U1-RNP Antibodies Research Articles

P166 Parotid benign lymphoepithelial cyst in connective tissue disease: a rare case series and literature review

Abstract Background/Aims Benign lymphoepithelial lesions are swellings of salivary glands caused by a reactive lymphoid infiltrate with follicular hyperplasia, obliterating the acinar glands and causing proliferation and disruption of the ductal epithelium. These have been described in HIV, lymphoma and Sjögren's syndrome. We report a case series with mixed connective tissue disease/Sjögren's syndrome and reviewed the literature with similar presentations in order to highlight this unusual manifestation. Methods Index patient: A 25-year-old lady presented with a history of arthralgia, fatigue and Raynaud's 3 years ago and was diagnosed by rheumatologist to have MCTD with ANA showing U1RNP, Ro positive and histones antibody positive. She was managed with mycophenolate and improved. A year ago she developed parotitis which improved with antibiotics. She recently came to the outpatient department with painful swelling in the parotid region. Blood counts remain normal, ESR 36 mm/hr , CRP 6 mg/dl, ACE level, HIV screening normal. MRI parotid showed bilateral multiple lymphoepitheial cysts in the parotid glands. Opinion was obtained from oncology and the ENT surgeon. No evidence of malignancy was found. In view of this, consensus opinion among rheumatologists was to stop mycophenolate and give 2gm rituximab. We also reviewed 10 cases of benign lymphoepithelial cyst arising in the parotid region in acquired immunodeficiency syndrome negative patients. Cases were from 8 published articles plus the three cases of benign lymphoepithelial cyst in a mixed connective tissue disease/Sjögren's syndrome in AIDS negative patients reported in Table 1. Most of the patients had been treated surgically, however, immune therapy is sufficient. Results: Conclusion Benign lymphoepitheial cysts have been described in patients with sarcoidosis, HIV, cancer and CTD. Our patients had features of MCTD with Sjögren's syndrome and manifested with benign lymphoepithelial cysts in the parotids, which is very unusual. Parotid swelling in connective tissue disease requires evaluation and multidisciplinary input. Benign lymphoepithelial cysts will not require any surgery; once malignancy is excluded, they will require modification of immune therapy. Disclosure N. Palaniappan: None. S. Nallasivan: None.

A REFRACTORY CASE OF HYPOCOMPLEMENTEMIC URTICARIAL VASCULITIS

<h3>Introduction</h3> Hypocomplementemic Urticarial Vasculitis (HUV) is a rare small vessel vasculitis. Patients present to allergy clinic with recurrent urticarial lesions. Proposed diagnostic criteria include 2 major criteria: recurrent urticarial lesions and hypocomplementemia, with at least 2 minor criteria: dermal biopsy showing leukocytoclastic vasculitis, arthralgias/arthritis, organ involvement, or elevated anti-C1q antibodies. We describe here the clinical presentation and therapeutic management of a refractory case of HUV. <h3>Case Description</h3> A 28-year-old female presented with a 2-year history of inflammatory arthritis and recurrent hives. Workup revealed hypocomplementemia: C3: 60, C4:10, decreased serum C1q<3.6, elevated anti-C1q antibody (102) and negative autoimmune markers. Cutaneous biopsy showed IgG/C3 at the basement membrane. She had been diagnosed with HUV and treated without benefit with different medications regimens including prednisone, hydroxychloroquine, colchicine, and dapsone all discontinued due to adverse effects/ineffectiveness. Patient was then tried on Methotrexate and Cyclosporine with limited benefit and later on Mycophenolate and omalizumab with minimal improvement. Over time, she developed pulmonary capillaritis, pericarditis, and episcleritis. She progressively developed a multi-organ, complex syndrome all of which was attributed to HUVS. After multiple failed therapies and poor control of urticaria multi-disciplinary decision was made to start Rituximab. <h3>Discussion</h3> Suspicion of HUVS should increase when hives do not respond to therapy, last>24 hours, and leave hyperpigmentation upon resolution. Differential diagnosis includes Muckle-Wells syndrome (hearing loss), Cogan syndrome (progressive hearing/vision loss), Sharp syndrome (positive U1-RNP antibodies), and SLE (positive ANA, normal levels of C1 esterase inhibitor). The case describes an aggressive form of HUV and highlights refractory disease with escalating therapies.

