Presence Of anti-Ro Antibodies Research Articles

Machine learning identifies cytokine signatures of disease severity and autoantibody profiles in systemic lupus erythematosus – a pilot study

Disrupted cytokine networks and autoantibodies play an important role in the pathogenesis of systemic lupus erythematosus. However, conflicting reports and non-reproducibility have hindered progress regarding the translational potential of cytokines in SLE. This study attempts to address the existing knowledge gap using multiplex cytokine assay and machine learning. 67 SLE patients fulfilling SLICC criteria were recruited after informed consent, and circulating cytokines were measured by multiplex cytokine assay kit. We observed a positive association between actual disease activity scores (SLEDAI) and predicted scores from a partial least squares regression (PLSR) analysis of multivariate cytokine response data, with MIP-1α having a strong contribution towards disease activity. Our analysis also highlights increased IL-12 as a potential biomarker in nephritis and elevated MIP-1α as a signature of NPSLE. Using a k-Modes clustering algorithm to stratify patients based on patterns of co-occurrence of circulating autoantibodies, we identified 4 distinct clusters of patients. All 4 clusters had patients with nephritis, but patients in cluster 3 with nephritis were characterised by low levels of housekeeping and homeostatic cytokines and the presence of anti-Ro antibodies, which is a novel observation. Thus, we demonstrate that cytokines can be a surrogate to predict disease activity and organ involvement in SLE. Moreover, we show the utility of unsupervised machine learning algorithms using specific autoantibody signatures to predict renal involvement in SLE.

Should Physicians Be Aware of Rhythm Disturbances in Adults with Systemic Autoimmune Diseases and Anti-Ro52 Antibodies? A Cross-Sectional Study.

Objectives: The association between anti-Ro/SSA antibodies and the appearance of cardiac rhythm disorders in adults is discussed. We aim to study this relationship, together with active treatments and comorbidities, and its impact on daily clinical practice in adults with systemic autoimmune diseases (SADs). Methods: This cross-sectional single-center study was conducted in a tertiary hospital between January 2021 and March 2022. A sample of adult patients followed up in the SAD Unit with a diagnosis of a SAD and previously tested for anti-Ro/SSA and anti-La/SSB were recruited. All of them underwent a 12-lead electrocardiogram. Results: 167 patients were included. 90 (53.9%) were positive for anti-Ro60, 101 (60.5%) for anti-Ro52, and 45 (26.9%) for anti-La/SSB; 52 (31.3%) were triple-negative. 84% were women, and the mean age was 59 years (standard deviation 12.8). The most common SAD was primary Sjögren's syndrome (34.8%), followed by systemic lupus erythematosus (24.6%) and rheumatoid arthritis (22.8%). A statistically significant relationship was found between anti-Ro52 positivity and cardiac rhythm disorders (relative risk = 2.007 [1.197-3.366]), specifically QTc prolongation (relative risk = 4.248 [1.553-11.615]). Multivariate regressions showed a significant association, with diabetes mellitus being the most related comorbidity. The association between anti-Ro52 antibodies and atrioventricular conduction disorders was not significant. Conclusions: The presence of anti-Ro52 antibodies in adult patients with SADs is associated with an increased risk of QTc prolongation. Electrocardiographic screening of patients with SAD, anti-Ro52 antibodies, and other risk factors, like diabetes mellitus or QT-prolonging drugs, seems advisable. Those with baseline electrocardiogram abnormalities or additional risk factors should undergo electrocardiographic monitoring.

Clinical Characteristics of Anti-Synthetase Syndrome and Variables Associated with Interstitial Lung Disease and Mortality: A Retrospective Cohort Study

