anti-Ro Research Articles

Decreased Th1 Cells and Increased Th2 Cells in Peripheral Blood Are Associated with Idiopathic Inflammatory Myopathies Patients with Interstitial Lung Disease.

Interstitial lung disease (ILD) is a highly fatal manifestation of idiopathic inflammatory myopathies (IIMs). Th cells play important roles in the initiation of ILD. Here, we investigated the clinical significance of peripheral blood Th cells in IIMs-ILD patients. Eleven healthy controls (HC) and 53 patients diagnosed with IIMs were included, including 30 with ILD (IIMs-ILD) and 23 without ILD (IIMs-non-ILD). Circulating Th1, Th2, Th17, and Treg cells were examined by flow cytometry, and their correlation with clinical and laboratory findings was analyzed by Spearman's correlation and logistic regression. The proportion of Th1 cells decreased and Th2 cells increased in IIMs-ILD compared with IIMs-non-ILD (median (quartile): 2.99 (1.59-5.39) vs. 6.91 (3.48-10.04), p < 0.001; 2.67 (1.79-4.67) vs. 1.62 (0.85-2.66), p = 0.006) and correlated with disease activity. The Th1-cell proportion decreased in anti-MDA5 antibody-positive patients, while the Th2 cell proportion increased in patients with nonspecific interstitial pneumonia compared with IIMs-non-ILD (2.66 (1.06-4.35) vs. 6.91 (3.48-10.04), p = 0.002; 3.09 (2.03-5.72) vs. 1.62 (0.85-2.66), p = 0.016). Univariate analysis showed that a lower Th1 proportion, higher Th2 proportion increased, lower CK level, positivity for ARS, or anti-Ro52 antibodies (OR = 0.7122; OR = 1.679; OR = 0.9993; OR = 9.188; and OR = 6.161, respectively) were associated with the occurrence of ILD in IIMs patients. Decreased Th1 cells and elevated Th2 cells in peripheral blood may be involved in the pathogenesis of ILD in IIMs patients and have different effects on different serological and imaging subtypes.

Severe extra-glandular involvement and pleural effusions complicating primary Sjogren’s syndrome: a case report

BackgroundSjogren’s syndrome, an autoimmune disease of the exocrine glands, results in keratoconjunctivitis sicca, xerostomia, and dental caries. It is often overlooked, considered by clinicians to be a benign disease. However, it can cause life-threatening extra-glandular complications that affect multiple organ systems.Case presentationHere we present a 78-year-old Caucasian woman with a history of primary Sjogren’s syndrome (pSS) whose symptoms of keratoconjunctivitis sicca were managed managed conservatively. She was evaluated for sub-acute shortness of breath. Imaging showed severe bronchiectasis with features of lymphocytic interstitial pneumonia. She also had exudative bilateral pleural effusions and skin ulcers, likely vasculitic in origin. The workup was significant for anti-Ro antibody, pancytopenia, hypocomplementia, cryoglobulinemia and monoclonal gammopathy, all of which reflect disease severity. Although there was no evidence of malignancy, she developed B-cell non-Hodgkin lymphoma during follow-up.ConclusionsPrimary Sjogren’s syndrome can result in severe multi-organ disease. Pleural effusions are a rare complication of pSS, with only ten cases reported in the literature over the last 30 years, and tend to respond well to steroids. Prognostic biomarkers for disease severity include hypocomplementia, cryoglobulinemia, monoclonal gammopathy, and hypergammaglobulinemia. In this report we review the literature and the management of the disease.

Roles of biomarkers in anti-MDA5-positive dermatomyositis, associated interstitial lung disease, and rapidly progressive interstitial lung disease.

Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (MDA5+ DM) is significantly associated with interstitial lung disease (ILD), especially rapidly progressive ILD (RPILD) due to poor prognosis, resulting in high mortality rates. However, the pathogenic mechanism of MDA5+ DM-RPILD is unclear. Although some MDA5+ DM patients have a chronic course of ILD, many do not develop RPILD. Therefore, the related biomarkers for the early diagnosis, disease activity monitoring, and prediction of the outcome of RPILD in MDA5+ DM patients should be identified. Blood-based biomarkers are minimally invasive and can be easily detected. Recent relative studies related to blood biomarkers in PubMed were reviewed. An increasing number of studies have demonstrated that dysregulated expression of blood biomarkers related to ILD such as ferritin, Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D), and cytokines, and some tumor markers in MDA5+ DM may provide information in disease presence, activity, treatment response, and prognosis. These studies have highlighted the great potentials of blood biomarker values for MDA5+ DM-ILD and MDA5+ DM-RPILD. This review provides an overview of recent studies related to blood biomarkers, besides highlighted protein biomarkers, including antibody (anti-MDA5 IgG subclasses and anti-Ro52 antibody), genetic (exosomal microRNAs and neutrophil extracellular traps related to cell-free DNA), and immune cellular biomarkers in MDA5+ DM, MDA5+ DM-ILD, and MDA5+ DM-RPILD patients, hopefully elucidating the pathogenesis of MDA5+ DM-ILD and providing information on the early diagnosis, disease activity monitoring, and prediction of the outcome of the ILD, especially RPILD. Therefore, this review may provide insight to guide treatment decisions for MDA5+ DM-RPILD patients and improve outcomes.

Alternative exon usage in TRIM21 determines the antigenicity of Ro52/TRIM21 in systemic lupus erythematosus.

The origin and mechanisms of autoantigen generation in systemic lupus erythematosus (SLE) are poorly understood. Here, we identified SLE neutrophils activated in vivo by IFN as a prominent source of Ro52, also known as tripartite motif-containing protein 21 (TRIM21), a critical autoantigen historically thought to be primarily generated by keratinocytes in SLE. Different from mononuclear cells and keratinocytes, SLE neutrophils are enriched in several unique Ro52 species containing a core sequence encoded by exon 4 (Ro52Ex4) in TRIM21. Ro52Ex4 is the main target of anti-Ro52 antibodies and is found in 2 Ro52 variants (Ro52α and a potentially novel isoform termed Ro52γ) upregulated in SLE neutrophils. Further analysis of Ro52γ revealed a subset of autoantibodies against a unique C-terminal domain (Ro52γCT) generated from a frameshift due to the lack of exon 6 in Ro52γ. Antibodies to Ro52Ex4 and Ro52γCT distinguish SLE patient subsets characterized by distinct clinical, laboratory, treatment, and transcriptional profiles that are not discerned by the "classical" anti-Ro52 antibodies. These studies uncover IFN-activated neutrophils as a key source of unique immunogenic forms of Ro52 in SLE. Moreover, the finding of Ro52Ex4 and Ro52γCT as core targets of anti-Ro52 antibodies focus interest on Ro52γ as the potential isoform toward which immunological tolerance is initially lost in SLE.

Should Aquaporin-4 Antibody Test Be Performed in all Patients With Isolated Optic Neuritis?

Optic neuritis (ON) may be the initial manifestation of neuromyelitis optica spectrum disorder (NMOSD). Aquaporin-4 antibody (AQP4 Ab) is used to diagnose NMOSD. This has implications on prognosis and is important for optimal management. We aim to evaluate if clinical features can distinguish AQP4 Ab seropositive and seronegative ON patients. We reviewed patients with first episode of isolated ON from Tan Tock Seng Hospital and Singapore National Eye Centre who tested for AQP4 Ab from 2008 to 2017. Demographic and clinical data were compared between seropositive and seronegative patients. Among 106 patients (120 eyes) with first episode of isolated ON, 23 (26 eyes; 22%) were AQP4 Ab positive and 83 (94 eyes; 78%) were AQP4 Ab negative. At presentation, AQP4 Ab positive patients had older mean onset age (47.9 ± 13.6 vs 36.8 ± 12.6 years, P < 0.001), worse nadir VA (OR 1.714; 95% CI, 1.36 to 2.16; P < 0.001), less optic disc swelling (OR 5.04; 95% CI, 1.682 to 15.073; p = 0.004), and higher proportions of concomitant anti-Ro antibody (17% vs 4%, p = 0.038) and anti-La antibody (17% vs 1%, p = 0.008). More AQP4 Ab positive patients received steroid-sparing immunosuppressants (74% vs 19%, p < 0.001) and plasma exchange (13% vs 0%, p = 0.009). AQP4 Ab positive patients had worse mean logMAR VA (visual acuity) at 12 months (0.70 ± 0.3 vs 0.29 ± 0.5, p = 0.051) and 36 months (0.37±0.4 vs 0.14 ± 0.2, p = 0.048) follow-up. Other than older onset age and retrobulbar optic neuritis, clinical features are non-discriminatory for NMOSD. We propose a low threshold for AQP4 Ab serology testing in inflammatory ON patients, particularly in high NMOSD prevalence populations, to minimize diagnostic and treatment delays.