A RARE CASE REPORT OF MULTIPLE CONNECTIVE TISSUE DISEASE WITH SEVERE PULMONARY HYPERTENSION

A 38 year old female presented with complaints of tightness, dryness, hyperpigmentation of skin , tightness of mouth, tingling numbness and pain in ngers while handling cold water since 6 months. Exertional breathelessness since 1 month .She had history of swelling of hands six months back. Finger examination showed sclerodactyly and ulceration over skin on interphalangeal joints of both hands without any deformity .Since clinical ndings were suggestive of Raynaud's phenomenon, sclerodactyly, swelling of hands , scleroderma, she was further investigated for presence of connective tissue disease . On immunological investigations , ANA prole was positive with presence of strong positive U1RNP antibodies (titre&gt;1:1600). Chest x ray and 2d echocardiography revealed presence of Pulmonary Hypertension. She was diagnosed with Multiple Connective Tissue Disease (MCTD) with severe pulmonary hypertension based on clinical , radiological and laboratory ndings satisfying Alarcon Segovia criteria.

Relationship between changes observed in nailfold capillaroscopy and serological profile, lung fibrosis, and elevated risk of pulmonary hypertension in patients with systemic sclerosis and mixed connective tissue disease

Microvascular changes play a significant role in systemic sclerosis (SSc) and mixed connective tissue disease (MCTD). The most serious complications of SSc and MCTD are lung fibrosis (LF) and pulmonary hypertension (PH). To determine the relationship of the changes observed in capillaries with the serological profile, LF, PH, and finger ulcerations in patients with SSc and MCTD. The tested group comprised 80 persons (61 SSc, 19 MCTD); mean age 53.6 ±13.6 years. Patients were qualified to the LF group based on HRCT. Likelihood of PH was determined using echocardiography. The presence of antinuclear antibodies (ANA) was assessed using indirect immunofluorescence, while ANA profile, and sclerosis profile were assessed using EUROIMMUN kits, and antiphospholipid antibodies (aPL) using the ELISA method. Capillaroscopy was performed using the Nikon CPS 160 optical microscope. The following were found: a relationship between occurrence of anti-SS-A (p = 0.006) and anti-centromere B antibodies (p = 0.012) and ramified vessels, between anti-SS-B and capillary haemorrhages (p = 0.019), a positive correlation between NOR90 antibodies and winding loops (p = 0.021), PM-Scl 100 antibodies and enlarged vessels (p = 0.033), a negative correlation between Scl-70 antibodies and winding loops (p = 0.033), and a relationship between aCL and winding loops (p = 0.002). No relationship between the capillaroscopy image and PH risk was found. A positive correlation was found between avascularisation areas and LF and between giant capillaries and finger ulcerations. A negative correlation was found between U1-RNP antibodies and finger ulcerations (p = 0.009), and a positive correlation between antibodies to fibrillarin and ulcerations (p = 0.028). SS-A, SS-B and anti-centromere antibodies are associated with the late phase of sclerodermic microangiopathy. Avascularisation areas significantly correlate with a higher prevalence of LF. U1-RNP antibodies have a protective role, while anti-fibrillarin antibodies are the risk factor for finger ulcerations.