Anti-synthetase syndrome (ASS) is a rare autoimmune disease. Since the knowledge of ASS remains limited, we conducted the retrospective study aiming to describe clinical characteristics and identify variables associated with interstitial lung disease (ILD) and mortality among patients with ASS. Patients diagnosed with ASS from January 2013 to October 2022 were included. Patient demographics, clinical manifestations, myositis auto-antibody profiles, HRCT findings, and laboratory tests were collected. Variables associated with mortality risk and ILD were evaluated using the Cox proportional hazards model and the logistic regression model, respectively. A total of 82 patients with ASS were included. Clinical manifestations included arthritis (57%), Raynaud’s phenomenon (32%), mechanic’s hands (29%), fever (26%), and myositis (17%). The myositis auto-antibody profiles included anti-PL-7 (29%), anti-Jo-1 (27%), anti-EJ (17%), anti-PL-12 (16%), and anti-OJ (11%). ILD was observed in 64 patients (78%). Among patients with ILD, 21 initially presented with ILD before developing other ASS clinical manifestations, 29 simultaneously presented with ILD and other symptoms, and 14 had isolated ILD throughout follow-up. Overall, 6 patients presented with rapid-progressive ILD. With a median follow-up time of 2.5 years, mortality was observed in 10 patients (12.2%). Factors associated with mortality included increased lymphocyte counts (adjusted HR, 0.74; 95% CI, 0.61–0.91; p < 0.01), isolated ILD (adjusted HR, 9.59; 95% CI, 1.52–60.61; p = 0.02) and the presence of anti-Ro52 antibodies (adjusted HR, 0.14; 95% CI, 0.02–0.93; p = 0.04). Factors associated with ILD included age (adjusted OR, 1.10; 95% CI, 1.03–1.18; p = 0.01), presence of anti-Ro52 antibodies (adjusted OR, 17.92; 95% CI, 2.13–138.68; p = 0.01), and presence of arthritis (adjusted OR, 0.09; 95% CI, 0.01–0.75; p = 0.03). Our study demonstrated a favorable overall mortality rate among ASS patients.

Tofacitinib counteracts IL-6 overexpression induced by deficient autophagy: implications in Sjögren's syndrome.

Altered homeostasis of salivary gland (SG) epithelial cells in Sjögren's syndrome (SS) could be the initiating factor that leads to inflammation, secretory dysfunction and autoimmunity. Autophagy is an important homeostatic mechanism, whose deficiency is associated with inflammation and accumulation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) components. We aimed to evaluate whether autophagy is altered in labial SG (LSG) epithelial cells from primary SS (pSS) patients and whether this contributes to inflammation through the JAK-STAT pathway. Furthermore, we investigated the anti-inflammatory effect of the JAK inhibitor tofacitinib in autophagy-deficient (ATG5 knockdown) three-dimensional (3D)-acini. We analysed LSG biopsies from 12 pSS patients with low focus score and 10 controls. ATG5-deficient 3D-acini were generated and incubated with IL-6 in the presence or absence of tofacitinib. Autophagy markers, pro-inflammatory cytokine expression, and JAK-STAT pathway activation were evaluated by PCR or western blot, along with correlation analyses between the evaluated markers and clinical parameters. LSG from pSS patients showed increased p62 and decreased ATG5 expression, correlating negatively with increased activation of JAK-STAT pathway components (pSTAT1 and pSTAT3). Increased expression of STAT1 and IL-6 correlated with EULAR Sjögren's syndrome disease activity index and the presence of anti-Ro antibodies. ATG5-deficient 3D-acini reproduced the findings observed in LSG from pSS patients, showing increased expression of pro-inflammatory markers such as IL-6, which was reversed by tofacitinib. Decreased expression of ATG5 in LSG epithelial cells from pSS patients possibly contributes to increased inflammation associated with JAK-STAT pathway activation, as evidenced in ATG5-deficient 3D-acini. Interestingly, these results suggest that tofacitinib could be used as an anti-inflammatory agent in pSS patients.

