anti-U1RNP Research Articles

A Case Report of Mixed Connective Tissue Disease Predominantly Manifesting as Systemic Sclerosis in a Middle-Aged Nepali Woman

Introduction: Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disorder, first described in 1972, that presents with overlapping features of systemic lupus erythematosus, systemic sclerosis, and polymyositis. The diagnosis of MCTD is complex and often delayed due to its varied clinical manifestations and the requirement of serological confirmation, particularly the presence of anti-U1 RNP antibodies. Despite its global prevalence, data on MCTD are limited, especially in the South Asian population.  Case Report: We present the case of a 42-year-old Nepali woman with a decade-long history of myalgia, muscle weakness, and joint pain, initially misdiagnosed as rheumatoid arthritis. Over time, she developed Raynaud phenomenon, dysphagia, and progressive muscle weakness, which prompted further investigation. Serological testing revealed elevated levels of anti-U1 RNP antibodies and a positive antinuclear antibody (ANA) titer, confirming the diagnosis of MCTD according to the Alarcón-Segovia criteria. The patient was successfully managed with a regimen of corticosteroids, hydroxychloroquine, and nifedipine, resulting in significant symptomatic improvement.  Discussion: This case underscores the diagnostic challenges associated with MCTD, a condition that may present with nonspecific symptoms and mimic other rheumatic diseases. The prolonged diagnostic journey of this patient highlights the need for heightened clinical suspicion and comprehensive serological testing in patients with overlapping connective tissue disease features. Furthermore, the case contributes to the limited body of literature on MCTD in the South Asian population, emphasizing the importance of early recognition and tailored management strategies to improve patient outcomes.  Conclusion: MCTD is a complex and under-recognized autoimmune disorder, particularly in the South Asian context. This case report highlights the importance of considering MCTD in the differential diagnosis of patients with multi-systemic involvement and underscores the role of serological testing in confirming the diagnosis. Early diagnosis and appropriate management are crucial in mitigating disease progression and improving the quality of life for patients with MCTD.

The study of anti-idiotype antibody and antinuclear antibodies (ANA) in people receiving three doses of the COVID-19 vaccine

The study of anti-idiotype antibody and antinuclear antibodies (ANA) in people receiving three doses of the COVID-19 vaccine

A rare case of anti U3 RNP scleroderma presenting as limb girdle muscle weakeness

A rare case of anti U3 RNP scleroderma presenting as limb girdle muscle weakeness

Nailfold capillaroscopy in Egyptian systemic lupus erythematosus (SLE) patients: correlation with demographic features and serum levels of IL 17A and IFNs I

BackgroundIn SLE patients, cytokines are linked to endothelial cell damage. Nailfold capillaroscopy (NFC) is a simple method for evaluating micro-vascular abnormalities in different connective tissue diseases (CTDs). The study aimed to detect the levels of interleukin 17A (IL 17A), type I interferons (IFNs I) in the serum, and NFC changes in Egyptian SLE patients compared to a control group and to correlate NFC findings with patients’ demographic features and serum levels of IL 17A and IFNs I.ResultsSerum levels of IL 17A, IFN α, and IFN β were significantly higher in SLE patients than in control group (P < 0.0001). About thirty nine patients (73.6%) of the 53 SLE patients showed abnormal NFC changes. Egyptian SLE patients had a high prevalence of the NFC non-specific pattern, with 32 (60.4%) patients showing non-specific changes and 7 (13.2%) patients showing scleroderma pattern, including 3 (5.6%) patients with active scleroderma pattern and 4 (7.55%) patients with late scleroderma pattern. Furthermore, Raynaud’s phenomenon (RP) was observed in 8 (15.1%) SLE patients, with 3 (5.6%) having normal NFC pattern and 5 (9.4%) having scleroderma pattern. All controls (n = 20) showed normal hairpin shape capillaries. Except for SLEDAI (P = 0.03) and the presence of RP (P < 0.0001), there were no significant differences in demographic and laboratory parameters between the three NFC patterns (normal, non-specific, and scleroderma); additionally, NFC score correlated significantly with SLEDAI (P = 0.021).ConclusionAs a result of the high disease activity, Egyptian SLE patients had elevated serum levels of IL 17A and IFNs I. The most common NFC pattern in Egyptian SLE patients was a non-specific pattern. NFC abnormalities in Egyptian SLE patients were correlated with disease activity but not with patients’ ages, disease duration, or serum levels of IL 17A and IFNs I. SLE patients with scleroderma NFC pattern and RP should be closely followed for the possibility of appearance of anti-U1 RNP antibodies and MCTDS.