Association study between immune-related miRNAs and mixed connective tissue disease

BackgroundMixed connective tissue disease (MCTD) is a rare condition that is distinguished by the presence of specific U1-RNP antibodies. Information about its etiopathology and diagnostics is still unclear. miRNAs such as miR-146, miR-155, and miR-143 emerged as key regulators of the immune system, known to be involved in the development of autoimmune diseases and cancers. We performed an association study between immune-related miRNAs and MCTD severity and susceptibility.MethodsA total of 169 MCTD patients and 575 healthy subjects were recruited to the case–control study. The miRNA polymorphisms were genotyped using TaqMan SNP genotyping assay. TNF-α, IL-6, and IFN-γ levels in serum were determined using ELISA. qRT-PCR of TRAF6, IRAK1, and microRNAs was performed using Taqman miRNA assays and TaqMan Gene Expression Assays.ResultsmiR-146a rs2910164 G allele and GG genotype as well as miR-143 rs713147 A allele were more frequent in healthy subjects than in MCTD patients. miR-146a rs2910164 CC genotype and miR-143 T-rs353299*T-rs353291*T-rs713147*G-rs353298 and C-rs353299*C-rs353291*T-rs713147*A-rs353298 haplotypes were associated with MCTD susceptibility. miR-146a rs2910164 C/T was associated with scleroderma and lymphadenopathy. miR-143 rs353299 C/T was associated with swollen fingers or hands, the presence of enlarged lymph nodes, and pericarditis/pleuritis. miR-143 rs353298 A/G was associated with the occurrence of pericarditis/pleuritis and scleroderma. miR-143 rs353291 T/C showed association with pericarditis/pleuritis. The serum TNF-α, IFN-γ, and IL-6 levels were significantly higher in MCTD patients compared to healthy subjects. miR-143 SNPs were associated with higher proinflammatory cytokine concentration in serum only in healthy controls. IRAK1 and TRAF6 expression were higher in the MCTD patients compared to controls.ConclusionsThe results of our case–control study indicate the possible significance of miR-146a and miR-143/145 in the susceptibility and clinical picture of MCTD.

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 anti-NR2 and U1RNP antibodies with neurotoxic inflammatory mediators in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus

Autoantibodies (auto Abs) and inflammatory mediators (IMs) in cerebrospinal fluid (CSF) may be involved in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). It is suggested that anti-N-methyl D-aspartate receptor NR2 subunit (NR2) Ab can develop NP manifestation after blood-brain barrier (BBB) abruption. We also reported the association between NPSLE and CSF anti-U1RNP Ab. In the present study, combined effects of CSF anti-NR2 and anti-U1RNP Abs on IMs in patients with NPSLE were examined. CSF samples were collected from 69 patients with NPSLE and 13 non-NPSLE controls. CSF anti-NR2 and anti-U1RNP Abs were determined using ELISA. Levels of IL-6, IL-8, and monokine induced by IFN-γ (MIG) in CSF were measured by quantitative multiplex cytokine analysis. CSF IL-6 levels were higher in CSF anti-NR2-positive than in CSF anti-NR2-negative patients (p = 0.003) and non-NPSLE controls (p = 0.015) and were positively correlated with anti-NR2 titer (r = 0.42). CSF IL-8 levels were higher in CSF anti-U1RNP-positive than in CSF anti-U1RNP-negative patients (p = 0.041). CSF MIG levels were more elevated in CSF anti-NR2-positive (p = 0.043) and anti-U1RNP-positive patients (p = 0.029) than in non-NPSLE controls. Additionally, in double positive (DP; both anti-NR2 and U1RNP Ab positive) group, CSF IL-6 and MIG levels were significantly higher than in the double negative (DN; both anti-NR2 and U1RNP Ab negative) group. However, combined effect of both Abs on IM elevation and clinical manifestation was not clear. CSF anti-NR2 and anti-U1RNP Abs have different effects on the elevation of CSF IM levels in patients with NPSLE. Additional effect of anti-U1RNP Abs on anti-NR2 Ab-mediated NP manifestation, however, was not recognized in our study.

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.

Reduced diffusing capacity for carbon monoxide predicts borderline pulmonary arterial pressure in patients with systemic sclerosis.

