Clinical significance of the anti-Nucleolar Organizer Region 90 antibodies (NOR90) in systemic sclerosis: Analysis of the European Scleroderma Trials and Research (EUSTAR) cohort and a systematic literature review.

BACKGROUND: The anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) reported in systemic sclerosis (SSc). Especially due to low prevalence, the clinical relevance of NOR90 in SSc remains uncertain. OBJECTIVES: To analyze the clinical associations of NOR90 in patients with SSc in a multicentric cohort. METHODS: Post-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) database, with additional information on NOR90. Further, we performed a systematic literature search, using the terms "systemic sclerosis" and "NOR90" across three databases: Medline via PubMed, Scopus, and Thomson Reuters' Web of Science Core Collection, from inception to November 1st, 2023. RESULTS: Overall, 1318 patients with SSc were included (mean age 58.3 ± 13.7 years, 81.3 % female), of whom 44 (3.3 %) were positive for NOR90. Of these, 32 were also positive for one of the SSc-criteria antibodies: 9/44 (20.5 %) for anti-topoisomerase I, 18/42 (42.9 %) for anti-centromere, and 5/40 (12.5 %) for anti-RNA polymerase III. NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal (GI) symptoms compared to NOR90-negative patients. In multivariable analysis, NOR90 remained significantly associated with lower mRSS and less frequent GI symptoms. The literature search identified 17 articles, including a total number of 87 NOR90-positive out of 3357 SSc patients, corresponding to an overall prevalence of 2.6 %. CONCLUSION: To our best knowledge, this is the largest SSc cohort tested for NOR90 to date, confirming the NOR90 prevalence in SSc patients is around 3 %.

Identifying antinuclear antibody positive individuals at risk for developing systemic autoimmune disease: development and validation of a real-time risk model.

Objective: Positive antinuclear antibodies (ANAs) cause diagnostic dilemmas for clinicians. Currently, no tools exist to help clinicians interpret the significance of a positive ANA in individuals without diagnosed autoimmune diseases. We developed and validated a risk model to predict risk of developing autoimmune disease in positive ANA individuals. Methods: Using a de-identified electronic health record (EHR), we randomly chart reviewed 2,000 positive ANA individuals to determine if a systemic autoimmune disease was diagnosed by a rheumatologist. A priori, we considered demographics, billing codes for autoimmune disease-related symptoms, and laboratory values as variables for the risk model. We performed logistic regression and machine learning models using training and validation samples. Results: We assembled training (n = 1030) and validation (n = 449) sets. Positive ANA individuals who were younger, female, had a higher titer ANA, higher platelet count, disease-specific autoantibodies, and more billing codes related to symptoms of autoimmune diseases were all more likely to develop autoimmune diseases. The most important variables included having a disease-specific autoantibody, number of billing codes for autoimmune disease-related symptoms, and platelet count. In the logistic regression model, AUC was 0.83 (95% CI 0.79-0.86) in the training set and 0.75 (95% CI 0.68-0.81) in the validation set. Conclusion: We developed and validated a risk model that predicts risk for developing systemic autoimmune diseases and can be deployed easily within the EHR. The model can risk stratify positive ANA individuals to ensure high-risk individuals receive urgent rheumatology referrals while reassuring low-risk individuals and reducing unnecessary referrals.

Saline Breast Implant Associated With Inflammatory Arthritis and Positive Antinuclear Antibodies (ANA): A Case Report.

Breast implants, whether silicone or saline-filled, have a silicone shell and have been used for decades. Studies have shown an association between silicon with systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, and vasculitis. However, controversy and inconsistency have been pervasive in the literature with respect to the role of breast implants in the development of autoimmune diseases. A 39-year-old female with a past medical history of breast cancer and a family history of Sjogren's syndrome was referred to rheumatology for positive antinuclear antibodies (ANA) and polyarthralgia. She received textured saline breast implants for post-mastectomy reconstruction and subsequently developed fatigue, bilateral joint pain in her hands, wrists, and feet, and swelling in her fingers with prolonged morning stiffness, unintentional weight loss, and dry eyes. Physical examination revealed mild swelling of the bilateral metacarpophalangeal (MCP), proximal interphalangeal joint (PIP,) and distal interphalangeal (DIP) joints, and difficulty making a fist. Laboratory workup revealed a normal complete blood count (CBC) and comprehensive metabolic panel (CMP) with slight elevations in inflammatory markers. Autoimmune workup revealed positive ANA 1:640 (nucleolar) and 1:160 (speckled), positive U1RNP, and RNA polymerase III with negative SSA/SSB/dsDNA and Scl-70 Ab. Following elective implant removal after nationwide recall for heightened cancer risk, many of her symptoms spontaneously resolved. The clinical case of inflammatory arthritis with positive ANA antibodies following saline breast implants highlights the importance of considering the possible health implications of silicone from a rheumatologic perspective. This case demonstrates that it may be reasonable that an association exists, and further research on a large scale would be valuable.