Autoantibodies against the NineTeen complex and U5 RNP in systemic sclerosis

ObjectiveMultiple spliceosome components are known autoantigens in systemic sclerosis (SSc). Here we aim to identify new and characterize rare anti-spliceosomal autoantibodies in patients with SSc without known autoantibody specificity.MethodsSera that precipitated spliceosome subcomplexes, as detected by immunoprecipitation-mass spectrometry (IP-MS), were identified from a database of 106 patients with SSc without known autoantibody specificity. New autoantibody specificities were confirmed with immunoprecipitation-western blot. The IP-MS pattern of new anti-spliceosomal autoantibodies was compared with anti-U1 RNP-positive sera of patients with different systemic autoimmune rheumatic diseases and anti-SmD-positive sera of patients with systemic lupus erythematosus (n = 24).ResultsThe NineTeen Complex (NTC) was identified and confirmed as new spliceosomal autoantigen in one patient with SSc. U5 RNP, as well as additional splicing factors, were precipitated by the serum of another patient with SSc. The IP-MS patterns of anti-NTC and anti-U5 RNP autoantibodies were distinct from those of anti-U1 RNP- and anti-SmD-positive sera. Furthermore, there was no difference in IP-MS patterns between a limited number of anti-U1 RNP-positive sera of patients with different systemic autoimmune rheumatic diseases.ConclusionAnti-NTC autoantibodies are a new anti-spliceosomal autoantibody specificity, here first identified in a patient with SSc. Anti-U5 RNP autoantibodies are a distinct but rare anti-spliceosomal autoantibody specificity. All major spliceosomal subcomplexes have now been described as target of autoantibodies in systemic autoimmune diseases.

A Comparative Study of Mixed Connective Tissue Disease and Overlap Syndromes – A Single-Center Study from India

Introduction: Mixed connective tissue disease (MCTD) a classical overlap syndrome with four different defining criteria. The present study attempts to compare the clinical features and autoantibodies for MCTD and overlap syndromes. Methods: In this observational study from October 2018 to August 2020, we included all the patients of MCTD and overlap syndromes. Alarcon–Segovia criteria was used as defining criteria for MCTD patients while the patients meeting diagnostic criteria for more than 1 of 6 classical autoimmune rheumatic diseases were selected in the overlap syndromes group. We compared their clinical features, laboratory parameters, and autoantibody profiles. MS Excel, STATA were used for statistical analysis, and comparison between the groups was done with t-test, Chi-square test, and Wilcoxon rank sum test. P &lt; 0.05 was considered as statistically significant. Results: The study consisted of 60 consecutive patients (MCTD, n = 30 and overlap syndromes, n = 30) with higher female population in both groups (90% in MCTD and 84% in the overlap syndromes group) compared to males. The incidence of fever (83.3% vs. 46.6%), weight loss (60% vs. 26.6%), trigeminal neuralgia (76.6% vs. 13.3%), and myositis (63.3% vs. 20.0%) was significantly higher in MCTD than overlap syndromes whereas the incidence of cough (66.6% vs. 90.0%) and dry mouth (20.0% vs. 53.3%) was higher in overlap syndromes than MCTD (P &lt; 0.05). Anti-U1 RNP antibodies were seen in all MCTD (100.0%) patients while anti-Scl 70 antibodies (60%) and anti-ribosomal-p-protein antibodies (13.3%) were seen in overlap syndromes. Conclusion: Fever and weight loss, trigeminal neuralgia, and myositis were more common in MCTD than overlap syndromes. Anti-U1 RNP antibodies seen in MCTD while Anti-Scl 70 antibodies and anti-ribosomal-P antibodies were commonly were seen in overlap syndromes.

Unusual Presentation of PLA2G6-Related Neurodegeneration with Retinal Vasculitis.