Early intervention in pulmonary arterial hypertension associated with systemic sclerosis (SSc) may improve its prognosis. We aimed to establish an algorithm to detect mean pulmonary artery pressure (mPAP) > 20mmHg using non-invasive examinations in SSc patients by modifying the DETECT algorithm. This study included SSc patients who underwent right heart catheterization (RHC) in our hospital during 2010-2018. Following variables were assessed for performance to predict mPAP ≥ 25mmHg or > 20mmHg; anti-centromere or U1-RNP antibody, plasma BNP level, serum urate level, right axis deviation, forced vital capacity (FVC)/diffusing capacity for carbon monoxide (DLCO) ratio, and tricuspid regurgitation velocity. Of 58 patients enrolled in this study, 24 had mPAP of ≥ 25mmHg and 9 had mPAP of 21-24mmHg. Among variables tested, only FVC/DLCO elevated similarly in patients with mPAP of ≥ 25mmHg (median 2.5) and those with mPAP of 21-24mmHg (median 2.5) compared to those with mPAP of ≤ 20mmHg (median 1.5). Given the particularly good correlation between DLCO and mPAP of > 20mmHg, each variable was weighted according to its odds ratio and the total weighted score was calculated. The total weighted score exhibited a good predictive performance for mPAP of > 20mmHg with its sensitivity of 87.5% and specificity of 92%. Among conventional risk factors for PAH, decreased DLCO may predict mPAP > 20mmHg with priority in SSc patients. Weighting DLCO may improve the performance of screening algorithm for early SSc-PAH.

Characteristics and Survival of Anti-U1 RNP Antibody-Positive Patients With Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue diseases (CTDs). This study aimed to investigate the clinical and hemodynamic characteristics and survival of anti-U1 RNP-positive patients with CTD-associated PAH, with a focus on systemic sclerosis (SSc)-associated PAH. We implemented a prospective database that included patients with CTD-associated PAH for whom there were clinical, autoantibody, and mortality data. We compared clinical and hemodynamic characteristics to anti-U1 RNP antibody status. We then assessed whether anti-U1 RNP antibodies could be a prognostic factor in CTD-associated PAH with a focus on SSc-associated PAH. We studied a total of 342 patients with CTD-associated PAH, of whom 36 (11%) were anti-U1 RNP antibody positive. Anti-U1 RNP-positive patients were younger and less functionally impaired than were anti-U1 RNP-negative patients in CTD- and SSc-associated PAH. Hemodynamic parameters were similar in anti-U1 RNP-positive and anti-U1 RNP-negative patients. In CTD-associated PAH, anti-U1 RNP positivity was associated with decreased mortality in univariable analysis (hazard ratio 0.34 [95% confidence interval 0.18-0.65], P < 0.001). In multivariable analysis, anti-U1 RNP positivity was also associated with decreased mortality (hazard ratio 0.44 [95% confidence interval 0.20-0.97], P = 0.043) independently of age, sex, functional parameters, lung involvement, and hemodynamic parameters. Results were similar in SSc-associated PAH, although the association between anti-U1 RNP positivity and survival did not reach significance in univariable (hazard ratio 0.47 [95% confidence interval 0.22-1.02], P = 0.055) and multivariable (hazard ratio 0.47 [95% confidence interval 0.20-1.11], P = 0.085) analyses. Anti-U1 RNP positivity was associated with distinct clinical characteristics and survival in CTD- and SSc-associated PAH. While hemodynamic parameters were similar in anti-U1 RNP-positive and anti-U1 RNP-negative patients, our results suggest that anti-U1 RNP positivity could be a factor protecting against mortality in CTD- and SSc-associated PAH.

70.: Vitamin R therapy in scleromyositis: A novel approach for a rare disorder

L.W. is a 48-year-old right handed female with a scleroderma overlap syndrome (scleromyositis) manifested by systemic sclerosis (skin and gastrointestinal involvement) with a predominantly proximal necrotizing myositis. It is likely that this is a rare polymyositis/scleroderma overlap or anti-synthetase syndrome. She is persistently antibody negative for U1RNP, PmScl, Ro, La, Jo-1 and Ku antibodies. Antibodies to smooth muscle and skeletal muscle are also negative. Her symptoms were treatment resistant to immunosuppression until B cell depletion with rituximab. We discuss her course and prognosis. The patient presented in 2008 with progressive gastrointestinal symptoms with malabsorption, eventually requiring total parenteral nutrition. Total parenteral nutrition resulted in improved general condition with weight gain. She was being treated with combination of methotrexate and prednisolone when she developed insidiously progressive proximal weakness, with parallel progression of skin thickening. Peak creatine kinase (CK) was recorded at 1800 u/L. There was no improvement in muscle strength with steroid reduction. Electromyogram in 2010 suggested a proximal predominant necrotizing myositis. We postulate she has a scleroderma overlap syndrome. She was treated with rituximab in January 2012. L.W. was monitored clinically with CK levels. B cell depletion was confirmed with CD20 count of