AB0624 PREDICTIVE PARAMETERS FOR DEVELOPMENT OF INTERSTITIAL LUNG DISEASE IN IDIOPATHIC INFLAMMATORY MYOSITIS

Background:Idiopathic Inflammatory Myositis (IIM) is a group of heterogeneous connective tissue diseases, primarily characterized by chronic muscle inflammation as well as myositis-specific or myositis-associated autoantibodies and a spectrum of different extra-muscular features.The most frequent organ involment in IIM is Interstitial Lung Disease (ILD), occurring in 5-80% of different IIMs cases and considered the hallmark of morbidity and mortality in patients with IIMs.Objectives:To retrospectively assess the predictive factors for development of ILD in IIM patientsMethods:We retrospectively analyzed the prevalence of ILD in a single-center cohort of 165 IIM patients. Patient data was collected from clinical charts. ILD was diagnosed by chest X-ray scan and chest CT scan. All chest CT and chest X-ray scans available and performed at our hospital were consequently re-evaluated by our expert pneumologist for uniform evaluation.Results:Myositis-related ILD (M-ILD) was found in 52 IIM patients (31.5%): 46.15% was affected by anti-synthetase syndrome (ARS), 21.15% by polymyositis (PM), 19.23% by dermatomyositis (DM) and 13.46% by overlap myositis. The pulmonary involvement was characterized by Non-specific interstitial pneumonia (NSIP) (30.6%), Unusual Interstitial Pneumonia (UIP) (38.77%), Bronchiolitis Obliterans with Organizing Pneumonia (BOOP) (20.4%), overlap NSIP/BOOP (4.1%) and Undetermined/Unspecific pattern (6.12%). Eighty four percent of M-ILD consisted of non-smokers and 69.23% presented with dyspnea at onset.ILD was diagnosed in 90.38% of patients within the first year of IIM diagnosis (early onset ILD) and was associated with dyspnea and/or cough in 70.2% and 17% respectively. On the other hand, late onset ILD presented mostly with dyspnea and/or cough in 60% of cases and was significantly associated with anti-Ku antobodies.At onset ILD was significantly associated with: ARS (p<0.0001; OR:12.98), anti-Jo-1 (p<0.0001; OR:6.1), anti-Ro (p=0.038; OR:2.2), mechanic’s hands (p<0.0001; OR:10.41), arthritis (p=0.01; OR:2.58), polyarthritis (p=0.001; OR:4.578), dyspnea (p<0.0001; OR:9.66), and high levels of CPK (p=0.0001) and GOT (p=0.0146). By contrast, the following features: DM (p=0.012; OR:0.36), facial rash (p=0.003; OR:0.31), anti-NXP-2 (p=0.019; OR<0.0001), anti-PL-12 (p=0,03; OR<0.0001) and myositis (p<0.0001; OR:0.173) present at onset were less frequently associated with M-ILD.At multivariate analysis M-ILD was predicted by anti-Ro (p=0.0448), polyarthritis (p=0.0093) and dyspnea (p=0.0001) at onset. On the other hand, patients presenting myositis (p=0.0383) and facial rash (p=0.0398) at onset were less likely to developed M-ILD.Conclusion:ILD occurs in about one third of patients with IIM, mostly affected by ARS. The presence of anti-Ro antibodies as well as polyarthritis and dyspnea at onset predict the development of ILD.Disclosure of Interests:None declared

Anti-Ro52 antibodies are a risk factor for interstitial lung disease in primary Sjögren syndrome.

To determine whether anti-Ro52 antibodies are associated with ILD in pSS. Retrospective study based on the presence or absence of anti-Ro52 antibodies in patients with pSS. Patients underwent chest HRCT at the time of diagnosis or during follow-up. Sixty-eight patients were included. Two groups were defined by the presence (n=31) or absence (n=37) of anti-Ro52 antibodies. ILD was significantly higher in the presence of anti-Ro52 (41.9%, n=13) versus in the anti-Ro52-negative group (16.2%, n=6; p=0.019). Multivariate analysis adjusted for anti-SSA/Ro60, anti-SSB antibodies and rheumatoid factor status confirmed that anti-Ro52 antibodies positivity is a predictive factor for ILD (p=0.01). Nonspecific interstitial pneumonia was the most common pattern of ILD (31.6%). The majority of patients were diagnosed with pSS simultaneously to ILD (52.6%). In the anti-Ro52-negative group, no patients develop ILD after 5 years of follow-up. In pSS, the risk of developing ILD is higher in the presence of anti-Ro52 antibodies. In patients with pSS and anti-Ro52 antibodies, a clinical screening and pulmonary functional tests with DLCO is necessary during the follow-up and should comprise chest HRCT if there is a decline in the DLCO or clinical symptoms or inspiratory crackles.

462 Systemic fluorouracil causing subacute cutaneous lupus erythematosus

Case History: A 67-year-old woman with pancreatic adenocarcinoma presented with photosensitivity and pruritic photodistributed annular plaques over the bilateral extensor forearms and dorsal hands after her fourth cycle of FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin). Dermatopathology showed an interface dermatitis with a cuffed perivascular lymphocytic infiltrate and dermal mucin, suggestive of lupus erythematosus. Laboratory evaluation demonstrated an antinuclear antibody level of 8.0 U, anti-Ro IgG > 8.0 U, and anti-La IgG > 8.0 U. Systemic lupus was excluded given the lack of systemic symptoms, normal renal function, and normal urine studies. She was diagnosed with subacute cutaneous lupus erythematosus (SCLE) thought to be induced by systemic fluorouracil. Treatment and Follow-up: Photoprotection was advised, and she was treated with topical steroids while receiving three additional chemotherapy cycles. The eruption progressed to involve her back and chest and pruritus worsened, prompting cessation of fluorouracil from her treatment regimen. Five weeks after discontinuation of fluorouracil and while still receiving folinic acid, irinotecan, and oxaliplatin, the cutaneous eruption and associated pruritus resolved. Discussion: Drug-induced SCLE is most commonly associated with thiazides, terbinafine, calcium channel blockers, and angiotensin-converting enzyme inhibitors. Although several reports describe capecitabine, an oral fluorouracil prodrug, causing SCLE, only two descriptions of fluorouracil-induced SCLE exist in the literature. The pathophysiology underlying SCLE caused by fluorouracil is unclear although it has been postulated that fluorouracil preferentially targets epidermal basal cells leading to increased ultraviolet light-induced damage. The presence of anti-Ro antibody may also predispose individuals to fluorouracil-associated lupus erythematosus-like eruptions. Given the widespread use of fluorouracil and its prodrugs in oncologic management, both oncologists and dermatologists should be aware of the possibility of fluorouracil-induced SCLE.