Unusual Presentation of PLA2G6-Related Neurodegeneration with Retinal Vasculitis.

Quantification of Antifibrillarin (anti-U3 RNP) Antibodies: A New Insight for Patients with Systemic Sclerosis.

Background: The detection of additional autoantibodies is of great concern in systemic sclerosis (SSc) when those included in the ACR/EULAR classification are negative. In this context, the interest of antifibrillarin (anti-U3RNP) autoantibodies (AFAs) in the routine evaluation of SSc remains unclear. We aimed to assess the relevance of AFAs and their clinical association in SSc patients. Methods: In a multicenter observational retrospective study, we collected immunological and clinical data associated with AFA positivity in SSc (n = 42) and non-SSc patients (n = 13). Patients with SSc negative for AFAs (n = 83) were considered as a control group. AFAs were detected by indirect immunofluorescence (IIF) using HEp-2 cells, EliA or immunoblot techniques. Results: We confirmed a typical nuclear IIF pattern and showed that AFAs are mostly exclusive towards SSc conventional autoantibodies. Although also observed in non-SSc patients, high levels of AFAs with the ELiA technique allowed the diagnosis of SSc. Compared to AFA-negative SSc patients, AFA-positive SSc patients more frequently exhibited visceral involvements. They more frequently suffered from the diffuse cutaneous form and had a higher global severity of the disease. Conclusions: We demonstrate the usefulness of quantifying AFAs in the immunological exploration of SSc, especially when patients are seronegative for SSc conventional autoantibodies and display a typical IIF pattern. AFAs might constitute an interesting marker of SSc severity.

Demographic characteristics and clinical manifestations of interstitial lung disease with systemic sclerosis in eastern part of Libya

Abstract Introduction: Pulmonary involvement, such as Interstitial Lung Disease (ILD) and Pulmonary Hypertension (PH ), accounts for significant morbidity and is the leading cause of Systemic sclerosis (SSc)-related morbidity and mortality. The aim of the current study was to study the frequency of occurrence of ILD in SSc and to describe the clinical and radiological picture of pulmonary involvement in SSc. Patients and Methods: Forty patients attending different rheumatology clinics in eastern part of Libya between January 2018 and September 2020 were included. Basic details including age, gender, disease duration, detailed history, and clinical examination were noted. Autoimmune profiling included rheumatoid factor, antinuclear antibodies, and anti-Scl-70 antibodies. Pulmonary function test, chest X-ray (CXR), and high-resolution computed tomography of the chest (HRCT) in all patients were recorded. Data presented either as frequencies and percentages or as means ± standard deviation. Results: The male: female ratio was 1:9 with a mean age of 37.5 ± 9.6 years and duration of illness 6 ± 4 years. diffuse cutaneous SSc was seen in 62.5% of the patients. 77.5% of the participants had bilateral crepitation and 57.5% had loud P2. Presenting complaints included gastrointestinal reflux in 72.5%, digitalis ulcerations in 40%, and synovitis/arthritis of all patients. Other comorbidities included congestive heart failure in 12.5%, PH in 15%, and renal impairments in 7.5% of all patients. Anti-Scl-70 antibody was the most common in all patients (45%), followed by anti-centromere Ab (25%), anti-U3 RNP (10%), and anti-U1 RNP (5%). 72.5% of the participants had reticulonodular shadows on CXR. HRCT showed honeycombing as the predominant finding (37.5%). Echocardiograms showed that 15% of all patients have signs of PH. Duration of disease, dyspnea, cough, bilateral crepitations, and CXR were found to be significantly associated with extensive ILD (P &lt; 0.05). Conclusion: ILD is a serious complication of SSc, it is more common among patients with dcSSc. Chest HRCT is very sensitive to detect ILD. A significant association was found in Libyan patients between the severity of ILD and the duration of disease, dyspnea, cough, bilateral crepts, and CXR.

