continued detailed accumulation and analysis of clinical material. The present clinical observation convincingly demonstrates that when prescribing immune checkpoint inhibitors in case of symptoms suspicious of Sjögren's syndrome, a thorough history and a complete examination, including specialized diagnostic tests to evaluate salivary and lacrimal gland function, should be performed. The differential diagnosis of Sjögren's syndrome with other nosologies requires serum autoantibody testing and salivary gland biopsy. Prompt referral of the patient to a rheumatologist is critical, to avoid delay in making a correct diagnosis. Early diagnosis and timely treatment of toxic reactions are the key to successful anti-tumour therapy. Achieving this goal requires close collaboration between multidisciplinary physicians, the patient, and the patient's family.

Anti-Ro52 positivity is associated with progressive interstitial lung disease in systemic sclerosis—an exploratory study

BackgroundInterstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc). Prognostic biomarkers are needed to identify SSc-ILD patients at risk for progressive pulmonary fibrosis. This study investigates autoantibodies measured in bronchoalveolar lavage (BAL) fluid and in serum in reference to the clinical disease course of SSc-ILD.MethodsFifteen patients with new onset SSc-ILD underwent bronchoscopy. Autoantibody levels were analyzed using addressable laser bead immunoassay from BAL fluid and the serum. In a separate longitudinal cohort of 43 patients with early SSc-ILD, autoantibodies in serum were measured at baseline and pulmonary function tests were performed at least 2 times over the course of at least 2 or more years. Linear mixed effect models were created to investigate the relationship between specific autoantibodies and progression of SSc-ILD. Finally, lung tissue from healthy controls and from subjects with SSc was analyzed for the presence of the Ro52 antigen using immunohistochemistry.ResultsAmong SSc-ILD patients who were positive for anti-Ro52 (N = 5), 3 (60%) had enrichment of anti-Ro52 in BAL fluid at a ratio exceeding 50x. In the longitudinal cohort, 10/43 patients (23%) were anti-Ro52 positive and 16/43 (37%) were anti-scl-70 positive. Presence of anti-Scl-70 was associated with a lower vital capacity (VC) at baseline (-12.6% predicted VC [%pVC]; 95%CI: -25.0, -0.29; p = 0.045), but was not significantly associated with loss of lung function over time (-1.07%pVC/year; 95%CI: -2.86, 0.71; p = 0.230). The presence of anti-Ro52 was significantly associated with the loss of lung function over time (-2.41%pVC/year; 95% CI: -4.28, -0.54; p = 0.013). Rate of loss of lung function increased linearly with increasing anti-Ro52 antibody levels (-0.03%pVC per arbitrary units/mL and year; 95%CI: -0.05, -0.02; p < 0.001). Immunohistochemical staining localized the Ro52 antigen to alveolar M2 macrophages in peripheral lung tissue both in subjects with and without SSc.ConclusionsThis study suggests that antibodies targeting Ro52 are enriched in the lungs of patients with new-onset SSc-ILD, linking Ro52 autoimmunity to the pulmonary pathology of SSc. Clinical and immunohistochemical data corroborates these findings and suggest that anti-Ro52 may serve as a potential biomarker of progressive SSc-ILD.

Recommendations for the diagnosis and treatment of Sjögren's syndrome in China

Sjögren's syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocyte proliferation and progressive exocrine gland damage. In addition to the impairment of salivary and lacrimal gland function, SS can present with multi-system and multi-organ involvement, accompanied by autoantibodies in serum and hyperimmunoglobulinemia. SS can be divided into primary and secondary forms based on the absence or presence, respectively, of concurrent connective tissue diseases such as systemic lupus erythematosus and rheumatoid arthritis. Based on evidence and guidelines from China and other countries, the Chinese Rheumatology Association drafted standardized criteria for the diagnosis and treatment of primary SS. The objectives were to standardize the detection and interpretation of key indicators for the diagnosis of SS, including serum anti-SSA antibody and labial gland pathology, suggest the use of the widely accepted European League Against Rheumatism (EULAR)-SS disease activity index for the evaluation of the disease, and standardize the rational management of SS patients with topical and systemic therapies.