Drug-induced Rowell syndrome, a rare and difficult to manage disease: A case report.

Rowell syndrome is defined as the association between lupus erythematosus, erythema multiforme-like lesions and characteristic immunological changes including positive tests for rheumatoid factor, speckled antinuclear antibody, positive anti-Ro or anti-La antibodies. The present report presents the case of a 45-year-old female patient who was previously diagnosed in January 2010 with terbinafine-induced subacute cutaneous lupus erythematosus and was admitted for a skin eruption consisting of erythematous-papular erythema multiforme-like lesions, primarily on the trunk and limbs. The associated symptoms consisted of fatigability, myalgia and gonalgia. In October 2015, the illness reoccurred ~1 week after the initiation of Helicobacter pylori eradication treatment. Anti-Ro antibodies, rheumatoid factor and antinuclear antibody tests were positive. Given the patient's medical history, clinical manifestations, and laboratory, histopathological and immunofluorescence microscopy findings, a diagnosis of Rowell syndrome was made. Systemic corticosteroids (methylprednisolone; 0.5 mg/kg/day) and immunomodulatory therapy (azathioprine; 50 mg/day) were administered with the associated medication (omeprazole, 20 mg/day; KCl, 1 g/day) and topical dermocorticoids (fluticasone propionate 0.05% cream; 1 application/day), with a favorable outcome. The major diagnostic criteria for Rowell syndrome are the presence of lupus erythematosus (acute, subacute or systemic), erythema multiforme-like lesions and positive testing for antinuclear antibodies. The minor diagnostic criteria for Rowell syndrome are chilblains, the presence of anti-Ro antibodies and positive testing for rheumatoid factor. A diagnosis of Rowell syndrome is made if the patient exhibits all major criteria and at least one minor criterion. The present case met all diagnostic criteria, excluding the presence of chilblains. Notably, in this case there was a co-occurrence of subacute lupus erythematosus and Rowell syndrome lesions, which was drug-induced.

Progression and mortality of interstitial lung disease in mixed connective tissue disease: a long-term observational nationwide cohort study.

To assess the prevalence, extent, progression, functional impact and mortality of interstitial lung disease (ILD) in a nationwide unselected MCTD cohort. The study cohort included patients with high-resolution CT lung scans available at baseline (n = 135) and at follow-up (n = 119). The extent of disease was expressed as percentage of total lung volume (TLV). ILD was present in 41% of MCTD patients at follow-up. Median (interquartile) extent (% of TLV) was 5 (8) at baseline and 7 (17) at follow-up, mean length 6.4 years later. The lung disease progressed in 19% of patients across the observation period. Predictors of ILD progression were elevated anti-RNP titre [hazard ratio (HR) 1.5, 95% CI: 1.1, 2.0; P = 0.008], presence of anti-ro52 antibodies (HR = 3.5, 95% CI: 1.2, 10.2; P = 0.023), absence of arthritis (HR = 0.2, 95% CI: 0.1, 0.6; P = 0.004) and male gender (HR = 4.0, 95% CI: 1.4, 11.5; P = 0.011) after age and baseline disease adjustments. The risk of death increased by 2.9 (95% CI: 1.1, 7.9; P = 0.038) in patients where disease involved ⩾5% of TLV. Lung disease extent and progression in MCTD are modest. Yet, the extension continues several years after MCTD diagnosis causing lung function decline and increasing the risk of mortality. The study identified male gender, elevated anti-RNP titre, presence of anti-ro52 antibodies and absence of arthritis as the strongest predictors of ILD progression.