Systemic lupus erythematosus associated with erythema multiforme: A rare case report of Rowell's syndrome.

Key Clinical Message: Although it is very uncommon, SLE may initially present with recurrent episodes of EM-like rash. Despite the various possibilities underlying their association, prompt identification, and treatment of SLE in patients presenting with EM is important to prevent death or serious organ damage. Abstract: Rowell's syndrome (RS) is an uncommon presentation of systemic lupus erythematosus (SLE) with erythema multiforme (EM)-like lesions associated with specific serological changes, including positive rheumatoid factor (RF), speckled antinuclear antibody (ANA), positive rheumatoid factor, or anti-La antibodies in the serum. Our case, a 41-year-old male, presented with features of EM. Upon investigation, we identified underlying systemic lupus erythematosus, marking a rare instance of SLE presenting for the first time as EM. Classical or true EM is precipitated by trigger factors such as infective agents like the herpes simplex virus, Mycoplasma pneumoniae, drugs like anticonvulsants, antibiotics, and non-steroid anti-inflammatory drugs, any underlying malignancy, or connective tissue disorders, and is not associated with any specific serological abnormalities. EM cases associated with LE lesions where an EM trigger factor is missing are considered an RS diagnostic criterion. In this case report, the importance of considering SLE in patients presenting initially with recurrent episodes of EM-like rash is emphasized. RS should be considered, especially when there is no evidence of triggering factors. Early diagnosis and prompt treatment of SLE are crucial to preventing death and irreversible organ damage.

The Binding Properties of Antibodies to Z-DNA in the Sera of Normal Healthy Subjects.

Antibodies to DNA are a diverse set of antibodies that bind sites on DNA, a polymeric macromolecule that displays various conformations. In a previous study, we showed that sera of normal healthy subjects (NHS) contain IgG antibodies to Z-DNA, a left-handed helix with a zig-zig backbone. Recent studies have demonstrated the presence of Z-DNA in bacterial biofilms, suggesting a source of this conformation to induce responses. To characterize further antibodies to Z-DNA, we used an ELISA assay with brominated poly(dGdC) as a source of Z-DNA and determined the isotype of these antibodies and their binding properties. Results of these studies indicate that NHS sera contain IgM and IgA as well as IgG anti-Z-DNA antibodies. As shown by the effects of ionic strength in association and dissociation assays, the anti-Z-DNA antibodies bind primarily by electrostatic interactions; this type of binding differs from that of induced anti-Z-DNA antibodies from immunized animals which bind by non-ionic interactions. Furthermore, urea caused dissociation of NHS anti-Z-DNA at molar concentrations much lower than those for the induced antibodies. These studies also showed IgA anti-Z-DNA antibodies in fecal water. Together, these studies demonstrate that antibodies to Z-DNA occur commonly in normal immunity and may arise as a response to Z-DNA of bacterial origin.

Effectiveness of Chemotherapy on Long-Term Survival in a Case of Advanced Juvenile Hepatocellular Carcinoma Without Viral Hepatitis Infection.

Hepatocellular carcinoma (HCC) usually occurs in settings of cirrhosis and chronic hepatitis B or C virus (HBV and HCV, respectively) infection; it is extremely rare in patients <40 years of age since viral- or alcohol-induced chronic hepatitis develops over a prolonged period. Juvenile HCC is mostly associated with persistent HBV infection; cases unrelated to HBV or HCV infection (non-B, non-C juvenile HCC) are sporadic and treated in the same way as classical HCC. A woman in her late 30s was diagnosed with HCC in a healthy liver; her imaging findings were typical of HCC with bone metastasis. She was administered a combination of tyrosine kinase inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors. Throughout chemotherapy, the liver reserve was Grade A on the Child-Pugh classification and tumor markers remained under control without marked elevation. Our patient is the first reported long-term survivor of unresectable non-B, non-C juvenile HCC following chemotherapeutic treatment.