Positive Autoantibody Is Associated with Malignancies in Patients with Idiopathic Interstitial Pneumonias.

Various autoantibodies are associated with clinical outcomes in patients with idiopathic interstitial pneumonias (IIPs). We retrospectively analyzed the association between autoantibodies and malignancies in IIP patients. Comprehensive analyses of autoantibodies were performed using immunoprecipitation and enzyme-linked immunosorbent assays in 193 consecutive IIP patients. Cancer-related factors were analyzed using logistic regression analysis. In total, 22 of 193 patients (11.4%) with IIP had malignant disease. In univariate analysis, positivity for any autoantibody (odds ratio (OR), 3.1; 95% confidence interval (CI), 1.2–7.7; p = 0.017) and antinuclear antibody titer ≥1:320 (OR, 3.4; CI, 1.2–9.8; p = 0.024) were significantly associated with malignancies. Positive anti-aminoacyl tRNA synthetase (ARS) (OR, 3.7; CI, 0.88–15.5; p = 0.074) and anti-Ro52 antibody (OR, 3.2; CI, 0.93–11.2; p = 0.065) tended to be associated with malignancies. In multivariate analysis, independent risk factors were male sex (OR, 3.7; CI, 1.0–13.5; p = 0.029) and positivity for any autoantibody (OR, 3.9; CI, 1.5–10.1; p = 0.004) in model 1, and male sex (OR, 3.9; CI, 1.0–15.3; p = 0.049), antinuclear antibody titer ≥1:320 (OR, 4.2; CI, 1.4–13.3; p = 0.013), and positivity for anti-ARS antibody (OR, 6.5; CI, 1.2–34.1; p = 0.026) in model 2. Positivity for any autoantibody, antinuclear and anti-ARS antibodies, and male sex were independent risk factors for malignancies in IIP patients. Testing autoantibodies in IIP patients might help the early diagnosis of malignancies.

Retrospective study on clinical manifestation, thigh MRI and electrophysiology characteristics of immune-mediated necrotizing myopathy

Objective: To summarize the clinical, thigh magnetic resonance (tMRI) and electromyographic (EMG) characteristics in patients with immune-mediated necrotizing myopathy (IMNM). Methods: A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital. According to the type of antibody, the patients were divided into anti-SRP antibody positive (SRP+) group, anti-HMGCR antibody positive (HMGCR+) group and seronegative (SN) group. The gender, age, course of disease, myositis antibodies, extramuscular manifestations, EMG were collected and analyzed among three groups. The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores. Analysis of variance, Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups. When there was a statistical difference among the three groups, the comparison between the two groups was corrected by the Bonferroni method. Result: (1) Of the 32 patients, 20 were females (62.5%).The median age of onset was 47±14 years, 25 (78.1%) patients had an acute or subacute course.There were 17 (53.1%) with SRP+, 8 (25.0%) with HMGCR+, and 7 (21.9%) with MSAs (myositis specific antibodies) negative. Anti-Ro52 antibody was the most common combined antibody (12/32, 37.5%), among which 10 were in SRP+group.(2) The CK of all patients were elevated, median was 5 948 (4 229, 7 664) U/L. There was no statistical difference of MMT scores among three groups. The proximal limb score was lower than distal limb (P<0.01). The axial muscle score was lower than the distal limb score (P<0.05).(3) Extramuscular manifestations of HMGCR+ group were lower than those of the other two groups (12.5% vs. 71.4% and 76.5%, P<0.017). Rash (60.0% vs.14.3%, P<0.05) and interstitial pulmonary diseases (70.0% vs. 14.3%, P<0.05) were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP. Connective tissue disease was more common in SN group (57.1% vs. 11.8% and 0, P<0.017).(4) tMRI showed fascial edema of SN group was more obvious than that of the other two groups (P<0.017). There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups, but SRP+ group had more cases of early fat infiltration.(5) Myotonic potentials (25.0% vs. 0 and 0, P<0.017) and compound repetitive discharges (CRDs) (50.0% vs. 5.9% and 0, P<0.017) were common in HMGCR+ group. Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton, cell junction and extracellular matrix. Conclusion: IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles. Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations, which might be a special subtype of SRP+ group. This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury. EMG of HMGCR+group were more prone to myotonia potential and CRDs.