TNF-308 G/A polymorphism and risk of systemic lupus erythematosus in the Polish population

Objectives. Numerous studies have been performed with TNF-α-308 G/A (rs1800629) single nuclear polymorphism (SNP) to evaluate the risk of SLE in various ethnicities. However, the significance of TNF-α-308 G/A in both clinical and laboratory studies of the disease remains unclear.Methods. Using a high-resolution melting curve analysis, we assessed the prevalence of TNF-α-308 G/A SNP in SLE patients (n = 262) and controls (n = 528) in a Polish population. We also assessed the contribution of this SNP to various clinical symptoms and the presence of autoantibodies in SLE patients.Results. The p-value obtained using a χ2 test for the trend of TNF-α-308 G/A was statistically significant (ptrend = 0.0297). However, using logistic regression analysis for the presence of the HLA-DRB1*03:01 haplotype, we observed that the TNF-α-308 G/A SNP may be the DRB1*03:01-dependent risk factor of SLE in the Polish population. There was a significant contribution of TNF-α-308 A/A and A/G genotypes to arthritis OR = [2.692 (1.503–4.822, p = 0.0007, pcorr = 0.0119)] as well as renal SLE manifestation OR = [2.632 (1.575–4.397, p = 0.0002, pcorr = 0.0034)]. There was a significant association between TNF-α-308 A/A and A/G genotypes and the presence of anti-Ro antibodies (Ab) OR = 3.375(1.711–6.658, p = 0.0003, pcorr = 0.0051). However, the logistic regression analysis revealed that only renal manifestations and the presence of anti-anti-Ro antibodies remained significant after adjustment to the presence of the HLA-DRB1*03:01 haplotype.Conclusion. Our studies indicate that the TNF-α-308 G/A polymorphism may be a DRB1*03:01 haplotype-dependent genetic risk factor for SLE. However, this SNP was independently associated with renal manifestations and production of anti-Ro Ab.

Clinical presentations and molecular basis of complement C1R mutation in a large turkish family

Inherited deficiencies of complement components can result in autoimmunity. Early age of onset, prominent cutaneous manifestations, and presence of anti-Ro antibodies are features suggestive of a complement deficiency. SLE-associated deficiencies in subcomponents of the C1 complex, C1r and/or C1s, were described 4 decades ago, however the molecular basis and functional aspects of the complement deficiency have not been clearly determined.

Anti-Ro52 Antibodies and Interstitial Lung Disease in Connective Tissue Diseases Excluding Scleroderma

Introduction. The presence of anti-Ro52 antibodies has been reported in a wide variety of autoimmune diseases, particularly in myositis, scleroderma, and autoimmune liver diseases. Clinical significance of anti-Ro52 antibodies remains controversial, and studies are lacking for clarifying the association of anti-Ro52 with interstitial lung disease (ILD) in connective tissue diseases (CTD). Objectives. To determine if anti-Ro52 antibodies are associated with ILD in CTD other than scleroderma. Methods. Single-center, retrospective study based on immunoblotting panel analysis and patients clinical records. Results. In our connective tissue disease cohort, 162 patients had immunoblotting panels with anti-Ro52 reactivity analysis, 41 (25,3%) had inclusion criteria. Among the 41 selected sera, 85.4% (n = 35) had anti-Ro52 reactivity. The prevalence of ILD in the positive anti-Ro52 antibodies was 71.4% (n = 25), and 16.7% (n = 1) in the negative anti-Ro52 group (P = 0.018). Overall sensitivity (96.2%), specificity (83.3%), positive (71.4%) and negative (83.3%) predictive values of anti-Ro52 antibodies to determine ILD in CTD is detailed in this study. Conclusion. Ro52 autoantibodies are associated with ILD in CTD excluding scleroderma. We suggest that the presence of anti-Ro52 reactivity in CTD should increase the clinician curiosity for the search of ILD.

Letter to the Editor Subacute cutaneous lupus erythematosus due to proton pump inhibitor intake: and literature review

Letter to the Editor Subacute cutaneous lupus erythematosus due to proton pump inhibitor intake: and literature review

Are Anti-Ro52 Antibodies Associated with Pulmonary Involvement in Scleroderma?