Сравнение профиля сывороточных аутоантител у женщин при разных формах эндометриоза

Сравнение профиля сывороточных аутоантител у женщин при разных формах эндометриоза

Association of anti-Ro52 antibody with depression and anxiety in patients with connective tissue diseases: an observational, single-centre, cross-sectional study.

To explore the risk factors of anxiety and depression, especially their association with serum autoantibodies, in patients with connective tissue diseases (CTDs). Three hundred and fifty-two inpatients with CTDs were recruited and their demographic, serological and imaging data were collected through the medical record system. Depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) respectively. Analysis of variance (ANOVA), rank sum test, chi-square test and logistic regression were performed to investigate risk factors for depression and anxiety. The prevalence of depression (PHQ-9 ≥ 5) and anxiety (GAD-7 ≥5) in CTD patients was significantly higher than that in the Chinese general population (depression: 44.3% vs. 32.2%, anxiety: 39.5% vs. 22.2%). Sleep time was a protective factor for both depression and anxiety (OR=0.734, 95% CI: 0.616~0.874, p<0.001 and OR=0.684, 95% CI: 0.559~0.835, P<0.001, respectively) while anti-Ro52 antibody was a risk factor for them (OR=5.466, 95% CI: 2.978~10.032, p<0.001 and OR=4.075, 95% CI: 2.073~8.010, p<0.001, respectively). Further analysis showed that anti-Ro52 antibody was a risk factor for depression and anxiety in all four subgroups, namely SLE, SS, RA, and other CTDs. Anti-Ro52 antibody is probably a risk factor for depression and anxiety in patients with connective tissue diseases. CTD patients with the presence of anti-Ro52 antibody are more prone to depression and anxiety than those without it.

Treatable Traits in Systemic Sclerosis.

Systemic sclerosis (SSc) is a chronic systemic disease within the spectrum of connective tissue diseases, specifically characterized by vascular abnormalities and inflammatory and fibrotic involvement of the skin and internal organs resulting in high morbidity and mortality. The clinical phenotype of SSc is heterogeneous, and serum autoantibodies together with the extent of skin involvement have a predictive value in the risk stratification. Current recommendations include an organ-based management according to the predominant involvement with only limited individual factors included in the treatment algorithm. Similar to what has been proposed for other chronic diseases, we hypothesize that a "treatable trait" approach based on relevant phenotypes and endotypes could address the unmet needs in SSc stratification and treatment to maximize the outcomes. We provide herein a comprehensive review and a critical discussion of the literature regarding potential treatable traits in SSc, focusing on established and candidate biomarkers, with the purpose of setting the bases for a precision medicine-based approach. The discussion, structured based on the organ involvement, allows to conjugate the pathogenetic mechanisms of tissue injury with the proposed predictors, particularly autoantibodies and other serum biomarkers. Ultimately, we are convinced that precision medicine is the ideal guide to manage a complex condition such as SSc for which available treatments are largely unsatisfactory.

High-throughput autoantibody profiling of different stages of Schistosomiasis japonica

Infection by the Schistosoma japonicum can result in acute, chronic and late-stage manifestations. The latter often presents with severe organ failures and premature death. Importantly, infection can also produce autoimmune phenomena reflected by the development of autoantibodies. We wished to explore and profile the presence of autoantibodies in sera of patients with different stages of S. japonicum infection with the added aim of providing a reference assisting diagnosis. Blood samples from 55 patients with chronic and 20 patients with late-stage schistosomiasis japonica together, with a control group of 50 healthy people were randomly investigated against a microarray of 121 different autoantigens. In addition, the frequency of antibodies against Schistosoma egg antigen (SEA) was examined. In the sera from patients with chronic schistosomiasis japonica, 14 different highly expressed autoantibodies were detected, while patients with late-stage schistosomiasis were found to express as many as 43 autoantibody specificities together with a significantly higher frequency of antibodies against SEA compared to the control group. The findings presented suggest that autoantibody-based classification of schistosomiasis japonica represents a promising approach for the elucidation of subtypes of the disease. This approach may reflect differential disease mechanisms, which could ultimately lead to better treatment.