AN UNCOMMON PRESENTATION OF ANTISYNTHETASE SYNDROME-RELATED INTERSTITIAL LUNG DISEASE IN A YOUNG INDIAN MALE

AN UNCOMMON PRESENTATION OF ANTISYNTHETASE SYNDROME-RELATED INTERSTITIAL LUNG DISEASE IN A YOUNG INDIAN MALE

DERMATOMYOSITIS WITH RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE COMPLICATED BY SPONTANEOUS PNEUMOMEDIASTINUM IN A PATIENT AFTER ASYMPTOMATIC COVID-19 INFECTION

DERMATOMYOSITIS WITH RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE COMPLICATED BY SPONTANEOUS PNEUMOMEDIASTINUM IN A PATIENT AFTER ASYMPTOMATIC COVID-19 INFECTION

P24 A case of limited cutaneous systemic sclerosis evolving into an overlap syndrome with systemic lupus erythematosus and pyoderma gangrenosum

P24 A case of limited cutaneous systemic sclerosis evolving into an overlap syndrome with systemic lupus erythematosus and pyoderma gangrenosum

Prediction model for the pretreatment evaluation of mortality risk in anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease.

BackgroundAnti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease (anti-MDA5 DM-ILD) is a disease with high mortality. We sought to develop an effective and convenient prediction tool to estimate mortality risk in patients with anti-MDA5 DM-ILD and inform clinical decision-making early.MethodsThis prognostic study included Asian patients with anti-MDA5 DM-ILD hospitalized at the Nanjing Drum Hospital from December 2016 to December 2020. Candidate laboratory indicators were retrospectively collected. Patients hospitalized from 2016 to 2018 were used as the discovery cohort and applied to identify the optimal predictive features using a least absolute shrinkage and selection operator (LASSO) logistic regression model. A risk score was determined based on these features and used to construct the mortality risk prediction model in combination with clinical characteristics. Results were verified in a temporal validation comprising patients treated between 2019 and 2020. The primary outcome was mortality risk within one year. The secondary outcome was overall survival. The prediction model’s performance was assessed in terms of discrimination, calibration, and clinical usefulness.ResultsThis study included 127 patients, (72 men [56.7%]; median age, 54 years [interquartile range, 48-63 years], split into discovery (n = 87, 70%) and temporal validation (n=37, 30%) cohorts. Five optimal features were selected by LASSO logistic regression in the discovery cohort (n = 87) and used to construct a risk score, including lymphocyte counts, CD3+CD4+ T-cell counts, cytokeratin 19 fragment (CYFRA21-1), oxygenation index, and anti-Ro52 antibody. The retained predictive variables in the final prediction model were age, Heliotrope, fever, and risk score, and the most predictive factor was the risk score. The prediction model showed good discrimination (AUC: 0.915, 95% CI: 0.846–0.957), good calibration (Hosmer–Lemeshow test, P = 0.506; Brier score, 0.12), and fair clinical usefulness in the discovery cohort. The results were verified among patients in the temporal validation cohort (n = 38). We successfully divided patients into three risk groups with very different mortality rates according to the predictive score in both the discovery and validation cohorts (Cochran-Armitage test for trend, P < 0.001).ConclusionsWe developed and validated a mortality risk prediction tool with good discrimination and calibration for Asian patients with anti-MDA5 DM-ILD. This tool can offer individualized mortality risk estimation and inform clinical decision-making.

Proceedings of the 28th European Paediatric Rheumatology Congress (PReS 2022)

Proceedings of the 28th European Paediatric Rheumatology Congress (PReS 2022)

Immunological characteristics of IgG4-related Kuttner tumors.

