Diagnostic accuracy of the FIDIS multiplex fluorescent microsphere immunodetection system for anti-extractable nuclear antigen (ENA) antibodies in connective tissue diseases

2007 ◽  
Vol 45 (4) ◽  
Author(s):  
Martine Vercammen ◽  
Patricia Meirlaen ◽  
Jacques Sennesael ◽  
Brigitte Velkeniers ◽  
Sara T'Kint ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Diagnostic Accuracy ◽  
Connective Tissue Diseases ◽  
Nuclear Antigen ◽  
Fluorescent Microsphere ◽  
Extractable Nuclear Antigen

AbstractClin Chem Lab Med 2007;45:505–12.

scholarly journals Antifibrillarin autoantibodies present in systemic sclerosis and other connective tissue diseases interact with similar epitopes.

1995 ◽  
Vol 181 (3) ◽  
pp. 1027-1036 ◽  
Author(s):  
K N Kasturi ◽  
A Hatakeyama ◽  
H Spiera ◽  
C A Bona
Keyword(s):  
Systemic Sclerosis ◽  
Connective Tissue ◽  
Lupus Erythematosus ◽  
Competitive Inhibition ◽  
Molecular Mimicry ◽  
Connective Tissue Diseases ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Recombinant Fusion Proteins ◽  
Epstein Barr

Autoantibodies specific against fibrillarin, a 34-kD nucleolar protein associated with U3-snRNP, are present in patients with systemic sclerosis (SSc). To understand the mechanisms involved in the induction of these autoantibodies, we prepared a series of human fibrillarin recombinant proteins covering the entire molecule and analyzed their interaction with the autoantibodies present in various connective tissue diseases. Our results showed that antifibrillarin autoantibodies are present not only in SSc, as previously reported, but also in a variety of other connective tissue diseases. Patients with SSc (58%), mixed connective tissue diseases (60%), CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dismotility, sclerodactyly, and telangiectasia syndrome) (58%), systemic lupus erythematosus (39%), rheumatoid arthritis (60%), and Sjogern's syndrome (84%) showed presence of antifibrillarin autoantibodies. Results obtained from competitive inhibition radioimmunoassay and Western blot analyses with purified recombinant fusion proteins revealed that these autoantibodies react primarily with epitope(s) present in the NH2- (AA 1-80) and COOH-terminal (AA 276-321) domains of fibrillarin. Autoantibodies reacting with internal regions of fibrillarin are less frequent. Analysis of the hydrophilicity profiles of reactive peptides showed presence of three potential antigenic sites in the NH2- and two in the COOH-terminal regions. While a hexapeptide sequence NH2 terminus of fibrillarin is shared with an Epstein-Barr virus-encoded nuclear antigen, the COOH-terminal region shares sequence homology with P40, the capsid protein encoded by herpes virus type 1. Interestingly, these two regions of fibrillarin also contain the most immunodominant sequences, as predicted by surface probability and the Jameson and Wolf antigenic index. These observations suggest that molecular mimicry might play an important role in the induction of antifibrillarin autoantibodies.

scholarly journals Association of Immunofluorescence pattern of Antinuclear Antibody with Specific Autoantibodies in the Bangladeshi Population

2015 ◽  
Vol 40 (2) ◽  
pp. 74-78 ◽  
Author(s):  
S Sharmin ◽  
S Ahmed ◽  
A Abu Saleh ◽  
F Rahman ◽  
MR Choudhury ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Lupus Erythematosus ◽  
Antinuclear Antibody ◽  
Research Work ◽  
Connective Tissue Disorder ◽  
Nuclear Antigen ◽  
Dot Blot ◽  
Serum Samples ◽  
Speckled Pattern ◽  
Extractable Nuclear Antigen