New-onset autoimmune disease after COVID-19.

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may trigger autoimmune disease (AD) through initial innate immune activation with subsequent aberrations in adaptive immune cells leading to AD. While there are multiple reports of incident AD diagnosed after COVID-19, the risk in the context of key circulating strains is unknown. Methods: TriNetX, a global, federated, health research network providing access to electronic medical records across 74 healthcare organizations, was utilized to define an adult cohort between January 1, 2020, and March 3, 2023. Exposure was defined as COVID-19 diagnosis (ICD-10 code or positive laboratory test). Age- and sex-propensity score-matched controls never had COVID-19 diagnosed. Outcomes were assessed 1 month to 1 year after the index date. Patients with AD prior to or within 1 month after the index date were excluded from the primary analysis. Incidence and risk ratios of each AD were assessed. Results: A total of 3,908,592 patients were included. Of 24 AD patients assessed, adjusted risk ratios for eight AD patients who had COVID-19 were higher compared to those who had no COVID-19. Cutaneous vasculitis (adjusted hazard ratio (aHR): 1.82; 95% CI 1.55-2.13), polyarteritis nodosa (aHR: 1.76; 95% CI 1.15-2.70), and hypersensitivity angiitis (aHR: 1.64; 95% CI 1.12-2.38) had the highest risk ratios. Overall, psoriasis (0.15%), rheumatoid arthritis (0.14%), and type 1 diabetes (0.13%) had the highest incidence during the study period, and of these, psoriasis and diabetes were more likely after COVID-19. The risk of any AD was lower if COVID-19 was diagnosed when Omicron variants were the predominant circulating strains. A positive antinuclear antibody was more likely and predictive of AD after COVID-19. Discussion: SARS-CoV-2 may be a potential trigger for some AD, but the risk for AD may decrease with time given the apparent lower risk after infection with Omicron variants.

Clinical and serological characterization of acute pleuropericarditis suggests an autoinflammatory pathogenesis and highlights risk factors for recurrent attacks.

PURPOSE: We describe the manifestations and course of patients with pleuropericarditis (PP). Serum parameters were analyzed to evaluate the contribution of autoimmune and autoinflammatory mechanisms to PP pathogenesis. Finally, we outline risk factors for recurrent PP attacks. METHODS: Electronic medical records of the University Hospital Heidelberg were screened for PP diagnosis between the years 2009 and 2021. A total of 164 patients were detected and compared to patients suffering from systemic lupus erythematosus (SLE)-associated PP. Follow-up data were collected until January 2023. RESULTS: In 57.3% of a total of 164 PP cases, no trigger was identified (idiopathic PP). The clinical manifestations were similar in subgroups with different triggers (idiopathic, post-cardiac injury and post-infectious). None of the patients in the idiopathic-PP (i-PP) group fulfilled the diagnostic criteria of an autoimmune disease and the i-PP group could be clearly discriminated by clinical, epidemiological and serological means from the control cohort of SLE-associated PP. After a median follow-up of 1048 days, the majority of PP patients (72.7%) had at least one PP relapse. Univariate analyses showed that CRP, SAA (serum amyloid A), troponin T, NT-BNP and post-cardiac injury were negatively correlated, while the presence of fever and an idiopathic trigger were positively correlated with recurrence of PP. Multivariate analyses showed that fever, an idiopathic trigger and low SAA values were risk factors for PP recurrence. CONCLUSION: This study highlights that most cases of PP are idiopathic and PP cases with various triggers have an identical clinical phenotype. Our data suggest that the clinical, epidemiological and serological characteristics of idiopathic PP considerably differ from patients with PP caused by autoimmune disease like SLE. We further demonstrate that PP has a high risk of recurrence and identify factors associated with this risk, allowing for a targeted secondary prophylaxis.

Comprehensive Exploration of Antinuclear Antibodies (ANAs): Unveiling Clinical Significance, Associations with Cancer, and the Nuances of Differential Diagnosis in Positive ANA Patients.