Immunoglobulin G4-related disease (IgG4-RD) has recently been well recognized and Kuttner tumor is known to be a chronic sclerosing sialadenitis, representing the focal manifestation of IgG4-RD, in the submandibular gland (SMG). This study is to evaluate the immunologic features of IgG4-related Kuttner tumor in the SMG. We retrospectively chose 13 patients who were confirmed as having Kuttner tumor by surgical biopsy between May 2012 and January 2019. The fine-needle aspiration cytology, serum antibody levels (anti-Ro antibodies, anti-La antibodies), IgG serum levels (total IgG and IgG4), and immunohistochemical findings for IgG and IgG4-positive plasma cells were reviewed. The cytologic results found that 7 of the 9 cases were reported as chronic sialoadenitis, and the other 3 as benign lymphoproliferative lesion. The serum levels of autoantibodies, Sjögren-syndrome-related antigen A/Ro-Ab and Sjögren-syndrome-related antigen A/Ro-La, showed all normal values of serum level. The serum level of IgG was increased in only 4 among the cases. However, the IgG4 levels were significantly increased in 11 among the cases. In all the patients who received resection of SMG, immunohistochemical findings showed all positive for IgG4-RD, with elevated numbers of IgG and IgG4-positive plasma cells. The evaluation of IgG4 serum level should be very informative for the diagnosis of this tumor before surgery. Fine-needle aspiration cytology with ultrasound guidance are not conclusive in this study. The immunological study including IgG4 serum level should be required for proper diagnosis and treatment, with clinical features of the Kuttner tumor. The level of evidence was IV.

A Systematic Review and Metaanalysis of Predictors of Mortality in Idiopathic Inflammatory Myopathy-Associated Interstitial Lung Disease.

Idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD) can range from rapidly progressive disease with high mortality to indolent disease with minimal morbidity. This systematic review and metaanalysis describe immunological, clinical, and radiographical predictors of mortality in IIM-ILD. MEDLINE and Embase database searches were completed on October 18, 2021, to identify articles providing survival data according to baseline characteristics in patients with concurrent IIM and ILD. Prognostic factors common to more than 5 papers were included in the metaanalysis using a random-effects model to report odds ratios (ORs) for binary variables and Hedges g for continuous variables. Risk of bias was assessed using the Newcastle-Ottawa Scale score and the Egger test for publication bias. From 4433 articles, 62 papers were suitable for inclusion; among these studies, 38 different variables were considered. The OR for risk of death regarding the presence of anti-melanoma differentiation-associated protein 5 (MDA5) antibodies was 6.20 (95% CI 3.58-10.71), and anti-tRNA synthetase antibodies were found to be protective (OR 0.24, 95% CI 0.14-0.41). Neither antinuclear antibodies, anti-52-kDa Ro antigen antibodies, nor SSA significantly altered mortality, nor was MDA5 titer predictive. Examples of prognostic factors that are significantly associated with mortality in this study include the following: age; male sex; acute/subacute onset; clinically amyopathic dermatomyositis; dyspnea; ulceration; fever; raised C-reactive protein, ferritin, lactate dehydrogenase, alveolar to arterial O2 (A-aO2) gradient, ground-glass opacity on high-resolution computed tomography (HRCT), and overall HRCT score; and reduced albumin, lymphocytes, ratio of partial pressure of oxygen in the arterial blood to fraction of inspired oxygen (PF ratio), percentage predicted transfer factor for carbon monoxide, and percentage predicted forced vital capacity. Baseline surfactant protein-D and Krebs von den Lungen-6 levels were not predictors of mortality. Many mortality risk factors were identified, though heterogeneity was high, with a low quality of evidence and a risk of publication bias. Studies regarding anti-MDA5 antibody-positive disease and and those from East Asia predominate, which could mask risk factors relevant to other IIM subgroups or populations.

Machine Learning for the Identification of a Common Signature for Anti-SSA/Ro 60 Antibody Expression Across Autoimmune Diseases.

Anti-Ro autoantibodies are among the most frequently detected extractable nuclear antigen autoantibodies, mainly associated with primary Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), and undifferentiated connective tissue disease (UCTD). This study was undertaken to determine if there is a common signature for all patients expressing anti-Ro 60 autoantibodies regardless of their disease phenotype. Using high-throughput multiomics data collected from the cross-sectional cohort in the PRECISE Systemic Autoimmune Diseases (PRECISESADS) study Innovative Medicines Initiative (IMI) project (genetic, epigenomic, and transcriptomic data, combined with flow cytometry data, multiplexed cytokines, classic serology, and clinical data), we used machine learning to assess the integrated molecular profiling of 520 anti-Ro 60+ patients compared to 511 anti-Ro 60- patients with primary SS, patients with SLE, and patients with UCTD, and 279 healthy controls. The selected clinical features for RNA-Seq, DNA methylation, and genome-wide association study data allowed for a clear distinction between anti-Ro 60+ and anti-Ro 60- patients. The different features selected using machine learning from the anti-Ro 60+ patients constituted specific signatures when compared to anti-Ro 60- patients and healthy controls. Remarkably, the transcript Z score of 3 genes (ATP10A, MX1, and PARP14), presenting with overexpression associated with hypomethylation and genetic variation and independently identified using the Boruta algorithm, was clearly higher in anti-Ro 60+ patients compared to anti-Ro 60- patients regardless of disease type. Our findings demonstrated that these signatures, enriched in interferon-stimulated genes, were also found in anti-Ro 60+ patients with rheumatoid arthritis and those with systemic sclerosis and remained stable over time and were not affected by treatment. Anti-Ro 60+ patients present with a specific inflammatory signature regardless of their disease type, suggesting that a dual therapeutic approach targeting both Ro-associated RNAs and anti-Ro 60 autoantibodies should be considered.