Antinuclear antibody (ANA) is useful in the diagnosis of connective tissue disorder (CTD). Association of specific autoantibodies with the immunofluorescence pattern of ANA in CTD, noted in western literature has been considered as reference in all over the world. However, in Bangladesh no such research work or data correlating the autoantibodies and their ANA patterns is found. Objective of the study was to identify an association between immunofluorescence patterns of antinuclear antibody on HEp-2 cell and more specific antinuclear reactivities (e.g. anti-dsDNA and anti-extractable nuclear antigen) in the serum samples of CTD patients. Serum samples of 152 CTD patients (Systemic lupus erythematosus, Rhumatoid arthritis, Sjogren´s syndrome, Systemic sclerosis, Polymyositis, Mixed connective tissue disease) were diagnosed clinically, attending at Bangabandhu Sheikh Mujib Medical University (BSMMU) during the study period of January, 2010 to December, 2010. Samples were subjected for ANA testing by Indirect Immunofluorescence (IIF) on HEp-2 cell (ALPHADIA) in dilution of 1:40, anti-dsDNA by ELISA and anti- extractable nuclear antigen (anti-ENA) by Dot Immunoblot. Dot blot strips were tested for anti-Sm, anti-RNP, anti-SSA/Ro, anti-SSB/La, anti-Scl-70 and anti-Jo-1. Out of 152 patients 110 (72.3%) cases were ANA positive by IIF on HEp-2 cell. ANA positive sera exhibited four fluorescence patterns such as speckled (50.8%), peripheral (21.6%) ,homogenous (18.1%) and nucleolar pattern (9%). Peripheral pattern and homogenous pattern was predominantly associated with anti-dsDNA (p<0.05). Speckled pattern was significantly associated with anti-ENA (p<0.05).The most commonly identified antinuclear autoreactivity was directed towards anti-RNP (25.7%) then anti-Scl-70 (20%), anti-SSA (14.2%) and anti-SSB (5.7%). Multiple anti-ENA reactivities were identified in 34.28% cases. Peripheral and homogenous pattern is strongly associated with anti-dsDNA and speckled pattern may predict anti-ENA (specially ribonucleoprotiens). As a definite correlation between the ANA patterns and the group of antibodies was detected by dot immunoblot, one could predict presence of certain specific auto antibodies for a particular ANA pattern identified. This may restrict on the cost of laboratory investigations in a developing country like Bangladesh. Thus, ANA-IIF method may reduce the expense of detailed immunological work-up with minimal loss in diagnostic accuracy.Bangladesh Med Res Counc Bull 2014; 40 (2): 74-78

Mixed Connective Tissue Disease in Childhood

1986 ◽  
Vol 7 (10) ◽  
pp. 309-314
Author(s):  
Bernhard H. Singsen
Keyword(s):  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Rheumatic Diseases ◽  
Mixed Connective Tissue Disease ◽  
Overlap Syndrome ◽  
Point Of View ◽  
Nuclear Antigen ◽  
Extractable Nuclear Antigen ◽  
First Child ◽  
One Year

Rheumatic diseases with overlapping clinical features have been known since at least 1900 under such descriptive designations as "sclerodermatomyositis," "lupoderma," "rupus," and others. These hybrid descriptors recognize the occasional mixing of features of the classic rheumatic disorders, rheumatoid arthritis, scleroderma, dermatomyositis, and systemic lupus erythematous (SLE), in the same patient. However, because of the absence of precise pathogenetic and etiologic information, even the traditional rheumatic diseases have been largely classified on the basis of aggregations of clinical, histologic, and immunologic findings. In 1972, Sharp and colleagues first described 26 adults with a new syndrome, which they defined as mixed connective tissue disease (MCTD). A major contribution of Sharp and his colleagues was to name and attempt to classify an overlap syndrome in explicit clinical terms and to associate it with specific autoantibodies directed against "extractable nuclear antigen" (ENA). One year later, the first child with MCTD was reported, and in 1977 a series of 14 children with MCTD was first investigated. Where does mixed connective tissue disease, in both children and adults, stand now after more than a decade of study? Directly, the concept of MCTD has focused our attention upon the description of overlapping features of the rheumatic diseases, and it has forced us to confront whether "lumping" or "splitting" descriptors serves the patient from a therapeutic or prognostic point of view.

scholarly journals Evaluation of an Automated Screening Assay, Compared to Indirect Immunofluorescence, an Extractable Nuclear Antigen Assay, and a Line Immunoassay in a Large Cohort of Asian Patients with Antinuclear Antibody-Associated Rheumatoid Diseases: A Multicenter Retrospective Study

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Seri Jeong ◽  
Hyunyong Hwang ◽  
Juhye Roh ◽  
Jung Eun Shim ◽  
Jinmi Kim ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Indirect Immunofluorescence ◽  
Lupus Erythematosus ◽  
Antinuclear Antibody ◽  
Nuclear Antigen ◽  
University Hospitals ◽  
Screening Assay ◽  
Extractable Nuclear Antigen ◽  
Automated Screening

We assessed the diagnostic utility of the connective tissue disease (CTD) screen as an automated screening test, in comparison with the indirect immunofluorescence (IIF), EliA extractable nuclear antigen (ENA), and line immunoassay (LIA) for patients with antinuclear antibody- (ANA-) associated rheumatoid disease (AARD). A total of 1115 serum samples from two university hospitals were assayed using these four autoantibody-based methods. The AARD group consisted of patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren’s syndrome (SS), and mixed connective tissue disease (MCTD). The qualitative results of all four autoantibody assays showed a significant association with AARDs, compared to controls (P<0.0001 for all). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for differentiating total AARDs, SLE, SSc, SS, and MCTD from controls were 0.89, 0.93, 0.73, 0.93, and 0.95, respectively. The ROC-AUCs of combination testing with LIA were slightly higher in patients with AARDs (0.92) than those of CTD screen alone. Multivariate analysis indicated that all four autoantibody assays could independently predict AARDs. CTD screening alone and in combination with IIF, EliA ENA, and LIA are potentially valuable diagnostic approaches for predicting AARDs. Combining CTD screen with LIA might be effective for AARD patients.