This comprehensive review delves into the complex realm of antinuclear antibodies (ANAs), expanding beyond their traditional involvement in autoimmune rheumatic disorders. By digging into historical changes, diagnostic complexity, and clinical significance, the debate reveals the shifting relationships between ANAs, particularly with cancer. Specialized studies provide practical insights on ANA testing processes, standardization, and upcoming challenges. Examining prevalence trends in the United States provides a time dimension to ANA dynamics, linking autoimmune and oncological considerations. The debate delves into the complexity of lupus erythematosus, emphasizing ANAs' diverse presentations and their potential as flexible diagnostic and prognostic indicators. The complex relationship between ANAs and cancer is highlighted, demonstrating their potential as early markers or indicators of malignancies. Looking ahead, this synthesis anticipates advances in personalized medicine and collaborative research, putting ANAs at the forefront of advanced diagnostics and treatments for autoimmune disorders and cancer. This synthesis envisions a future for ANA research in which these antibodies play a critical role in promoting personalized treatment, enhancing diagnostics, and fostering collaborative initiatives that cross traditional boundaries. As ANAs grow more prominent at the junction of autoimmune illnesses and cancer, this synthesis lays the path for further research and novel advances in understanding, diagnosing, and treating complicated medical conditions.

T Lymphocyte Interferon-gamma Response to Anaplasmataceae-related Major Surface Proteins and Ankyrin A in Fibromyalgia.

BACKGROUND: The aetiology of fibromyalgia is unknown; its symptoms may be related to a T-lymphocyte-mediated response to infectious organisms. OBJECTIVES: First, to test the hypothesis that fibromyalgia is associated with increased interferon (IFN)-γ-secreting T-lymphocytes after stimulation with Anaplasmataceae-related major surface proteins (MSFs) and the macromolecular translocation type IV secretion system effector ankyrin repeat domain-containing protein A (AnkA). Second, to ascertain the relationship in fibromyalgia between (i) the IFN-γ-secreting T-lymphocyte response to stimulation with Anaplasmataceae-related MSFs and AnkA, and (ii) co-infection by Borrelia and Yersinia spp., and antinuclear antibodies. METHODS: Using a case-control design, patients fulfilling the American College of Rheumatology revised criteria for fibromyalgia, and controls, underwent the following blinded assessments: (i) enzyme- linked immune absorbent spot (ELISpot) IFN-γ release assay of T-lymphocyte reactivity to Anaplasmataceae-related MSFs and AnkA; (ii) ELISpot IFN-γ release assays of T-lymphocyte reactivity to three Borrelia antigens, namely Borrelia burgdorferi full antigen (B31); peptide mix (from Borrelia burgdorferi sensu stricto, Borrelia afzelii, Borrelia garinii); and Borrelia burgdorferi lymphocyte function-associated antigen-1; (iii) immunoglobulin (Ig) A assay by enzyme-linked immunosorbent assay (ELISA) of antibodies to Yersinia spp.; (iv) IgG (ELISA) antibodies to Yersinia spp.; (v) serum antinuclear antibodies (immunofluorescence). RESULTS: The groups were age- and sex-matched. The mean (standard error) value of IFN-γ release for the fibromyalgia group was 1.52 (0.26), compared with 1.00 (0.22) for the controls. Generalised linear modelling (p<0.001) of IFN-γ release in the fibromyalgia patients showed significant main effects of all three indices of Borrelia infection and of antinuclear antibodies. CONCLUSION: Anaplasmataceae may play an aetiological role in fibromyalgia.

Recognition of rare antinuclear antibody patterns based on a novel attention-based enhancement framework.

Rare antinuclear antibody (ANA) pattern recognition has been a widely applied technology for routine ANA screening in clinical laboratories. In recent years, the application of deep learning methods in recognizing ANA patterns has witnessed remarkable advancements. However, the majority of studies in this field have primarily focused on the classification of the most common ANA patterns, while another subset has concentrated on the detection of mitotic metaphase cells. To date, no prior research has been specifically dedicated to the identification of rare ANA patterns. In the present paper, we introduce a novel attention-based enhancement framework, which was designed for the recognition of rare ANA patterns in ANA-indirect immunofluorescence images. More specifically, we selected the algorithm with the best performance as our target detection network by conducting comparative experiments. We then further developed and enhanced the chosen algorithm through a series of optimizations. Then, attention mechanism was introduced to facilitate neural networks in expediting the learning process, extracting more essential and distinctive features for the target features that belong to the specific patterns. The proposed approach has helped to obtained high precision rate of 86.40%, 82.75% recall, 84.24% F1 score and 84.64% mean average precision for a 9-category rare ANA pattern detection task on our dataset. Finally, we evaluated the potential of the model as medical technologist assistant and observed that the technologist's performance improved after referring to the results of the model prediction. These promising results highlighted its potential as an efficient and reliable tool to assist medical technologists in their clinical practice.