Mixed Connective Tissue Disease- Physician’s Dilemma: A case report

Mixed connective tissue disease is an entity of autoimmune disease with overlapping features of systemic lupus erythematosus, scleroderma, rheumatoid arthritis, dermatomyositis and with positive anti-U1 RNP antibody. We report here a 52 year old non-diabetic, normotensive woman presenting with new onset dysphagia for two months with variable features of multiple types of connective tissue diseases for two years. Clinical features and type specific serological tests for different connective tissue diseases showed puzzling results. However, finally a high titer of anti-U1RNP antibody led to the diagnosis of mixed connective tissue disease.

MULTIFOCAL PULMONARY NODULAR HYPERPLASIA IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare lympho-proliferative disorder characterized by benign polyclonal lymphoid proliferation. We describe a case of a 44-year-old woman with biopsy proven multifocal pulmonary nodular lymphoid hyperplasia in the setting of SLE. CASE PRESENTATION: 44-year-old woman presented to the emergency room with complaints of intermittent pleuritic chest pain and exertional dyspnea for 3 months. Review of systems was positive for joint pains and morning stiffness. Physical examination was remarkable for tenderness and swelling at proximal interphalangeal joints. Cardiac work up including electrocardiogram, troponin levels and echocardiogram was unremarkable. CT scan of chest with contrast showed numerous bilateral cavitary ground glass opacities measuring about 1-2 cm in size. Transbronchial biopsy was non-diagnostic. A subsequent video-assisted thoracoscopic surgical biopsy revealed nodular lymphoid hyperplasia. Specimen was negative for malignancy, granulomatous disease or vasculitis. Lymphoma was also ruled out by flow cytometry. AFB, fungal and bacterial stains and cultures were negative. Hepatitis panel and HIV testing was negative. Rheumatologic work up showed negative rheumatoid factor and positive ANA, anti-SSA, anti-dsDNA Ab, anti smith and anti-U1-RNP antibodies. Inflammatory markers, ESR and CRP, were elevated. She was evaluated by rheumatology and further history revealed presence of alopecia and nasal sores in addition to serositis (pleuritis) and arthritis. Her clinical picture and serologies met the diagnostic criteria for SLE. DISCUSSION: Pulmonary lymphoid nodular hyperplasia is a rare benign lymphoproliferative disease. It is relatively more common in women and often an incidental finding on imaging. Most patients are asymptomatic, however symptoms such as cough, chest pain or dyspnea can be present. Diagnosis is made by surgical biopsy. It is essential to rule out malignancy, particularly mucosal associated lymphoid tissue lymphoma and infectious etiologies such as bacterial or fungal pulmonary infections. So far PNLH has been described in patients with Sjogren’s disease, without conclusive association. Most common pulmonary manifestation in SLE is pleurisy. Interstitial lung disease (ILD) is less common in SLE and is seen in patients who have anti–U1-RNP antibodies. Imaging findings are nonspecific; however, ground-glass opacities or consolidations may be present. PNLH has not been described in association to or as a manifestation of SLE in medical literature. There is paucity of data for correlation and larger studies are required to study this potential association. CONCLUSIONS: Pulmonary nodular lymphoid hyperplasia is a rare benign lymphoproliferative disorder. After malignancy and infectious etiology is ruled out autoimmune disease should be considered in patients with PNLH. Further work is warranted to establish this relation. Reference #1: Abbondanzo SL, Rush W, Bijwaard KE, Koss MN. Nodular lymphoid hyperplasia of the lung: a clinicopathologic study of 14 cases. Am J Surg Pathol. 2000;24(4):587–597. Reference #2: Song MK, Seol YM, Park YE, et al. Pulmonary nodular lymphoid hyperplasia associated with Sjögren's syndrome. Korean J Intern Med. 2007;22(3):192–196. doi:10.3904/kjim.2007.22.3.192. Reference #3: Quadrelli SA, Alvarez C, Arce SC, et al: Pulmonary involvement of systemic lupus erythematosus: analysis of 90 necropsies. Lupus 2009; 18: pp. 1053-1060 DISCLOSURES: No relevant relationships by William Han, source=Web Response No relevant relationships by Immad Munawar, source=Web Response No relevant relationships by Theresa Nicol, source=Web Response

Association of differentially expressed genes and autoantibody type in patients with systemic sclerosis.