scholarly journals POS0862 NAILFOLD CAPILLAROSCOPY IN UNDIFFERENTIATED AND MIXED CONNECTIVE TISSUE DISEASES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 686-686
Author(s):  
C. Pizzorni ◽  
G. Ferrari ◽  
C. Schenone ◽  
E. Gotelli ◽  
S. Paolino ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Raynaud’S Phenomenon ◽  
Connective Tissue Diseases ◽  
Serum Levels ◽  
Capillary Density ◽  
Absolute Number ◽  
Raynaud's Phenomenon ◽  
Statistical Correlation ◽  
Nuclear Antigen ◽  
Microvascular Damage

Background:Microvascular damage is a frequent feature in connective tissue diseases (CTDs) and can be easily detected trough nailfold videocapillaroscopy (NVC) (1,2). Mixed and Undifferentiated connective tissue diseases (MCTD and UCTD) do not show a specific and unique NVC pattern (3). However, a variety of microvascular abnormalities can occur in these two CTDs, both non-specific or specific for the scleroderma like-pattern (3-5).Objectives:To retrospectively assess and compare nailfold microangiopathy observed by NVC in MCTD and stable UCTD versus primary Raynaud’s phenomenon (PRP) (6). In addition, the aim was to correlate NVC findings with serum levels of autoantibodies (Abs) against extractable nuclear antigen (ENA) detected in UCTD.Methods:Files of fourty-six MCTD patients (Kasukawa’s criteria) (mean age 42.8±16 SD years), fourty-seven UCTD patients (mean age 47.7±16.1 SD years), fifty-one PRP (mean age 45.9±17.3 SD years) were retrospectively evaluated in the study. Among UCTD and MCTD patients 95% of both showed Raynaud’s phenomenon. Main NVC parameters (i.e. dilated capillaries, giant capillaries, microhemorrhages, abnormal shapes and number of capillaries) and related semiquantitative scale (score 0–3 for every parameter), were analyzed and compared between the two distinct CTD groups and PRP. Furthermore, ENA Abs (in particular, Ro/SSA, La/SSB, Scl70 and Jo1) were evaluated. The CTD patients were receiving different immunosuppressive treatments. Statistical analysis was performed by non-parametric tests.Results:Among UCTD group, 36% of patients showed a normal NVC pattern, 53% had non-specific NVC abnormalities and 11% had a scleroderma like-pattern. The latter was significantly more frequent in MCTD than in UCTD (p<0.001), in fact 22 out of 46 (48%) MCTD patients presented a scleroderma-like pattern. On the other hand, normal pattern or non-specific NVC abnormalities were respectively found in 9% and 43% MCTD patients. Therefore, CTD patients showing giant capillaries, abnormal shapes (i.e. angiogenesis) and lower capillary density were significantly more affected by MCTD than UCTD (p<0.001). Finally, the absolute number of capillaries was found significantly lower in MCTD versus UCTD patients (mean 7±1.7 SD vs mean 9.2±1 SD, respectively, p<0.001). Not any statistical correlation was observed between NVC parameters and specific Abs ENA in UCTD. PRP showed a normal NVC pattern in 2% and non-specific capillary abnormalities in 98%, (including dilated capillaries and microhemorrhages).Conclusion:NVC features in UCTD patients seem very close to the pattern observed in PRP (mostly non-specific capillary abnormalities), conversely in MCTD the scleroderma-like pattern was found significantly prevalent together with a significant capillary number reduction. The transition from the scleroderma-like to the scleroderma pattern (mean systemic sclerosis) is matter of actual investigation.References:[1]Cutolo M. et al. Best Pract Res Clin Rheumatol 2008; 22:1093-108.[2]Sulli A, Ann Rheum Dis. 2008;67:885-7.[3]Smith V. et al. Autoimmunity Reviews 2020; 19:102458.[4]De Holanda Mafaldo DA, et al. Lupus. 2007; 16:254–8.[5]Smith V, et al. Ann Rheum Dis 2010; 69: 1092-96.[6]Antunes M, et al. RMD Open. 2019, 26;4.Disclosure of Interests:None declared

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