Characterisation of Disease Patterns of Dermatomyositis with Different Initial Manifestations.

PurposeTo determine the characteristics and prognoses of dermatomyositis (DM) by comparing the difference in initial symptoms.Patients and MethodsA retrospective analysis was performed on the patients diagnosed with DM from 1 January 2019 to 1 January 2021. Based on the firstly presented symptoms, patients were divided into five groups, namely rash group, muscle weakness group, arthritis group, respiratory symptom group and atypical symptom group. Clinical and laboratory data were recorded. All patients were followed up until 31 May 2021.ResultsIn total 136 DM patients, rash (40%) was the most common initial symptom, followed by respiratory symptoms (22%), arthritis (20%), muscle weakness (10%) and atypical symptoms (8%). Rash group and atypical group had a higher positive rate of anti-TIF1γ antibodies than arthritis group and respiratory symptom group (P < 0.05). Respiratory symptom and arthritis groups had a higher positive rate of anti-Ro52 antibodies than rash and muscle weakness groups (P < 0.05). Respiratory group had a higher incidence of ILD than rash and atypical groups. The FVC and DLCO in respiratory group were significantly lower than rash group, arthritis group and atypical group (P < 0.05). The survival rate of rash group was significantly higher than muscle weakness group and arthritis group (P < 0.05).ConclusionDM patients with different initial manifestations had different myositis antibodies and prognoses.

Cardiac manifestations in a Chinese cohort of fetuses from mothers with anti-Ro and anti-La antibodies.

ObjectivesTo analyze the clinical characteristics, echocardiographic features, and prognosis of fetuses based on three groups of cardiac manifestations associated with maternal anti-Ro and anti-La antibodies in China. This study included three groups: the isolated-arrhythmia, isolated-endocardial fibroelastosis (EFE), and mixed groups.MethodsWe prospectively evaluated 36 fetuses with cardiac manifestations due to maternal anti-Ro and anti-La antibodies from our center between 2016 and 2020 in China. Clinical and echocardiographic data were collected.ResultsThere were 13 patients (36%) in the isolated-arrhythmia group, eight (22%) in the isolated-EFE group, and 15 (42%) in the mixed group. All patients in the isolated-EFE group presented with mild EFE. Severe EFE was identified in four patients (27%) in the mixed group. Atrioventricular block (AVB) was more common in the isolated-arrhythmia group (13, 100%) than in the mixed group (6, 40%; p = 0.001). Moderate-severe mitral regurgitation (p = 0.006), dilated cardiomyopathy (DCM, p = 0.017), and low cardiovascular profile scores (p = 0.013) were more common in the mixed group than in the other two groups. Twenty-one mothers decided to terminate the pregnancy and 15 fetuses were born with regular perinatal treatment. They all survived at 1 year of age. One patient in the isolated-arrhythmia group and two in the mixed group required a pacemaker due to third-degree AVB or atrioventricular junctional rhythm. Five patients in the isolated-EFE group and five in the mixed group had no DCM or heart failure and the location of mild EFE was significantly reduced.ConclusionFetal cardiac manifestations due to maternal anti-Ro and anti-La antibodies can be divided into three groups, i.e., the isolated-arrhythmia, isolated-EFE, and mixed groups. AVB usually occurs in the isolated-arrhythmia group. Severe EFE, moderate-severe mitral regurgitation, and DCM mainly appear in the mixed group. Location of mild EFE significantly reduces after birth and the outcome of fetuses with mild EFE depends on the presence of arrhythmia and its subtypes.

Patterns of Antinuclear Antibodies in a New Variant of Endemic Pemphigus in El Bagre, Colombia, Colocalizing with Antigens against MIZAP, ARVCF, p0071, and Desmoplakins I and II.