The aims of this study were to investigate the relationship between the type of autoantibody and gene expression profile in skin lesions from patients with SSc, and to identify specific dysregulated pathways in SSc patients compared with healthy controls. Sixty-one patients with SSc from the Genetics vs Environment in Scleroderma Outcome Study cohort and 36 healthy controls were included in this study. Differentially expressed genes were extracted and functional enrichment and pathway analysis were conducted. Compared with healthy controls, lists containing 2, 71, 10, 144 and 78 differentially expressed genes were created for patients without specific autoantibody, ACA, anti-U1 RNP antibody (RNP), anti-RNA polymerase III antibody (RNAP) and anti-topoisomerase I antibody (ATA), respectively. While part of the enriched pathways overlapped, distinct pathways were identified except in those patients lacking specific autoantibody. The distinct enriched pathways included 'keratinocyte differentiation' for ACA, 'nuclear factor κB signalling' and 'cellular response to TGF-β stimulus' for RNAP, 'interferon α/β signalling' for RNP, and 'cellular response to stress' for ATA. Cell type signature score analysis revealed that macrophages/monocytes, endothelial cells and fibroblasts were associated with ACA, RNAP, ATA and the severity of the SSc skin lesions. Pathogenic pathways were identified according to the type of autoantibody by leveraging gene expression data of patients and controls from a multicentre cohort. The current study may promote the search for new therapeutic targets for SSc.

LUPUS: Trends of the disease in Northwest Punjab

Objectives: The aim of this study was to study the clinical profile of systemic lupus erythematosus (SLE) patients from a tertiary care center in Northwest Punjab. Materials and Methods: It was an observational cross-sectional study conducted at the Rheumatology Clinic, Adesh Hospital, Bathinda. Twenty-five patients classified to be suffering from SLE as per standard classification criteria (Systemic Lupus International Collaborating Clinics [SLICC]) were enrolled after obtaining consent for the same. Socio-demographic data, disease duration, disease activity, and treatment received were recorded. Analysis was performed for the various parameters. Results: The majority of patients (88%) were females with a female to male ratio of 7.3:1 with mean age of 30.5 years. Mucocutaneous involvement (92%) followed by musculoskeletal (84%). Nephritis was seen in 36%, deforming arthritis in 8%, and pleural involvement in 36% while ILD in 12%. Pericarditis was seen in 16%, and myocarditis was seen in 12%. Neurological involvement was seen in 36% patients with two cases of thrombotic CVA, one case of SAH and three cases of seizure disorder. Psychiatric symptoms were observed in 16% cases. AIHA was seen in 12%, leukopenia in 44%, and thrombocytopenia in 68%. Most common antibody was anti-dsDNA being present in 48% cases, followed by Anti Ro-60, Ro-52, Anti Sm, and Anti U1RNP antibody. Conclusion: We found a striking difference in the prevalence of pleuropulmonary features, neuropsychiatric features, Leukopenia, and thrombocytopenia in our subgroup of population as compared to the earlier studies from central and southern parts of India thus further emphasizing the fact that ethnic backgrounds predispose a patient for different phenotype.

Performance evaluation of a commercial line blot assay system for detection of myositis- and systemic sclerosis-related autoantibodies.

A line blot (LB) assay is a multi-analyte platform capable of simultaneously detecting multiple anti-nuclear antibody specificities. Here, we evaluated the performance of a commercial LB assay developed for the identification of myositis- or systemic sclerosis (SSc)-related autoantibodies (autoAbs). We screened 300 serum samples from patients with various connective tissue diseases using an LB assay and compared the results of myositis- or SSc-related autoAbs with those identified by RNA and protein immunoprecipitation (IP) assays or indirect immunofluorescence (IIF). The IP assays revealed anti-Jo-1 Abs in 14 patients, anti-EJ Abs in 12, anti-PL-7 Abs in 8, anti-PL-12 Abs in 4, anti-Mi-2 Abs in 6, anti-SRP Abs in 8, anti-topoisomerase I Abs in 54, anti-RNA polymerase III Abs in 24, anti-U3 RNP Abs in 9, anti-Th/To Abs in 9, anti-Ku Abs in 14 and anti-hUBF Abs in 4, whereas IIF identified anti-centromere in 35. Good agreement between the IP assays and the LB assay was found only for anti-Jo-1 and anti-centromere antibodies. When a cut-off was adjusted to reconcile with the results of IP assays, the detection performance of LB assay was improved for anti-EJ, anti-PL-7, anti-PL-12, anti-SRP, anti-topoisomerase I and anti-RNA polymerase III Abs. However, the results of anti-Mi-2, anti-U3 RNP, anti-Th/To, anti-hUBF and anti-Ku Abs remained discordant between the LB assay and IP assays at all cut-off levels. Detection of myositis- or SSc-related autoAbs using a commercial LB assay requires great caution since it can yield analytically false-positive or false-negative results. Key Points • A line blot (LB) assay is a multi-analyte platform capable of simultaneously detecting multiple antibodies with anti-nuclear specificities. • Detection of myositis- or systemic sclerosis-related autoantibodies using a commercial LB assay requires great caution since it can yield analytically false-positive or false-negative results.