Naomi Rothfield, MD, MACR: A Giant Gift in a Small Package.

Naomi Rothfield was truly a pied piper of lupus. She had an abiding interest in the characterization and clinical significance of antinuclear antibodies and anti-DNA antibodies in the serum of systemic lupus erythematosus (SLE) patients. She described the use of serum complement in SLE diagnosis and the association of inherited complement deficiencies with SLE. Under her leadership, numerous professionals focused their clinical and research activities to benefit lupus patients. Naomi was also instrumental in establishing a lupus group to assist lupus patients, which became one of the founding chapters of the Lupus Foundation of America.

Hydrolysis of Oligodeoxyribonucleotides on the Microarray Surface and in Solution by Catalytic Anti-DNA Antibodies in Systemic Lupus Erythematosus.

Anti-DNA antibodies are known to be classical serological hallmarks of systemic lupus erythematosus (SLE). In addition to high-affinity antibodies, the autoantibody pool also contains natural catalytic anti-DNA antibodies that recognize and hydrolyze DNA. However, the specificity of such antibodies is uncertain. In addition, DNA binding to a surface such as the cell membrane, can also affect its recognition by antibodies. Here, we analyzed the hydrolysis of short oligodeoxyribonucleotides (ODNs) immobilized on the microarray surface and in solution by catalytic anti-DNA antibodies from SLE patients. It has been shown that IgG antibodies from SLE patients hydrolyze ODNs more effectively both in solution and on the surface, compared to IgG from healthy individuals. The data obtained indicate a more efficient hydrolysis of ODNs in solution than immobilized ODNs on the surface. In addition, differences in the specificity of recognition and hydrolysis of certain ODNs by anti-DNA antibodies were revealed, indicating the formation of autoantibodies to specific DNA motifs in SLE. The data obtained expand our understanding of the role of anti-DNA antibodies in SLE. Differences in the recognition and hydrolysis of surface-tethered and dissolved ODNs need to be considered in DNA microarray applications.

Neurosarcoidosis: inicio con compromiso de múltiples sitios neurológicos / Neurosarcoidosis: Onset with involvement of multiple neurological sites

Resumen Presentamos el caso de una mujer joven sana, que consultó por parálisis facial periférica izquierda asociada a fiebre, tos seca, disnea y astenia de dos semanas de evolución. Al examen físico se evidenció hipoestesia en dermatomas D6 a D12 izquierdos y galactorrea bi lateral. En el laboratorio presentaba serologías virales negativas, eritrosedimentación, títulos de anticuerpos antinucleares, prolactina y hormona tiroestimulante elevados, con anticuerpos antiperoxidasa positivos. La tomografía computarizada mostró múltiples adenopatías cervicales, mediastinales e hiliares bilaterales, sin com promiso del parénquima pulmonar. El cultivo de líquido cefalorraquídeo fue negativo para gérmenes comunes, micobacterias (Xpert MTB/RIF), y la citología no mostró atipia. Se realizó una resonancia magnética con con traste endovenoso de cerebro sin hallazgos patológicos y de columna con alteración de la señal centromedular de D6 a D9 de casi la totalidad del espesor del cordón, con refuerzo con contraste endovenoso. Durante la in ternación recuperó la sensibilidad en tronco izquierdo y no repitió episodios febriles o tusígenos. Se realizó mediastinoscopía con biopsia ganglionar con anatomía patológica con presencia de numerosos granulomas no caseificantes compatibles con sarcoidosis. Se clasificó como neurosarcoidosis probable e inició tratamiento con corticoides con mejoría de los síntomas neurológi cos restantes, realizándose una resonancia magnética a los tres meses, donde la alteración de la señal se limitaba desde D7 a D8. Nuestro objetivo es destacar la presentación neurológica en múltiples sitios que obligó a descartar otras entidades más frecuentes, así como la evolución favorable incluso previo al inicio de un esquema de tratamiento de primera línea.