A new variant of endemic pemphigus foliaceus (EPF) has been documented, El Bagre-EPF. We aimed to study antinuclear antibodies (ANAs) in these patients. We performed a case-control study, testing 57 patients affected by this disease and 57 controls from the endemic area matched by work activity and demographics. The participants were evaluated clinically as well as by detection of ANAs utilizing HEp-2 cells. We utilized Triton-induced partial permeabilization of the cell membranes, allowing for the visualization of intracellular and intranuclear antigens. We also immunoadsorbed the ANAs using synthetic peptides to elucidate the nature of the ANA. We detected the presence of a new pattern of ANAs. The new pattern of ANAs was seen in 24% of the El Bagre-EPF patients, compared to our controls (P < 0.001). The new ANA pattern consisted of a thin nuclear and nucleolar rim, finely speckled nucleolar, nuclear membrane pores stains, and a positive intranuclear stain directed against small nuclear components, as well as cytoplasmic deposits of autoantibodies were also observed. The new ANAs pattern perfectly colocalized with commercial antibodies to miocardium-enriched zonula occlusans-1 associated protein (MIZAP), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), p0071 and desmoplakins I-II (all from Progen Biotechnik). Additionally in 14% of patients with El Bagre-EPF forme fruste and hyperpigmented clinical presentations, a classic homogeneous ANA pattern was observed with autoantibodies specific for Ro, La, Sm, and double-stranded DNA antigens. Immunoadsorption with peptide-based sequences from MIZAP, ARVCF, p0071 and desmoplakins I-II removed the new ANA pattern. We describe a new pattern of ANAs in El Bagre-EPF, colocalizing with autoantibodies directed against MIZAP, ARVCF, p0071, and desmoplakins I-II.

Predictive Factors for Renal Response in Lupus Nephritis: A Single-center Prospective Cohort Study.

To identify the predictive factors for renal response in patients with lupus nephritis (LN). Patients and data were extracted from a prospective systemic lupus erythematosus cohort in Korea, in which clinical data were collected at 0, 3, 6, and 12 months after induction therapy. Treatment response of LN were evaluated as a complete response (CR), partial response (PR), or non-response (NR) at 3, 6, and 12 months, respectively. Predictive factors for CR at 6 months were evaluated using multivariable Poisson regression analysis. A total of 75 patients with LN who underwent biopsy was enrolled. The mean age at diagnosis of LN was 28.9±9.7 years, and 68 (90.7%) were female. The frequencies of classes III, IV, III+V, IV+V, and V were 20.0%, 44.0%, 16.0%, 12.0%, and 8.0%, respectively. Compared to relapsed LN, new-onset LN showed a lower percentage of glomerulosclerosis (45.5% vs. 76.2%, p=0.013). The overall proportions of CR, PR, and NR at 6 and 12 months were 52.0%, 26.7%, 21.3% and 50.7%, 24.0%, 25.3%, respectively. In multivariate analysis, age at enrollment (odds ratio [OR]=1.02, p=0.022), relapsed LN (OR=0.71, p=0.037), anti-Ro antibody (OR=0.67, p=0.014), and class III LN (OR=1.48, p=0.001) were associated with CR at 6 months. In our prospective cohort, class III LN was a good predictive factor for CR at 6 months in patients with LN, whereas younger age, relapsed LN, and anti-Ro antibody were poor predictive factors.

KIKUCHI DISEASE-LIKE INFLAMMATORY PATTERN IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENT: A CASE REPORT

Kikuchi-Fujimoto disease (KFD) is a benign and rare disorder that can be a manifestation of the Kikuchi disease-like inflammatory pattern (KLIP) and coexists with systemic lupus erythematosus (SLE). The corresponding treatment of these diseases is difficult. A 66-year-old Thai man with underlying SLE presented with generalized yellowish erythematous papules and plaques throughout his body. No evidence of fever, lymphadenopathy, or hepatosplenomegaly was noted. Antinuclear antibodies (ANA) were positive but anti-dsDNA, anti-Smith, anti-snRNP, and anti-Ro antibodies were negative. The histopathology was consistent with KFD, and the patient was diagnosed with a Kikuchi disease-like inflammatory pattern. Hydroxychloroquine elicited a rapid and favorable response in the patient who remained relapse-free while on low-dose hydroxychloroquine. Here, we report the case of a 66-year-old Thai man with erythematous plaques on his chest and neck.