THU0058 Intestinal Microbiota Plays A Critical Role in the Production of Antinuclear Antibodies in Lymphopenia-Induced Autoimmunity

BackgroundProduction of antinuclear autoantibodies (ANAs) is one of the major characteristics of the systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), but the mechanisms of their production are not...

AB0805 Nailfold capillaroscopy findings are different between patients with U1RNP antibody and systemic sclerosis or patients with systemic lupus erythematosus and U1RNP antibody

BackgroundNailfold capillaroscopy (NC) is the best tool to study microcirculation in patients with Raynaud’s phenomenon (RF) or patients with connective tissue diseases. There are some characteristic capillaroscopy findings in systemic...

AB0416 Clinical and immunological association with autoantibodies to cellular antigen in a cohort of 532 sle patients from a single center.

Backgroundautoantibodies (autoabs) to cellular antigens can be associated with specific clinical and immunological subsets of Systemic Lupus Erythematosus (SLE).Objectivesto analize the frequencies of different autoabs detected by counterimmunoelectrophoresis (CIE) and...

Systemic sclerosis: demographic, clinical and serological features in 100 Iranian patients

To evaluate demographic, clinical and laboratory features associated with scleroderma-specific auto-antibodies. Sera of 100 patients with systemic sclerosis (SSc) were analyzed by an indirect immunofluorescence technique with HEp-2 cells as a substrate. Specific ANA such as anti-centromere antibodies (ACA), anti-topoisomerase (TOPO), anti-RNA polymerase III (Pol 3), anti-U3-RNP (U3-RNP), anti-Th/To (Th/To) and anti-PM/Scl (PM/Scl) were detected by line immunoassay and anti-U1-RNP (U1-RNP) by ELISA. Frequency of clinical features associated with a specific antibody group was reported cumulatively over the follow-up period. Frequency of specific clinical features was compared across the two disease subtype including limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) as well as the auto-antibody groups. Ninety-four percent of patients were ANA positive with significant higher skin score, Raynauds and digital ulcer/gangrene. Anti-TOPO was detected in 71% of all patients, in 90.5% of dcSSC and in 65.8% of lcSSc. Anti-TOPO was significantly associated with dcSSc, higher skin score, digital ulcer/gangrene, pulmonary fibrosis, DLCO <70%. U1-RNP antibody was associated with lower fibrosis in lung. ACA was positive in 7% of patients and exclusively in those with lcSSc. We did not find association between gender and presence of auto-antibodies. Anti-TOPO antibody had a high prevalence in contrast to low prevalence of ACA antibody. There were no differences in clinical subtypes of the disease in patients with positive anti-TOPO and positive ACA. Differences in prevalence of auto-antibodies are suggestive of further genetic study.

English

INTRODUCTION: Mixed connective tissue disorder, unlike other connective tissue disorders have a milder course. MTCD with only necrotizing cutaneous vasculitis without organ damage respond well to Immunosuppresents and Steroids. CASE REPORT: Middle aged Young lady presented with multiple non healing large pressure sores and multiple nonblanchable purpuric lesions. She was bedridden, anaemic and with significant weight loss. All her major organ functions were normal. Her U1 RNP Antibody is positive and Skin Biopsy showed positive direct fluorescent test for IgG. She responded well to immunosuppresants and steroids. CONCLUSION: This patient who presented with MTCD, with predominant necrotizing cutaneous vasculitis and without major organ involvement showed good recovery and responded well to cyclophosphamide pulse therapy, daily azathioprine and good wound care.