Abstract We present the case of a healthy young woman who consulted for left peripheral facial palsy associated with fever, dry cough, dyspnea, and asthenia of two weeks' evolution. Physical examination revealed hypoesthesia in left T6 to T12 dermatomes and bilateral galactorrhea. In the laboratory, she presented negative viral serology, elevated erythrocyte sedimentation rate, antinuclear an tibody titers, prolactin and thyroid-stimulating hormone, with positive antiperoxidase antibodies. Computed to mography showed multiple bilateral cervical, mediastinal, and hilar adenopathies, without involvement of lung parenchyma. Cerebrospinal fluid culture was negative for common germs, mycobacteria, and Xpert MTB/RIF, and cytology did not show atypia. Contrast-enhanced magnetic resonance was performed on the brain without pathological findings and on the spine with alteration of the centromedullary signal from T6 to T9 of almost the entire thickness of the cord, with posterior enhancement with gadolinium. During hospitalization, she recovered sensitivity in the left trunk and did not repeat febrile or cough episodes. She was referred to another center for mediastinoscopy with lymph node biopsy revealing the presence of numerous non-caseating granulomas compatible with sarcoidosis. It was classified as probable neurosarcoidosis and started treatment with corticoste roids with improvement of the remaining neurological symptoms. A magnetic resonance was performed three months later where the signal alteration was limited from T7 to T8. Our objective is to highlight the florid neu rological presentation that made it necessary to rule out other more frequent entities and the favorable evolution even before starting a first-line scheme of treatment.

Antinuclear Antibodies Are Associated with an Increased Risk of Diffuse Large B-Cell Lymphoma.

Immune dysregulation is thought to increase the risk of non-Hodgkin lymphoma (NHL), but the evidence varies by subtype. We evaluated whether antinuclear antibodies (ANA), double-stranded DNA antibodies (anti-dsDNA), and extractable nuclear antigen antibodies (anti-ENA) were associated with the risk of common NHL subtypes in a nested case-control study. The autoantibodies were tested in serum collected years prior to NHL diagnosis in 832 cases and 809 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (95% CI) for the association with NHL risk. No association was observed between ANA positivity and NHL risk overall (OR: 1.18, 95% CI: 0.88-1.58); however, ANA positivity was associated with an increased risk of diffuse large B-cell lymphoma (DLBCL) (OR: 1.83, 95% CI: 1.15-2.91), with 19.7% of cases and 12.2% of controls testing positive. The presence of either anti-ENA or anti-dsDNA was associated with an increased risk of NHL (OR: 2.93, 95% CI: 1.18-7.28), particularly DLBCL (OR: 3.51, 95% CI: 1.02-12.0) and marginal zone lymphoma (OR: 8.86, 95% CI: 1.26-62.0). Our study demonstrates that autoantibodies are associated with an elevated risk of DLBCL, providing support for autoimmunity as a risk factor.

Clinical features and visual prognosis of very late-onset neuromyelitis optica spectrum disorder-related optic neuritis.

BACKGROUND: Very late-onset neuromyelitis optica spectrum disorder-related optic neuritis is limited to a few case reports. OBJECTIVE: To investigate the clinical features and visual prognosis of very late-onset neuromyelitis optica spectrum disorder-related optic neuritis. METHODS: This study evaluated 22 patients with first-onset optic neuritis and fulfilled the 2015 diagnosis criteria for neuromyelitis optica spectrum disorders. RESULTS: The mean age at optic neuritis onset was 73.91 ± 4.71 (range: 70-82) years with a female predominance (81.8%; ratio: 4.5:1). Antinuclear antibody seropositivity and seronegativity were identified in 12 (55.5%) and 10 (45.5%) patients, respectively. Severe visual loss persisted in 19 (19/42, 45.3%) eyes at the last follow-up. Although patients with antinuclear antibody seropositivity had a significantly higher frequency of attacks (P = 0.015), but they had a longer median time to reach severe visual loss (37 vs. 26 months; log-rank test, P = 0.023). Multivariate logistic regression analysis revealed antinuclear antibody seropositivity (hazard ratio = 4.849, 95% confidence interval: 1.309-17.965, P = 0.018) as a good predictor of visual acuity improvement. CONCLUSION: Patients with very late-onset neuromyelitis optica spectrum disorder-related optic neuritis may develop severe optic neuritis, and those with antinuclear antibody seronegativity have a similar clinical presentation but worse outcome than those with seropositivity.