Autoantibody profile in a cohort of Algerian patients with systemic sclerosis.

To describe the autoantibody profile in a cohort of Algerian patients with systemic sclerosis (SSc) and to determine clinical associations between SSc-related autoantibodies, disease subtypes and specific clinical features. Consecutive Algerian patients with SSc were included in the present study. In addition to clinical characterization, all subjects underwent autoantibody testing using indirect immunofluorescence, immunoenzymatic, and line immunoblot assays. A total of 150 patients were included in this study, 103 (68.7%) had limited cutaneous SSc (lcSSc), 42 (28%) had diffuse cutaneous SSc (dcSSc) and 5 (3.3%) had sine cutaneous scleroderma. One hundred thirty-five (90.0%) patients were positive for SSc-related autoantibodies, including 63 (42%) with more than one autoantibody. The two most frequent autoantibodies were anti-topoisomerase I (ATA) (76; 50.7%) and anti-SSA/Ro (49; 32.7%). Only 23 (15.3%) patients were positive for anticentromere; 9 (6%) were positive for anti RNA polymerase III; 5 (3.3%) for anti-U3 RNP; 3 (2%) for anti Th/To; 25 (16.7%) for anti-U1 RNP; 11 (7.3%) for anti-PM/Scl and 4 (2.7%) for anti-Ku. Anti-topoisomerase I was associated with dcSSc (p <0.0001), interstitial lung disease (ILD) (p <0.0001) and digital ulcers (p <0.0001). Anti-U3 RNP was associated with pulmonary arterial hypertension (PAH) (p=0.031). Notable similarities and differences in the prevalence of SSc-related autoantibodies were found in our population when compared to other ethnic groups. ATA and anti-U3 RNP may be a reliable biomarker for ILD and PAH. Further studies should be conducted to better understand the ethnic influence on disease expression and autoantibody production.

Using Autoantibodies and Cutaneous Subset to Develop Outcome-Based Disease Classification in Systemic Sclerosis.

To describe the associations between autoantibodies, clinical presentation, and outcomes among patients with systemic sclerosis (SSc) in order to develop a novel SSc classification scheme that would incorporate both antibodies and the cutaneous disease subset as criteria. Demographic and clinical characteristics, including cutaneous subset, time of disease and organ complication onset, and autoantibody specificities, were determined in a cohort of SSc subjects. Survival analysis was used to assess the effect of the autoantibodies on organ disease and death. The study included 1,325 subjects. Among the antibody/skin disease subsets, anticentromere antibody-positive patients with limited cutaneous SSc (lcSSc) (n = 374) had the highest 20-year survival (65.3%), lowest incidence of clinically significant pulmonary fibrosis (PF) (8.5%) and scleroderma renal crisis (SRC) (0.3%), and lowest incidence of cardiac SSc (4.9%), whereas the frequency of pulmonary hypertension (PH) was similar to the mean value in the SSc cohort overall. The anti-Scl-70+ groups of patients with lcSSc (n = 138) and patients with diffuse cutaneous SSc (dcSSc) (n = 149) had the highest incidence of clinically significant PF (86.1% and 84%, respectively, at 15 years). Anti-Scl-70+ patients with dcSSc had the lowest survival (32.4%) and the second highest incidence of cardiac SSc (12.9%) at 20 years. In contrast, in anti-Scl-70+ patients with lcSSc, other complications were rare, and these patients demonstrated the lowest incidence of PH (6.9%) and second highest survival (61.8%) at 20 years. Anti-RNA polymerase antibody-positive SSc patients (n = 147) had the highest incidence of SRC (28.1%) at 20 years. The anti-U3 RNP+ SSc group (n = 56) had the highest incidence of PH (33.8%) and cardiac SSc (13.2%) at 20 years. Among lcSSc patients with other autoantibodies (n = 295), the risk of SRC and cardiac SSc was low at 20 years (2.7% and 2.4%, respectively), while the frequencies of other outcomes were similar to the mean values in the full SSc cohort. Patients with dcSSc who were positive for other autoantibodies (n = 166) had a poor prognosis, demonstrating the second lowest survival (33.6%) and frequent organ complications. These findings highlight the importance of autoantibodies, cutaneous subset, and disease duration when assessing morbidity and mortality in patients with SSc. Our novel classification scheme may improve disease monitoring and benefit future clinical trial designs in SSc.