Introduction: The presence of anti-Ro52 antibodies has been reported in a wide variety of autoimmune diseases, particularly in myositis, scleroderma and autoimmune liver diseases. Clinical significance of anti-Ro52 antibodies remains controversial. Studies are lacking in clarifying the association of anti-Ro52 with pulmonary involvement in scleroderma. Objectives: To determine if anti-Ro52 antibodies are associated with pulmonary involvement (interstitial, indirect pulmonary hypertension, or both) in scleroderma. Methods: Single center, retrospective study based on immunoblotting panel analysis and patients clinical records. Pulmonary manifestations were sub-grouped in: 1) interstitial (alveolitis and/or fibrosis), 2) pulmonary artery systolic pressure (PASP) ≥40 mmHg plus interstitial pulmonary disease, and 3) isolated PASP≥40 mmHg (purely vascular). Results: Our scleroderma cohort included 200 patients, of which 137 had immunoblotting panels with anti-Ro52 reactivity analysis. The search was conducted between January 2010 and July 2011. The frequency of pulmonary manifestations in patients with positive anti-Ro52 antibodies was 67.7% (n=31), and 60% (n=24) in the negative anti-Ro52 group, showing no significant differences between groups (p=0.621). Still no significant differences were found when pulmonary manifestations were evaluated according to the subgroups (p=0.525). Sensitivity, specificity, positive and negative predictive values of anti-Ro52 reactivity for determining pulmonary involvement in scleroderma were low. Conclusion: No association was found between positive anti-Ro52 antibodies and pulmonary involvement in scleroderma. *Corresponding author: Joao Pedro Ferreira, Unidade de Imunologia Clinica, Hospital de Santo Antonio, Centro Hospitalar do Porto, Porto, Portugal, E-mail: jp7ferreira@hotmail.com Received January 04, 2012; Accepted March 13, 2012; Published March 15, 2012 Citation: Ferreira JP, Almeida I, Marinho A, Cerveira C, Vasconcelos C (2012) Are Anti-Ro52 Antibodies Associated with Pulmonary Involvement in Scleroderma?. J Pulmonar Respirat Med 2:116. doi:10.4172/2161-105X.100011 Copyright: © 2012 Ferreira JP, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The use of C3d and C4d immunohistochemistry on formalin-fixed tissue as a diagnostic adjunct in the assessment of inflammatory skin disease

Direct immunofluorescent (DIF) testing defines an important diagnostic adjunct in the classification of various inflammatory skin conditions; it requires fresh tissue, a laboratory equipped to perform the procedure, and a pathologist skilled in its interpretation. Although advances have been made in the development of antibodies that can be applied to paraffin-embedded tissue, there has been no reported success on the application of paraffin tissue-based immunohistochemistry as a potential substitute for DIF testing on skin biopsy material. We applied C3d and C4d immunohistochemistry on paraffin-embedded, formalin-fixed tissue to define a potential application of these two antibodies as a diagnostic adjunct in the evaluation of various inflammatory skin diseases. A natural language search identified cases submitted for both light microscopic and DIF studies from July 2006 to August 2007. We prospectively included similar cases encountered from August 2007 to March 2008. We correlated the C3d and C4d staining pattern with the DIF and light microscopic findings. All cases of scarring discoid lupus erythematosus (LE) (20/20) and systemic LE (5/5) showed prominent granular C3d along the dermoepidermal junction (DEJ) and a positive lupus band test result in the latter by DIF. All systemic LE cases demonstrated granular DEJ C4d with C3d or C4d in blood vessels (BV). There was a negative lupus band test result without DEJ C3d or C4d in all cases of subacute cutaneous lupus erythematosus (SCLE) (15/15). There were, however, deposits of C4d within epidermal keratinocytes (7/7), corresponding to IgG decoration of keratinocytes by DIF and the presence of anti-Ro antibodies. Dermatomyositis cases showed prominent mural C3d and C4d in BV corresponding to C5b-9 by DIF (12/12) and one case of hydroxyurea-induced dermatomyositis lacked this staining. Although by DIF all dermatomyositis cases had a negative lupus band test result, 25% of cases showed staining for C3d along the DEJ (3/9). Bullous pemphigoid cases demonstrated homogenous DEJ C3d (17/17) whereas C4d was characteristically negative; there was 100% concordance with linear IgG and C3d by DIF. Eighty two percent of pemphigus cases demonstrated prominent intercellular C3d and C4d, roughly mirroring the intercellular pattern for IgG and complement seen by DIF (9/11). Porphyria cases showed homogeneous and granular C3d (11/11) and C4d (7/11), mirroring the vascular immunoglobulin and C5b-9 by DIF. All cases of urticarial (5), leukocytoclastic (6), and lymphocytic (1) vasculitis exhibited prominent mural C3d and C4d in BV, whereas Henoch-Schönlein purpura (10/10) showed primarily mural BV C3d without C4d, with IgA by DIF. Three cases of relapsing polychondritis showed C3d and C4d within chondrocyte nuclei (3/3), in contrast to negative staining in chondrodermatitis nodularis helicis (0/2). Hypersensitivity reactions were negative for C3d and C4d. The small sample size in each category is a limitation. The lack of literature precedent with regard to immunohistochemical assessment of extracellular antigens on paraffin-embedded tissue in skin samples is another limitation of this study. When correlated with the light microscopic and clinical findings, the C3d and C4d assay has significant application in the assessment of select inflammatory skin diseases including vasculopathic conditions, collagen vascular disease, and autoimmune vesiculobullous disorder. It may prompt further DIF testing or, in some instances, may even define a reasonable substitute for DIF and/or add to the morphologic assessment of a biopsy specimen submitted for routine light microscopic assessment primarily in the setting of autoimmune vesiculobullous disease and collagen vascular disease.