Prevalence and sociodemographic correlates of antinuclear antibody testing by indirect immunofluorescence or solid-phase assays in a Spanish population: the Camargo Cohort.

Autoantibodies are the hallmark of autoimmunity, and specifically, antinuclear antibodies (ANA) are one of the most relevant antibodies present in systemic autoimmune diseases (AID). In the present study, we evaluate the relationship between ANA and sociodemographic and biobehavioral factors in a population with a low pre-test probability for systemic AID. ANA were determined in serum samples at baseline visit from 2997 participants from the Camargo Cohort using indirect immunofluorescence assay, and two solid phase assays (SPA), addressable laser bead immunoassay, and fluorescence enzyme immunoassay. Sociodemographic and biobehavioral features of the subjects were obtained at baseline visit using a structured questionnaire. The prevalence of ANA positive results was significantly higher when indirect immunofluorescence assay was used as screening method in comparison with SPAs, being higher in females, older subjects, and those with higher C-reactive protein levels. Considering biobehavioral features, the prevalence was higher in those individuals with a sedentary lifestyle, and in ex- and non-alcohol users. Moreover, considering the relevance of the antibody load using ANA Screen, the prevalence of the antibody load also increased with age, especially in females. In conclusion, the prevalence of ANA varies depending on sociodemographic and biobehavioral features of the subjects, which could be relevant specifically in a population with a low pre-test probability for systemic AIDs.

[Neurosarcoidosis: Onset with involvement of multiple neurological sites]. / Neurosarcoidosis: inicio con compromiso de múltiples sitios neurológicos.

We present the case of a healthy young woman who consulted for left peripheral facial palsy associated with fever, dry cough, dyspnea, and asthenia of two weeks' evolution. Physical examination revealed hypoesthesia in left T6 to T12 dermatomes and bilateral galactorrhea. In the laboratory, she presented negative viral serology, elevated erythrocyte sedimentation rate, antinuclear antibody titers, prolactin and thyroid-stimulating hormone, with positive antiperoxidase antibodies. Computed tomography showed multiple bilateral cervical, mediastinal, and hilar adenopathies, without involvement of lung parenchyma. Cerebrospinal fluid culture was negative for common germs, mycobacteria, and Xpert MTB/RIF, and cytology did not show atypia. Contrast-enhanced magnetic resonance was performed on the brain without pathological findings and on the spine with alteration of the centromedullary signal from T6 to T9 of almost the entire thickness of the cord, with posterior enhancement with gadolinium. During hospitalization, she recovered sensitivity in the left trunk and did not repeat febrile or cough episodes. She was referred to another center for mediastinoscopy with lymph node biopsy revealing the presence of numerous non-caseating granulomas compatible with sarcoidosis. It was classified as probable neurosarcoidosis and started treatment with corticosteroids with improvement of the remaining neurological symptoms. A magnetic resonance was performed three months later where the signal alteration was limited from T7 to T8. Our objective is to highlight the florid neurological presentation that made it necessary to rule out other more frequent entities and the favorable evolution even before starting a first-line scheme of treatment.