Clinical significance of U1-nuclear ribonucleoprotein antibodies in Chinese patients with systemic sclerosis

Objective To investigate clinical relevance of U1-nuclear ribonucleoprotein antibody (anti-U1 RNP) in Chinese patients with systemic sclerosis (SSc). Methods In total, 131 Chinese patients with SSc were prospectively and consecutively recruited into Scleroderma Trials and Research Group sponsored by European League Against Rheumatism (EUSTAR) from clinical database of Peking Union Medical College Hospital ( PUMCH). Their clinical features, visceral lesions and laboratory findings including detection of anti- U1 RNP were recorded. Relevance between existing anti-U1 RNP and clinical characteristics and other laboratory indicators of SSc was analyzed statistically. Results Eighty-seven of the 131 patients presented as diffused SSc (dSSc) , 36 limited SSc ( lSSc) and eight SSc/systemic lupus erythematosus (SLE) overlap syndrome, with positive rate of anti-U, RNP of 28. 2 (37/131) percent in patients with SSc. Positive rate of anti-U1 RNP in dSSc was similar to that in lSSc groups [28. 7% (25/87) and 25. 0% ( 9/36 ) , respectively, P = 0. 673]. But significantly higher prevalence of pulmonary arterial hypertension and cardiac involvement, and less white blood cell and platelets counts were observed in the patients with positive anti-U1 RNP than in those with negative anti-U1 RNP (all P 0. 05 ) . Detection rate of anti-DNA topoisomerase I ( Scl-70 antibody) was higher in SSc patients with negative anti-U, RNP. Conclusions U1 RNP antibody is a common antibody in Chinese patients with SSc, and detection for it combined with other autoantibodies will be helpful for diagnosing of SSc and predicting development of pulmonary arterial hypertension, cardiac and hematological involvements in them. Key words: Scleroderma, systemic; Autoantibodies; Diagnosis

Anti–U1 RNP antibodies in cerebrospinal fluid are associated with central neuropsychiatric manifestations in systemic lupus erythematosus and mixed connective tissue disease

To determine the significance of anti-U1 RNP antibodies in the cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD) who have central neuropsychiatric SLE (NPSLE). The frequency of antinuclear antibodies including anti-U1 RNP antibodies in the sera and CSF of 24 patients with SLE and 4 patients with MCTD, all of whom had neuropsychiatric syndromes, was determined using an RNA immunoprecipitation assay and an enzyme-linked immunosorbent assay. The frequency of anti-U1 RNP antibodies in the CSF of patients with central NPSLE was examined, and the anti-U1 RNP index ([CSF anti-U1 RNP antibodies/serum anti-U1 RNP antibodies]/[CSF IgG/serum IgG]) was compared with CSF interleukin-6 (IL-6) levels and the albumin quotient (Qalb, an indicator of blood-brain barrier damage). CSF and serum antibodies against U1-70K, U1-A, and U1-C, including autoantigenic regions, were examined, and the U1-70K, U1-A, and U1-C indices as well as the anti-U1 RNP index were calculated. CSF anti-U1 RNP antibodies with an increased anti-U1 RNP index showed 64.3% sensitivity and 92.9% specificity for central NPSLE. The anti-U1 RNP index did not correlate with CSF IL-6 levels or the Qalb. The anti-U1-70K index was higher than the anti-U1-A and anti-U1-C indices in the CSF of anti-U1 RNP antibody-positive patients with central NPSLE. The major autoantigenic region for CSF anti-U1-70K antibodies appeared to be localized in U1-70K amino acid 141-164 residue within the RNA-binding domain. The frequency of anti-U1 RNP antibodies in the CSF and the anti-U1 RNP index are useful indicators of central NPSLE in anti-U1 RNP antibody-positive patients. The predominance of anti-U1-70K antibodies in CSF suggests intrathecal anti-U1 RNP antibody production.