Severe Lupus Nephritis

This study assessed whether certain clinicopathologic variables could explain the impact of race on outcome in 86 patients who had severe lupus nephritis and were available for long-term follow-up after participating in a prospective, controlled, clinical trial. Fifty-four (63%) patients were white, 21 (24%) were black, and 11 (13%) were categorized as other. The proportion of patients with anti-Ro, anti-nRNP, and anti-Sm was significantly greater among black patients. Biopsies with segmental active proliferative and necrotizing lesions that involved >or=50% of glomeruli +/- membranous glomerulonephritis (class III >or=50%+/-V) were significantly more common (white 44%, black 76%, other 36%; P < 0.05) and diffuse proliferative glomerulonephritis +/- membranous glomerulonephritis (class IV+/-V) was less common (white 54%, black 24%, other 64%) among black patients. Attainment of a remission was greatest among white patients (white 52%, black 29%, other 27%; P = 0.09). Features that were predictive of a remission were white race, baseline serum creatinine, and class IV+/-V lesions. Patient survival at 10 yr (white 81%, black 59%, other 73%; P = 0.029) and renal survival at 10 yr (white 68%, black 38%, other 61%; P = 0.015) were significantly poorer in black patients. Predictors of ESRD were serum creatinine, the presence of anti-Ro antibodies, class III >or=50%+/-V lesions, and failure to achieve a remission. In conclusion, racial differences were observed in the serologic and histologic features at presentation, response to treatment, and outcome of patients with severe lupus nephritis. In a population of patients with severe lupus nephritis, black patients were significantly more likely to have a serologic profile and renal lesions that were associated with more aggressive renal disease and resulted in worse outcomes than white patients.

Antiphospholipid antibodies and antiphospholipid syndrome in 57 children and adolescents with systemic lupus erythematosus.

The presence of antiphospholipid (aPL) antibodies and antiphospholipid syndrome (APS) was researched in 57 children and adolescents with systemic lupus erythematosus (SLE). The frequency of aPL antibodies was 75.4% (anticardiolipin 70.2% and lupus anticoagulant 29.1%). The positivity for these antibodies fluctuated during the course of the disease. No association was found between aPL antibodies and clinical or laboratory manifestations or the autoantibodies studied, nor with the activity or gravity of the SLE. APS was diagnosed in 14% of the cases (eight patients), on average three years after the diagnosis of SLE. Four patients had arterial thrombosis (stroke, three; transient ischaemic attack, one; amaurosis fugax, two; renal, one), one presented with deep vein thrombosis (DVT) and three had involvement of small calibre vessels (osteonecrosis, two; transverse myelitis, one). Recurrences were observed in three of the eight cases (37.5%), with a mean interval of 13 months between the events. The presence of APS was associated with haemolytic anaemia, leukopenia, thrombocytopenia, coagulation abnormalities, ischaemic cerebrovascular accidents, amaurosis fugax, osteonecrosis and interstitial pneumonitis. A negative association was observed between APS and the presence of anti-Ro antibodies.

Hepatitis autoinmune y anticuerpos anti-Ro positivos. ¿Alguna relación?

Antinuclear antibodies (ANA) are considered to be markers of autoimmune disease. Several specific reactivities of ANA are known, among them the Ro (SS-a) complex. Although the presence of anti-Ro antibodies is widely known in systemic connective tissue diseases such as lupus erythematous or Sjögren's syndrome, few studies have attempted to link this finding with autoimmune hepatitis (AIH). We present a case of acute AIH in a 55-year-old woman who tested positive for anti-Ro 60 kD antibodies. The Ro (SS-A) antigen is a complex ribonucleoprotein whose structure is still the subject of debate. Two fractions, of 50 and 60 kD, have been identified. A review of the literature revealed frequencies of 21-34% for anti-Ro 52 kD and of 9-13-6% for anti-Ro 60 kD in AIH. Although no relationship has been demonstrated between this complex and the etiopathogenic mechanisms or clinical patterns of AIH, we propose that multicenter investigations with large series should be performed before the possible involvement of anti-Ro antibodies in these diseases is definitively ruled out.