Presentamos el caso de una mujer joven sana, que consultó por parálisis facial periférica izquierda asociada a fiebre, tos seca, disnea y astenia de dos semanas de evolución. Al examen físico se evidenció hipoestesia en dermatomas D6 a D12 izquierdos y galactorrea bilateral. En el laboratorio presentaba serologías virales negativas, eritrosedimentación, títulos de anticuerpos antinucleares, prolactina y hormona tiroestimulante elevados, con anticuerpos antiperoxidasa positivos. La tomografía computarizada mostró múltiples adenopatías cervicales, mediastinales e hiliares bilaterales, sin compromiso del parénquima pulmonar. El cultivo de líquido cefalorraquídeo fue negativo para gérmenes comunes, micobacterias (Xpert MTB/RIF), y la citología no mostró atipia. Se realizó una resonancia magnética con contraste endovenoso de cerebro sin hallazgos patológicos y de columna con alteración de la señal centromedular de D6 a D9 de casi la totalidad del espesor del cordón, con refuerzo con contraste endovenoso. Durante la internación recuperó la sensibilidad en tronco izquierdo y no repitió episodios febriles o tusígenos. Se realizó mediastinoscopía con biopsia ganglionar con anatomía patológica con presencia de numerosos granulomas no caseificantes compatibles con sarcoidosis. Se clasificó como neurosarcoidosis probable e inició tratamiento con corticoides con mejoría de los síntomas neurológicos restantes, realizándose una resonancia magnética a los tres meses, donde la alteración de la señal se limitaba desde D7 a D8. Nuestro objetivo es destacar la presentación neurológica en múltiples sitios que obligó a descartar otras entidades más frecuentes, así como la evolución favorable incluso previo al inicio de un esquema de tratamiento de primera línea.

CONSIDERATIONS FOR INTRADERMAL APPLICATION OF IMMUNIZATION WITH NATIVE AUTOLEUKOCYTES IN MEDICINE.

OBJECTIVE: The aim: Analyzing literature sources, to assess possibilities of using the method of intradermal immunization with native autoleukocytes to treat different diseases, to investigate the areas of usage, efficacy and expediency of the technique in clinical practice. PATIENTS AND METHODS: Materials and methods: Analysis of literature sources associated with intradermal immunization with native autoleukocytes. CONCLUSION: Conclusions: The possibilities of using the method of intradermal immunization with native autoleukocytes in the treatment of various diseases are consid¬ered in the literature review. Intradermal immunization with autoleukocytes is one of the methods of personalized medicine. The application of the method results in normalization of the immune system condition as well as suppression of autoimmune and inflammatory processes. It also reduces the synthesis of pro-inflammatory cytokines and strengthens cellular antiviral immunity in a number of viral infections. It is proved, in particular, that the method reduces the synthesis of cryoglobulins, the formation of antithyroid antibodies, normalizes the level of tumor necrosis factor alpha, as well as reduces extrahepatic manifestations of chronic hepatitis and increases the effectiveness of antiviral therapy in patients with viral hepatitis B. Considering that immunization with native autoleukocytes has no contraindications, it can be used in many diseases.

The Immunodiagnostic Utility of Antinuclear Antibody Patterns: A Prediction for Renal Involvement in Systemic Lupus Erythematosus Patients in the Western Region of Saudi Arabia.

Objectives Previous studies have noted associations between the immunofluorescence patterns of antinuclear autoantibodies (ANA) and the autoimmune responses seen in systemic lupus erythematosus (SLE). In this study, the authors tested the hypothesis of whether ANA patterns predict renal involvement in SLE patients. Method A retrospective study was carried out on consecutive SLE patients who had ANA staining pattern data and who were screened for renal involvement defined as all-stage proteinuria or chronic kidney disease (CKD) at a referral tertiary center in western Saudi Arabia from December 2021 to February 2022. Demographic data and levels of lupus immune markers including ANA titers, anti-double-stranded deoxyribonucleic acid antibodies (anti-dsDNA), complements C3 and C4, anticardiolipin (aCL) immunoglobulin (Ig) G and IgM, anti-ß2 glycoprotein (ß2-IgM and ß2-IgG), and lupus anticoagulant (LA) antibodies were collected. Result Among 243 patients included, 25.1% had renal involvement (95% confidence interval {CI}=19.8-31.0). A mixed ANA pattern was associated with a higher prevalence of renal involvement (46.2%), followed by homogenous (26.5%) and speckled (25.6%) patterns, compared with 4.5% for the other patterns (p=0.044). No further association of renal involvement was observed with other biological markers. Adjusted logistic regression showed age (odds ratio {OR}=0.95; 95% CI=0.92-0.97) and mixed ANA pattern (OR=26.66; 95% CI=2.53-281.11) to be independently associated with renal involvement, explaining 12.6% of the variance. Conclusion A mixed homogenous/speckled ANA staining pattern is associated with an increased risk of renal involvement, independent of ANA titer or other lupus immune markers. The potential clinical applications of the ANA staining pattern in SLE should be explored in various subtypes of SLE and patient groups.