Periorbital Cutaneous Neonatal Lupus

The authors report 3 infant girls with a similar periorbital eruption. A 5-month-old infant girl presented with a 3-month history of a photosensitive facial eruption that had failed to respond to topical 1% hydrocortisone cream. The otherwise healthy infant was the product of a term pregnancy. The 25-year-old mother was in good health except for occasional arthralgias. She had 2 other healthy children. Physical examination revealed a well-developed, well-nourished infant with annular, polycyclic, erythematous scaly plaques involving the cheeks and periorbital region (Figure 1). Potassium hydroxide scraping from the face was negative for dermatophyte and yeast. Laboratory studies revealed normal complete blood cell count, normal liver function tests, strongly positive anti-SSA antibody at 118 units (>80 units, strongly positive), and a negative anti-SSB antibody. Cardiac examination and electrocardiogram (ECG) were also normal. Laboratory evaluation of the mother revealed a positive anti-SSA at 158 units and mild anemia, but anti-SSB, anti-Smith, U1RNP, and anti-Scl-70 antibodies were all negative. Within 4 months the facial eruption cleared completely with the use of desonide cream 0.05% applied twice a day and sun protection. A 6-month-old girl was referred for dermatitis that began on the trunk and face at about 2 months of age. Although the truncal component resolved after 2 months, the facial dermatitis persisted. The infant was in good health and was the first-born child. The mother was known to have Sjögren syndrome. Physical examination revealed the characteristic erythematous, annular, scaling, polycyclic plaques along the forehead, periorbital cheeks, and eyelids (Figure 2). Laboratory evaluation of the infant revealed normal complete blood cell count, liver function tests, and chemistry profile. Anti-SSA antibody was positive at >6 units (reference, <1 unit) and anti-SSB antibody was positive at 2.84 units (reference, <1 unit). U1RNP antibody was negative. Cardiac examination and ECG were normal. The skin abnormalities cleared completely in 6 weeks with the topical application of tacrolimus 0.03% ointment and sun protection. A 5-month-old girl presented with a 2-month history of a persistent facial dermatitis. The infant was in good health and was the product of a healthy first pregnancy and delivery. The mother was in good health. Physical examination of the infant revealed erythematous, annular, polycyclic periorbital patches (Figure 3). Laboratory evaluation revealed positive SSA and SSB antibodies (units unavailable) and normal complete blood cell count, liver function tests, and chemistry profile. Cardiac examination and ECG were normal. The mother's laboratory results were also positive for anti-SSA and anti-SSB antibodies (units unavailable). The infant's facial eruption resolved without specific treatment.

Detection of anti-SSA antibodies by indirect immunofluorescence.

HEp-2 cells that overexpress the human 60-kDa SSA antigen have been used to improve sensitivity and specificity for the detection of anti-SSA antibodies by indirect immunofluorescence. We describe a survey on the detection of anti-SSA antibodies using a commercial substrate that overexpresses SSA. The evaluation was done on 18 371 consecutive samples submitted to the laboratory for detection of anti-nuclear antibodies, from which 188 anti-SSA antibody-containing and clinically documented samples were obtained. The presence of anti-SSA antibodies produced a distinct bright speckled pattern with nucleolar staining in 10-20% of interphase cells. The identity of all anti-SSA antibodies was confirmed by dot-blot analysis. Samples containing anti-SSA antibodies were separated into three main groups: group I, distinctive SSA pattern and other nuclear staining (50%); group II, only the distinctive SSA pattern (29%); group III, nuclear staining but without the distinctive SSA pattern (21%). Anti-SSA antibodies with concurrent SSB antibodies were associated with group I, whereas anti-SSA antibodies with concurrent U(1)-RNP antibodies were associated with group III. Group I included mainly patients with Sjogren syndrome and systemic lupus erythematosus (SLE), whereas group III included patients with mixed connective tissue disease and SLE. Diseases not classically associated with the presence of anti-SSA antibodies were found in group II in >50% of the cases. SSA-positive individuals were identified in a population selected on the basis of HEp-2000 positivity. Our study highlights diseases associated with anti-SSA antibodies and associations between the presence of the distinctive SSA pattern on HEp-2000 and some clinical conditions.