Importancia del patrón moteado fino denso y de los anticuerpos anti-DFS70 en el diagnóstico de enfermedades autoinmunitarias del tejido conectivo / Importance of the dense fine speckled pattern and anti-DFS70 antibodies for the diagnosis of systemic autoimmune rheumatic diseases

No disponible

[The main stages in the history of systemic lupus erythematosus]. / Le principali tappe nella storia del lupus eritematoso sistemico.

Systemic lupus erythematosus can be considered the most characteristic and important among the connective tissue diseases. In this short review the main stages of its history are sketched, from the introduction of the term "lupus", traditionally attributed to Roger Frugardi, in 1230 (but in fact already documented in the 10th century) to the actual knowledge of its clinical and laboratory aspects. Initially considered exclusively of dermatological interest, the first to describe a systemic form with visceral involvement were Moriz Kohn Kaposi and William Osler. Significant contribution was also given by serological diagnosis, and in particular, by the identification of specific markers of disease, such as anti-native DNA and anti-Sm antibodies, allowing early diagnosis and the establishment of an adequate therapy.

Autoantibodies to heterogeneous nuclear ribonucleoproteins.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are among the most abundant proteins in the eukaryotic cell nucleus and play a direct role in several aspects of the RNA life including splicing, export of the mature RNAs and translation. To date, approximately 30 proteins have been identified. A growing body of evidence points to hnRNPs as an important target of the autoimmune response in rheumatic diseases. Autoantibodies to A and B proteins of the hnRNP complex have been detected in late 1980s in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Beyond their role as diagnostic test in clinical practice, these autoantibodies are starting to be regarded as important tools to obtain deeper insight into the pathogenesis of autoimmune rheumatic diseases. Furthermore, new anti-hnRNP antibodies have been recognized in the last ten years extending the spectrum of anti-hnRNP reactivity in different autoimmune disorders.

Anti-Ro/SSA and La/SSB antibodies.

The Ro/La system is considered as an heterogeneous antigenic complex, constituted by three different proteins (52 kDa Ro, 60 kDa Ro and La) and four small RNAs particles. Anti-Ro/SSA are the most prevalent specificity among many autoimmune diseases, such as systemic lupus erythematosus (SLE), SS/SLE overlap syndrome, subacute cutaneous LE (SCLE), neonatal lupus and primary biliary cirrhosis. In contrast, anti-La/SSB is more associated with Sjögren's syndrome (SS). The differences between 52 kDa, 60 kDa Ro and La could explain why different assays did not show equivalent performance in anti-Ro and anti-La autoantibodies detection. The RNA precipitation assay had the highest sensitivity and specificity, usually considered as the reference methods. CIE is considered the most reliable to detect anti-Ro/SSA antibodies in routine practice, performing better than immunoblotting (IB) and some ELISAs. It shows a high sensitivity (89%) and specificity (100%). ELISA is generally considered a safe, rapid, sensitive and specific tecnique. Therefore, its high sensitivity often corresponds to a very low clinical specificity and the assay can give false positive results. Therefore, it is very important to search anti-Ro and anti-La only in selected patients, using the assay with high specificity and good predictive value, in order to have clinically significant and true positive results.

Anti-scl-70.

OBJECTIVE: To develop an overview focusing on the utility of anti-Scl-70 autoantibody determinations in the rheumatic diseases. METHODS: Articles from electronic literature searches were retrieved, critiqued and data were extracted and pooled on anti-Scl-70 (topoisomerase I) in relation to history, optimal tests used for its detection, sensitivity, specificity, positive and negative likelihood ratios, indications, interpretation and pitfalls. RESULTS: Anti-Scl 70 antibodies are very useful in distinguishing systemic sclerosis (SSc) patients from healthy controls, from patients with other connective tissue diseases, and from unaffected family members. Among patients with SSc, anti-Scl-70 positivity is useful in predicting those at higher risk for diffuse cutaneous involvement and interstitial fibrosis/restrictive lung disease, though the latter has not been universally observed. Of the four different techniques notably immunodiffusion, immunoblotting, immunoprecipitation and enzyme-linked immunosorbent assay (ELISA) used to assay anti-Scl-70, immunodiffusion has been the most extensively validated. ELISAs are somewhat less specific than other techniques, especially in distinguishing SSc patients from those with other rheumatic diseases, though newer generation ELISAs have been developed to overcome the problem of low specificity inherent with the traditional techniques. As of yet, the need for serial testing of anti-Scl-70 has not been established. CONCLUSIONS: Evidence-based guidelines suggest that anti-Scl-70 antibodies are very useful in the diagnosis and clinical management of SSc patients and also to establish prognosis in these patients, particularly those with diffuse skin involvement.

Anti-Jo-1 antibodies.

Anti-Jo-1 antibody is a myositis specific autoantibody most commonly found in patients with idiopathic inflammatory myopathies (IIM). This antibody is directed against the histidyl-tRNA synthetase which catalyses the binding of the histidine to its cognate tRNA during protein synthesis. It can be considered a specific marker of IIM, predominantly found in 20-30% of patients with PM and in the 60-70% of those with interstitial pulmonary fibrosis. These antibodies are also found in DM, although less frequently than in PM, and are rare in children with PM or DM and in other connective tissue diseases.ELISA, CIE and immunoblotting are highly specific and sensitive techniques for testing anti-Jo-1 antibodies. The detection of this antibody is particularly useful in diagnosis and classification of IIM. Moreover, anti-Jo-1 serum levels strongly correlate with disease activity representing a good marker for disease monitoring.

Antinuclear antibody- and extractable nuclear antigen-related diseases.

In 1948, the observation of the LE cell phenomenon in a patient with systemic lupus erythematosus (SLE) began the discovery of a broad variety of autoantibodies directed to nuclear antigens called antinuclear antibodies (ANA). Nowadays, different ANA serve as important diagnostic parameters for differentiating most of the connective tissue diseases, such as SLE, neonatal lupus syndromes, Sjögren's syndrome, scleroderma, autoimmune myositis, mixed connective tissue disease and other overlaps. This overview summarizes the history of ANA and their detection methods, in part to introduce the subsequent papers dealing with special topics of ANA-related diseases in this issue. Furthermore, the pathogenic role of these autoantibodies in targeting non-organ-specific intracellular antigens as a functional important constituent of a subcellular particle or multimolecular complex is addressed. Notably, some of these autoantibodies have functioned as significant tools for cell biologists to elucidate the subcellular structures and functions of these autoantigens. In the future, we can expect further advances to answer such important questions as why these antigens are targets of autoantibodies, what is their pathogenic impact and what are the triggers of autoimmunity?

Setting the scene: a historical and personal view of immunologic diseases, autoimmunity and ANA.

Dr. Friou reviews here his research experiences in immunology beginning over fifty years ago, and dealing with his early background experience with group A streptococcus, antihyaluronidase, and rheumatic fever, and cell mediated responses in Boeck's sarcoid. Details of his introduction of the immunofluorescent technique of Harvard Prof. Albert Coons into the SLE-ANA area, with the complexities and difficulties of early involvement with the technique are described. The simple, but extremely clever experiment of Prof. Miescher of Geneva which created an ideal situation for the application of immunofluorescence to the SLE area is described. Technical details of the earliest immunofluorescent ANA studies are presented, together with firm data that these early studies, which included many human sera and studies of the nature of the antibody target, had been completed by February 21, 1957, well in advance of any other laboratory. Important subsequent related studies from international laboratories are reviewed.