Clinical and laboratory characteristics of patients with systemic sclerosis positive for anti-ribonucleoprotein antibodies

Among the patients fulfilling the criteria for systemic sclerosis (SS), there is a subgroup without SS-specific antinuclear antibodies, but positive for anti-ribonucleoprotein (anti-U1 RNP) antibodies. The clinical significance of this type of antinuclear antibodies in SS is not clear. The presence of anti-U1 RNP antibodies is of great interest, since they are not only present in other rheumatic diseases, but are also considered as a marker for mixed connective tissue disease. Objective : to reveal the frequency of anti-U1RNP antibodies in patients with SS and to provide the clinical and laboratory characteristics of patients positive for these antibodies. Subjects and methods . 330 patients who fulfilled the 2013 ACR/EULAR criteria for SS and had been followed at the V.A. Nasonova Research Institute of Rheumatology from 2012 to 2017 were included. Anti-U1 RNP were determined by enzyme immunoassay (reference values: 0–25 U/ml). Results and discussion . Anti-U1RNP were detected in 65 (19.7%) patients with SS (85% of patients were highly positive; 15% were low-positive). The group included 8 men and 57 women; their mean age was 46±14 years. The disease duration was 11±7.9 years. Skin lesions were minimal; 59 (91%) patients had a limited form of the disease with swelling in the hands (scleredema) in 40% of cases and sclerodactyly in 60%. Raynaud's phenomenon was present in all the patients. One-half of the cases were observed to have peripheral ischemic disorders: digital scars and/or sores (43%), as well as necroses and ulcers of other sites, which were relatively rare (8%). Interstitial lung disease (ILD) was identified in 63% of cases. Elevated pulmonary artery systolic pressure (PASP) ≥40 mm Hg, as shown by echocardiography, was detected in 26% of cases and was associated mainly with the presence of ILD; pulmonary arterial hypertension was confirmed in three patients. Esophageal lesions were found in 61% of patients. One-third of patients had signs of scleroderma cardiopathy. The feature of the group was the common involvement of the locomotor system: joints with arthralgia and/or synovitis in 65% and muscles with mild and moderate myopathy in 43%. Erythrocyte sedimentation rate (ESR) and C-reactive protein levels were frequently elevated. The concurrence with Sjo gren's syndrome was common (in one-third of patients). None case of scleroderma renal disease was recorded; the mean values of kidney function were within the normal range; however, the glomerular filtration rate was lower than 80 ml/min/m2 in 17% of patients. All the patients were positive for antinuclear factor (HEp-2); in addition, there was rheumatoid factor (22%), antibodies against Ro/SS-A (41%), La/SS-B (18%), double-stranded DNA (42%), Scl70 (7%), and anticentromere antibodies (9%); 39 out of the 55 (71%) patients who were highly anti-U1 RNP-positive fulfilled the mixed connective tissue disease criteria proposed by R. Kasukawa et al. (1987). Conclusion . The investigation allows one to discuss of the presence of a special phenotype of SS, which is characterized by peculiar clinical manifestations in the presence of anti-U1 RNP overproduction.

