Performance of Antinuclear Antibodies for Classifying Systemic Lupus Erythematosus: A Systematic Literature Review and Meta‐Regression of Diagnostic Data

Objective

To review the published literature on the performance of indirect immunofluorescence (IIF)–HEp‐2 antinuclear antibody (ANA) testing for classification of systemic lupus erythematosus (SLE).

Methods

A systematic literature search was conducted in the Medline, Embase, and Cochrane databases for articles published between January 1990 and October 2015. The research question was structured according to Population, Intervention, Comparator, Outcome (PICO) format rules, and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) recommendations were followed where appropriate. Meta‐regression analysis for diagnostic tests was performed, using the ANA titer as independent variable, while sensitivity and specificity were dependent variables.

Results

Of 4,483 publications screened, 62 matched the eligibility criteria, and another 2 articles were identified through reference analysis. The included studies comprised 13,080 SLE patients in total, of whom 12,542 (95.9%) were reported to be IIF‐ANA positive at various titers. For ANA at titers of 1:40, 1:80, 1:160, and 1:320, meta‐regression gave sensitivity values of 98.4% (95% confidence interval [95% CI] 97.6–99.0%), 97.8% (95% CI 96.8–98.5%), 95.8% (95% CI 94.1–97.1%), and 86.0% (95% CI 77.0–91.9%), respectively. The corresponding specificities were 66.9% (95% CI 57.8–74.9%), 74.7% (95% CI 66.7–81.3%), 86.2% (95% CI 80.4–90.5%), and 96.6% (95% CI 93.9–98.1%), respectively.

Conclusion

The results of this systematic literature review and meta‐regression confirm that IIF‐ANAs have high sensitivity for SLE. ANAs at a titer of 1:80 have sufficiently high sensitivity to be considered as an entry criterion for SLE classification criteria, i.e., formally test other classification criteria for SLE only if ANAs of at least 1:80 have been found.

     

Prediction,identification and progression of histopathological liver disease activity in children with intestinal failure

1. Download : Download high-res image (191KB)
2. Download : Download full-size image

     

Discovery of endogenous catecholamines in lymphocytes and evidence for catecholamine regulation of lymphocyte function via an autocrine loop.

Evidence has been obtained that catecholamines and their metabolites are present in single lymphocytes and extracts of T- and B-cell clones by use of capillary electrophoresis with electrochemical detection. Pharmacological inhibition of tyrosine hydroxylase reduces observed catecholamine levels, suggesting catecholamine synthesis by lymphocytes. Intracellular dopamine levels are shown to be increased by extra-cellular dopamine, suggesting a cellular-uptake mechanism. Furthermore, incubation with either dopamine or L-dihydroxyphenylalanine, a precursor of dopamine, results in a dose-dependent inhibition of lymphocyte proliferation and differentiation. Together, these results suggest the presence of an autocrine loop whereby lymphocytes down-regulate their own activity.     

Surveillance and response: Tools and approaches for the elimination stage of neglected tropical diseases

The presentation of the World Health Organization (WHO)’s roadmap for neglected tropical diseases (NTDs) in January 2012 raised optimism that many NTDs can indeed be eliminated. To make this happen, the endemic, often low-income countries with still heavy NTD burdens must substantially strengthen their health systems. In particular, they need not only to apply validated, highly sensitive diagnostic tools and sustainable effective control approaches for treatment and transmission control, but also to participate in the development and use of surveillance–response schemes to ensure that progress made also is consolidated and sustained. Surveillance followed-up by public health actions consisting of response packages tailored to interruption of transmission in different settings will help to effectively achieve the disease control/elimination goals by 2020, as anticipated by the WHO roadmap. Risk-mapping geared at detection of transmission hotspots by means of geospatial and other dynamic approaches facilitates decision-making at the technical as well as the political level. Surveillance should thus be conceived and developed as an intervention approach and at the same time function as an early warning system for the potential re-emergence of endemic infections as well as for new, rapidly spread epidemics and pandemics.     

Does tumour necrosis factor‐α inhibitor infliximab induce histological resolution of pulmonary sarcoid granulomas?

Background: Sarcoid granuloma formation involves the orchestration of cytokines and chemokines, which modulate the host's immune response to the antigen stimulus. The release of cytokines enhances expression of the pro‐inflammatory cytokine tumour necrosis factor‐α (TNF), which plays a crucial role in the formation of sarcoid granuloma, being released from T‐lymphocytes and alveolar macrophages. Objective: The aim of this study was to evaluate the effect of infliximab in a case of pulmonary sarcoidosis using a histological approach. Materials and Methods: A 44‐year‐old man with biopsy verified chronic pulmonary sarcoidosis being resistant to treatment with corticosteroids and cell cycle inhibitors. Persisting disease activity was confirmed by declining lung function tests and a positive fluorine‐18‐fluorodeoxyglucose–positron emission tomography scan. The patient was treated with a single course of infliximab 3‐mg/kg body weight; 11 days later, a single lung transplantation was performed. Immunohistological staining with the macrophage marker CD68 was performed on lung tissue and mediastinal lymph node tissue from both the initial diagnostic evaluation (prior to infliximab) as well as from the explanted lung (after infliximab). Results: Biopsy specimens from lung and mediastinal lymph nodes prior to infliximab demonstrated sarcoid granulomas, and staining with CD68 showed dense infiltration by macrophages (epithelioid cells) in the central part of the granulomas. In contrast, biopsies from the explanted lung after infliximab demonstrated acellular sarcoid granulomas with central amorphous masses, and staining with CD68 showed complete absence of macrophages. Conclusions: In this patient, the TNF inhibitor infliximab appeared to induce resolution of sarcoid granulomas starting with disappearance of macrophages probably caused by cell lysis or apoptosis. Please cite this paper as: Milman N, Andersen CB, Baslund B, Loft A and Iversen M. Does tumour necrosis factor‐α inhibitor infliximab induce histological resolution of pulmonary sarcoid granulomas? The Clinical Respiratory Journal 2007; 1:106–113.     

Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated β-cell maturation

The endocrine pancreas expands markedly in the first postnatal days and the insulin producing β-cells initiate a functional maturation preceded by a morphological change of the islets of Langerhans. Trefoil factor 3 (TFF3) is a secreted peptide expressed in intestinal epithelia, where it promotes migration, but its role in the pancreas is not characterized. The aim of this study was to examine the expression and function of TFF3 in perinatal rat pancreas, ex vivo cultured fetal rat pancreas and in the rat β-cell line INS-1E.

Control or gestational low-protein diet perinatal rat pancreas was harvested at embryonic day 20 (E20), day of birth (P0) and postnatal day 2 (P2). TFF3 mRNA was upregulated 4.5-fold at P0 vs. E20 and downregulated again at P2. In protein-undernourished pups induction of TFF3 at P0 was further increased to 9.7-fold and was increased at P2. TFF3 caused tyrosine phosphorylation of EGFR in INS-1E β-cells, and purified recombinant TFF3 increased both attachment and spreading of INS-1E β-cells. In ex vivo cultures of collagenase digested fetal rat pancreas, a model of perinatal β-cell maturation, TFF3 increased cellular spreading as well as insulin mRNA levels. TFF3 also increased the expression of Pref1/Dlk1 that shares similarities in expression and regulation with TFF3.

These results suggest that TFF3 may promote adhesion and spreading of cells to accelerate β-cell maturation. This study indicates a functional role for TFF3 in pancreatic β-cell maturation in the perinatal period, which is altered by low protein diet during gestation.