scholarly journals Detection of Specific Antinuclear Reactivities in Patients with Negative Anti-nuclear Antibody Immunofluorescence Screening Tests

2002 ◽  
Vol 48 (12) ◽  
pp. 2171-2176 ◽  
Author(s):  
Ilse EA Hoffman ◽  
Isabelle Peene ◽  
Eric M Veys ◽  
Filip De Keyser

Abstract Background: For detection of anti-nuclear antibodies (ANAs) and antibodies to extractable nuclear antigens (ENAs), samples frequently are screened with indirect immunofluorescence (IIF); further determination of anti-ENA antibodies is performed only when the result is positive. However, because anti-ENA reactivities are found in samples with low fluorescence intensities, we determined anti-ENA antibodies in samples with negative IIF and thus calculated the sensitivity of IIF for specific ANAs. Methods: We collected 494 samples consecutively referred by rheumatologists for routine ANA testing. IIF on HEp-2 and HEp-2000 (HEp-2 cells transfected with Ro60 cDNA) and line immunoassay (LIA) for the detection of specific ANAs were performed on all samples. Results: Fluorescence intensities and patterns on HEp-2 were strongly correlated with those on HEp-2000 [Spearman ρ = 0.852 (P <0.001) and 0.838 (P <0.001), respectively]. Sixty-eight of 494 samples were positive on LIA, of which only 72% (confidence interval, 68–76%) were detected with HEp-2 and 75% (confidence interval, 70–78%) with HEp-2000. Of 291 samples negative on both substrates, 12 were positive on LIA. Connective tissue diseases were diagnosed in four of these patients and suspected in at least three others. Conclusion: The HEp-2 and HEp-2000 substrates perform comparably for fluorescence intensities and patterns and for detecting specific ANAs, but some patients with negative IIF show reactivity on LIA. We recommend testing for fine reactivities, regardless of the IIF result, when the clinical suspicion for rheumatic connective tissue disease is high.

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Sheilla Achieng ◽  
John A Reynolds ◽  
Ian N Bruce ◽  
Marwan Bukhari

Abstract Background/Aims  We aimed to establish the validity of the SLE-key® rule-out test and analyse its utility in distinguishing systemic lupus erythematosus (SLE) from other autoimmune rheumatic connective tissue diseases. Methods  We used data from the Lupus Extended Autoimmune Phenotype (LEAP) study, which included a representative cross-sectional sample of patients with a variety of rheumatic connective tissue diseases, including SLE, mixed connective tissue disease (MCTD), inflammatory myositis, systemic sclerosis, primary Sjögren’s syndrome and undifferentiated connective tissue disease (UCTD). The modified 1997 ACR criteria were used to classify patients with SLE. Banked serum samples were sent to Immune-Array’s CLIA- certified laboratory Veracis (Richmond, VA) for testing. Patients were assigned test scores between 0 and 1 where a score of 0 was considered a negative rule-out test (i.e. SLE cannot be excluded) whilst a score of 1 was assigned for a positive rule-out test (i.e. SLE excluded). Performance measures were used to assess the test’s validity and measures of association determined using linear regression and Spearman’s correlation. Results  Our study included a total of 155 patients of whom 66 had SLE. The mean age in the SLE group was 44.2 years (SD 13.04). 146 patients (94.1%) were female. 84 (54.2%) patients from the entire cohort had ACR SLE scores of ≤ 3 whilst 71 (45.8%) had ACR SLE scores ≥ 4. The mean ACR SLE total score for the SLE patients was 4.85 (SD 1.67), ranging from 2 to 8, with mean disease duration of 12.9 years. The Sensitivity of the SLE-Key® Rule-Out test in diagnosing SLE from other connective tissue diseases was 54.5%, specificity was 44.9%, PPV 42.4% and NPV 57.1 %. 45% of the SLE patients had a positive rule-out test. SLE could not be ruled out in 73% of the MCTD patients whilst 51% of the UCTD patients had a positive Rule-Out test and >85% of the inflammatory myositis patients had a negative rule-out test. ROC analysis generated an AUC of 0.525 illustrating weak class separation capacity. Linear regression established a negative correlation between the SLE-key Rule-Out score and ACR SLE total scores. Spearman’s correlation was run to determine the relationship between ACR SLE total scores and SLE-key rule-out score and showed very weak negative correlation (rs = -0.0815, n = 155, p = 0.313). Conclusion  Our findings demonstrate that when applied in clinical practice in a rheumatology CTD clinic setting, the SLE-key® rule-out test does not accurately distinguish SLE from other CTDs. The development of a robust test that could achieve this would be pivotal. It is however important to highlight that the test was designed to distinguish healthy subjects from SLE patients and not for the purpose of differentiating SLE from other connective tissue diseases. Disclosure  S. Achieng: None. J.A. Reynolds: None. I.N. Bruce: Other; I.N.B is a National Institute for Health Research (NIHR) Senior Investigator and is funded by the NIHR Manchester Biomedical Research Centre. M. Bukhari: None.