Mixed Connective Tissue Disease Highlighting Diagnostic Exigency and Treatment Woes

Mixed connective tissue disease (MCTD) is a rare connective tissue disease characterized by manifestations that overlap symptoms typical of several other inflammatory diseases of connective tissue. A presence of anti-ribonucleoprotein antibodies (antiU1RNP) in high titer is a typical immunological finding. A 20 year old female complained of chilling and cyanosis of fingers on cold exposure since 5 years, with pain and numbness, hardening of skin of both hands, episodes of Raynaud’s phenomenon,gangrenous changes, self amputation of distal digit of middle finger. Systemic manifestations were also associated. A 15 year old female complained of thickening and tightening of skin of face and hands since 5 months, associated with joint pains, shortness of breath, dysphagia and photosensitivity of skin. Both cases were positive for Anti U1-RNP and Anti-SSA/Ro52 antibodies. Serology, radiology and histopathology were performed.. MCTD may be difficult to define as definite classification criteria are not fulfilled. Young and pediatric patients with skin manifestations must be investigated to initiate early treatment and monitor renal parameters. Patient compliance and trust in treating physician is a key to early diagnosis and treatment. Treating physician must recognize symptoms and refer patients to higher centres.

Antinuclear Antibody-Negative Systemic Lupus Erythematosus in an International Inception Cohort.

The spectrum of antinuclear antibodies (ANAs) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change is occurring in terminology to anticellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anticellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort. Anticellular antibodies were detected by IIF on HEp-2000 substrate using the baseline serum. Three serologic subsets were examined: ANA positive (presence of either nuclear or mixed nuclear/CMP staining), anticellular antibody negative (absence of any intracellular staining), and isolated CMP staining. The odds of being anticellular antibody negative versus ANA or isolated CMP positive was assessed by multivariable analysis. A total of 1,137 patients were included; 1,049 (92.3%) were ANA positive, 71 (6.2%) were anticellular antibody negative, and 17 (1.5%) had an isolated CMP. The isolated CMP-positive group did not differ from the ANA-positive or anticellular antibody-negative groups in clinical, demographic, or serologic features. Patients who were older (odds ratio [OR] 1.02 [95% confidence interval (95% CI) 1.00, 1.04]), of white race/ethnicity (OR 3.53 [95% CI 1.77, 7.03]), or receiving high-dose glucocorticoids at or prior to enrollment (OR 2.39 [95% CI 1.39, 4.12]) were more likely to be anticellular antibody negative. Patients on immunosuppressants (OR 0.35 [95% CI 0.19, 0.64]) or with anti-SSA/Ro 60 (OR 0.41 [95% CI 0.23, 0.74]) or anti-U1 RNP (OR 0.43 [95% CI 0.20, 0.93]) were less likely to be anticellular antibody negative. In newly diagnosed systemic lupus erythematosus, 6.2% of patients were anticellular antibody negative, and 1.5% had an isolated CMP. The prevalence of anticellular antibody-negative systemic lupus erythematosus will likely decrease as emerging nomenclature guidelines recommend that non-nuclear patterns should also be reported as a positive ANA.

Antinuclear Antibodies in Systemic Sclerosis: an Update.

Systemic sclerosis is an autoimmune disease characterized by fibrosis of skin and internal organs, vasculopathy, and dysregulation of immune system. A diagnostically important feature of immunological abnormalities in systemic sclerosis is the presence of circulating antinuclear antibodies, which may be detected in 90-95% of patients with either of the four main laboratory methods: immunofluorescence, enzyme-linked immunosorbent assay, immunodiffusion, and immunoblotting. There are several antinuclear antibodies specific for systemic sclerosis. These include antibodies against topoisomerase (anti-TOPO I), kinetochore proteins (ACA), RNA polymerase enzyme (anti-RNAP III), ribonuclear proteins (anti-U11/U12 RNP, anti-U1 RNP, anti-U3 RNP) and nucleolar antigens (anti-Th/To, anti-NOR 90, anti-Ku, antiRuvBL1/2, and anti-PM/Scl). Autoantibodies specific for systemic sclerosis have been linked to distinct clinical features. Therefore, detecting a particular antibody type is important in predicting a possible organ involvement and prognosis and may have an impact on monitoring and treatment.