Factors predictive of outcome in severe lupus nephritis

In 1992, we published the results of a prospective, controlled trial of aggressive therapy (high-dose prednisone plus oral cyclophosphamide alone or with plasmapheresis) in 86 patients with severe lupus nephritis. During this study, remission (serum creatinine ≤1.4 mg/dL [≤123 μmol/L] and proteinuria ≤330 mg/d of protein) in renal disease occurred in 37 patients (43%). To assess the long-term effect of remission on patient and renal survival, we now report the results of our extended follow-up of these patients. After an average of 10 years of follow-up in the 86 patients, patient survival rates at both 5 and 10 years were 95% in the group that had a remission and 69% at 5 years and 60% at 10 years in the no-remission group (P < 0.001). Renal survival rates were 94% at both 5 and 10 years in the remission group compared with 46% at 5 years and 31% at 10 years in the no-remission group (P < 0.0001). Features predictive of remission included stable renal function after 4 weeks on therapy, category IV lesion, lower chronicity index, white race, lower urine protein excretion level at baseline, and lower baseline serum creatinine level. The features predictive of end-stage renal disease were higher baseline serum creatinine level, presence of anti-Ro antibodies, and failure to attain a remission. Thus, in patients with the most severe forms of lupus nephritis, a remission of clinical renal abnormalities is associated with dramatic improvement in long-term patient and renal survival.

Long-term outcome of mothers of children with complete congenital heart block

To determine the health of mothers of offspring with complete congenital heart block (CHB) both at the time of delivery of the affected child and in the long-term, and the percentage of mothers and children with CHB who had anti-SSA/Ro and/or SSB/La antibodies. Sixty-four mothers of 64 children with CHB (seen between 1964 and 1993) were identified through the Cardiology database of The Hospital for Sick Children, Toronto, Canada. Medical information from these of children with CHB was evaluated. Data were obtained from the mothers by mailed questionnaire, telephone interview, and/or from the attending physicians. The presence of anti-Ro antibodies and anti-La antibodies were evaluated by ELISA assay. The mean age at the time of delivery of the first child with CHB was 28 +/- 6 years. At the time of delivery 42 (66%) mothers were healthy, 2 (3%) had systemic lupus erythematosus (SLE), 2 (3%) had linear scleroderma, 2 (3%) had rheumatoid arthritis; 3 (5%) had a history of rheumatic fever (but were otherwise well), 1 (2%) had Sjogren's syndrome (SS), and 12 (19%) had an undifferentiated autoimmune syndrome (UAS) (arthralgia, myalgia, photosensitivity, skin vasculitis, Raynaud's phenomenon). The mean time to follow-up from deliver to study was 121 +/- 88 months. The mean maternal age at study was 38 +/- 9 years. Three of 12 mothers who initially had a UAS progressed to SLE (average follow-up time of 80 months, median 96), and 2 developed SS (with average follow-up time 140 months, median 132) and 1 went into remission. The mean follow-up time for the other mothers who did not develop an autoimmune disease was 150 +/- 102 months. Thirty-six of the 42 initially healthy mothers remained well. One mother developed SLE; 1 developed hyperthyroidism; 1 developed anky-losing spondylitis; and 3 developed an UAS. The mean follow-up time of the 36 mothers who remained healthy was similar (123 +/- 97 months) to the 6 initial healthy mothers who developed an autoimmune disease (121 +/- 36 months). Anti-Ro and/or anti-La antibodies were positive in 32 of 53 (60%) mothers tested. Fourteen of the 53 mothers were symptomatic at the time of delivery and 39 were asymptomatic. Anti-Ro and/or anti-La antibodies were positive in 12 of 13 mothers tested at the time of delivery. The long-term maternal outcome in our cohort was very good as most of the initially healthy mothers remained well at follow-up. Twenty-five percent of the mothers with a UAS and only 2% of the initially healthy mothers developed SLE. The development of an autoimmune disease in an asymptomatic mother identified by the birth of a child with CHB was less common in our study than in previous studies. However, close follow-up of mothers with UAS is warranted.