Author(s):  
Michelle Elaine Orme ◽  
Carmen Andalucia ◽  
Sigrid Sjölander ◽  
Xavier Bossuyt

AbstractObjectivesTo compare indirect immunofluorescence (IIF) for antinuclear antibodies (ANA) against immunoassays (IAs) as an initial screening test for connective tissue diseases (CTDs).MethodsA systematic literature review identified cross-sectional or case-control studies reporting test accuracy data for IIF and enzyme-linked immunosorbent assays (ELISA), fluorescence enzyme immunoassay (FEIA), chemiluminescent immunoassay (CLIA) or multiplex immunoassay (MIA). The meta-analysis used hierarchical, bivariate, mixed-effect models with random-effects by test.ResultsDirect comparisons of IIF with ELISA showed that both tests had good sensitivity (five studies, 2321 patients: ELISA: 90.3% [95% confidence interval (CI): 80.5%, 95.5%] vs. IIF at a cut-off of 1:80: 86.8% [95% CI: 81.8%, 90.6%]; p = 0.4) but low specificity, with considerable variance across assays (ELISA: 56.9% [95% CI: 40.9%, 71.5%] vs. IIF 1:80: 68.0% [95% CI: 39.5%, 87.4%]; p = 0.5). FEIA sensitivity was lower than IIF sensitivity (1:80: p = 0.005; 1:160: p = 0.051); however, FEIA specificity was higher (seven studies, n = 12,311, FEIA 93.6% [95% CI: 89.9%, 96.0%] vs. IIF 1:80 72.4% [95% CI: 62.2%, 80.7%]; p < 0.001; seven studies, n = 3251, FEIA 93.5% [95% CI: 91.1%, 95.3%] vs. IIF 1:160 81.1% [95% CI: 73.4%, 86.9%]; p < 0.0001). CLIA sensitivity was similar to IIF (1:80) with higher specificity (four studies, n = 1981: sensitivity 85.9% [95% CI: 64.7%, 95.3%]; p = 0.86; specificity 86.1% [95% CI: 78.3%, 91.4%]). More data are needed to make firm inferences for CLIA vs. IIF given the wide prediction region. There were too few studies for the meta-analysis of MIA vs. IIF (MIA sensitivity range 73.7%–86%; specificity 53%–91%).ConclusionsFEIA and CLIA have good specificity compared to IIF. A positive FEIA or CLIA test is useful to support the diagnosis of a CTD. A negative IIF test is useful to exclude a CTD.


2021 ◽  
Vol 11 (Number 1) ◽  
pp. 60-65
Author(s):  
Abu Saleh Shimon ◽  
Mahjuba Umme Salam ◽  
Monharul Islam Bhuiyan ◽  
Mashuq Ahmad Jumma ◽  
Imran Hussain ◽  
...  

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.


Author(s):  
Gavin Spickett

This chapter covers the presentation, immunogenetics, immunopathology, diagnosis, treatment, and testing for a range of connective tissue diseases. It covers a range of rheumatic disorders, from rheumatoid arthritis to Raynaud’s phenomenon, and also covers the undifferentiated diseases, overlap syndromes, and mixed connective tissue disease.


2020 ◽  
Vol 48 (1) ◽  
pp. 18-25
Author(s):  
José Enrique Oliva Menacho ◽  
Jorge Luis Arroyo-Acevedo ◽  
José Arturo Oliva-Candela ◽  
Marco Antonio García-Hjarles ◽  
Lester Domínguez-Huarcaya

1981 ◽  
Vol 9 (1) ◽  
pp. 144-145
Author(s):  
SOHRAB DAHI ◽  
GEORGE NAXAKIS ◽  
CHRISTINE M. WALLIS ◽  
ALEXANDER J. MacGILLIVRAY

2020 ◽  
pp. 004947552096274
Author(s):  
U Pratap ◽  
M Ravindrachari ◽  
A RamyaPriya ◽  
Pampa Ch. Toi ◽  
R Manju

Connective tissue diseases and infections are amongst the causes for organising pneumonia. However, organising pneumonia preceding other connective tissue disease manifestations is rare. Mycobacterium tuberculosis is rarely associated with organising pneumonia. We report such a case. A 50-year-old diabetic male, a roadside shop keeper, a current smoker presented with fever, breathlessness, cough and weight loss for four months. Chest radiography demonstrated areas of consolidation with halo signs. Anti-nuclear antibody blot was positive for Scl-70 and Jo-1 suggestive of a syndrome of systemic sclerosis and polymyositis overlap. Fibre-optic bronchoscopy guided lung biopsy was suggestive of organising pneumonia, and broncho-alveolar lavage detected Mycobacterium tuberculosis. Mycobacterium tuberculosis should be investigated as an aetiology of organising pneumonia, as this may occur in unestablished cases of connective tissue disease even before clinical and radiological manifestations appear, as response can be achieved with anti-tuberculosis therapy alone, without additional use of systemic steroids.


RMD Open ◽  
2019 ◽  
Vol 4 (Suppl 1) ◽  
pp. e000786 ◽  
Author(s):  
Margarida Antunes ◽  
Carlo Alberto Scirè ◽  
Rosaria Talarico ◽  
Tobias Alexander ◽  
Tadej Avcin ◽  
...  

The term ‘undifferentiated connective tissue disease’ (UCTD) is generally used to describe clinical entities characterised by clinical and serological manifestations of systemic autoimmune diseases but not fulfilling the criteria for defined connective tissue diseases (CTDs). In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the ERN ReCONNET project, aimed at evaluating existing clinical practice guidelines (CPGs) or recommendations.No specific CPG on UCTD were found, potential areas of intervention are absence of a consensus definition of UCTD, need for specific monitoring and therapeutic protocols, stratification of UCTD based on the risk of developing a defined CTD and preventive measure for the future development of a more severe condition.Patients feel uncertainty regarding the name of the disease and feel the need of a better education and understanding of these conditions and its possible changes over time.


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