Tag Archives: autoantibodies

Abstract

BACKGROUND:

Systematic reviews and meta-analysis are essential tools to accurately and reliably summarize evidence, and can be used as a starting point for developing practice guidelines for the diagnosis and treatment of patients.

AIM:

To estimate the diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) to detect anti-BP180 and anti-desmoglein 3 (Dsg3) autoantibodies in the diagnosis of autoimmune blistering skin diseases.

METHODS:

A Medline search of English written articles, published between 1994 and 2011, reporting data on the sensitivity and specificity of diagnostic tests was conducted using the following search terms: “BP180 autoantibodies”, “Dsg3 autoantibodies”, and “enzyme linked immunosorbent assay”. The selected articles have been evaluated according to the quality of the statistical methods used to calculate diagnostic accuracy (definition of cutoff value, use of ROC curves, and selection of control cases). The meta-analysis was performed using a summary ROC (SROC) curve and a random-effect model to independently combine sensitivity and specificity across studies.

RESULTS:

The search yielded 69 publications on BP180 autoantibodies and 178 on Dsg3 autoantibodies. A total of 30 studies met the inclusion criteria: 17 provided data on the assays to detect autoantibodies to BP180 in a sample of 583 patients with bullous pemphigoid (BP), while 13 studies provided data on the assays to search for anti-Dsg3 autoantibodies in a sample of 1058 patients with pemphigus vulgaris (PV). The 17 studies on BP180 autoantibodies yielded a pooled sensitivity of 0.87 (95% confidence interval (CI) 0.85 to 0.89) and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The area under the curve (AUC) for the SROC curve was 0.988, and the summary diagnostic odds ratio was 374.91 (CI, 249.97 to 562.30). The 13 studies on Dsg3 autoantibodies which met the inclusion criteria, yielded a pooled sensitivity of 0.97 (CI, 0.95 to 0.98), and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The AUC for the SROC curve was 0.995 and the summary diagnostic odds ratio was 1466.11 (95% CI, 750.36 to 2864.61).

CONCLUSIONS:

Results of the meta-analysis demonstrated that ELISA tests for anti-BP180 and anti-Dsg3 autoantibodies have high sensitivity and specificity for BP and PV, respectively, and can be used in daily laboratory practice for the initial diagnosis of autoimmune blistering skin diseases.
PMID: 22781589 [PubMed – as supplied by publisher] (Source: Autoimmunity Reviews)

from MedWorm: Pemphigus http://www.medworm.com/index.php?rid=6303276&cid=c_297_3_f&fid=34528&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2FPubMed%2F22781589%3Fdopt%3DAbstract

by Sarah Brenner, MD, Jacob Mashiah, MD, Einat Tamir, MD, Ilan Goldberg, MD and Yonit Wohl, MD, Department of Dermatology, Tel Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Israel

Pemphigus is generally considered to stem from a genetic predisposition to the disease triggered and/or aggravated by one or more external factors. An acronym has been suggested from the name of the disease, PEMPHIGUS, to encompass those factors:

by Edward Tenner, M.D.

INTRODUCTION

The autoimmune bullous skin diseases, pemphigus (with major subsets pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus) and the more common bullous pemphigoid (with variant disease phenotypes of cicatricial pemphigoid and gestational pemphigoid) each may have ocular manifestations.

By Robert Jordon, M.D.
Professor and Chairman, Department of Dermatology,
University of Texas
Houston, Texas

Historical Perspective

The term pemphigus was most likely in use in the ancient world, but the first recorded instance was by Hippocrates (460-370 BC) who described pemphigoid fever as “pemphigodes pyertoi.” Galen (AD 13 1-201) named a pustular disease of the mouth as “febris pemphigodes.” In 1637, Zacutus again uses the term “febris pemphigodes” to describe patients with blisters of short duration. DeSauvages (1760) described patients with high fever and blisters of short duration as having “pemphigus maior.” None of the above conditions is considered to be true pemphigus, as their disease was of short duration and all patients recovered.

 

By Professor Martin M Black, MD

Pemphigus and its variants are rare autoimmune disorders characterized by loss of cell to cell cohesion between keratinocytes leading to intra-epidermal blistering. In all types of pemphigus, antibodies are directed against antigens in the intercellular substance between keratinocytes and in a substantial number of active cases, these pemphigus antibodies can be detected in the general blood circulation.

Pempigus vulgaris (PV) is characterized by flaccid blistering and erosions of the skin and mucous membranes. Involvement within the mouth may often precede the skin erosions and may persist even long after skin lesions subside. It is therefore important to remember that involvement of the oral cavity may take the patient to see dental surgeon, rather than a dermatologist in the first instance. However, in pemphigus foliaceus (PF) the blistering tends to be more superficial than in the vulgaris form of pemphigus and the mucous membrane areas are not involved.

For many years, London, one of the largest cities in the world, has been truly international, with large populations of different ethnic groups living together within a 50 mile radius. This multi ethnicity provides an ideal opportunity to study the epidemiology of pemphigus and provide information on ethnic groups and numbers of involvement. We have recently surveyed our 140 patients of pemphigus who attend our St. John’s Institute for Diseases of the Skin. In our group, the male to female ratio was 1:1.12 (77 F, 63 M) and the mean age of disease onset was 44 years. This of course, is in the prime of adult life and has important economic consequences for patient sufferers, particularly if the disease is severe and the treatment likely to be longstanding. In our patients, the ethnic break-up of our group was British 51 (36.4%), Asian (Indian subcontinent) 46 (32.8%). This is quite a high figure and corroborates other evidence that pemphigus is much more common in patients living in the Indian subcontinent countries. Of Afro-caribbean countries, 15 (10.7%) had pemphigus, Middle-East 12 (8.5%) and curiously, Jewish 9 (6.4%) is rather low, as all the text books state that pemphigus is much more common in those of Jewish ancestry. Others of mixed ethnicity are fewer in number and comprise 2 Greeks and 2 Chinese. This evidence certainly would indicate the genetic factors and have an important role in predisposing individuals to developing pemphigus. It is therefore an opportunity for us to develop this theme further and we will be doing this over the next few years, looking at the genetic haplo types.

For over 25 years, our immunodermatopathological laboratory at our Institute has specialized in diagnosis of auto-immune bullous diseases. We have developed considerable experience with immunofluoresence techniques to detect the presence of antibodies in the skin by the direct method and in the serum by indirect methods. It is now well known that the PF antigen is a transmembrane glycoprotein called desmoglein 1 (Dsg1) and the PV angiten is termed desmoglein 3 (Dsg3). These desmogleins are adhesion molecules belonging to the cadherin family of cell adhesion substances and are very important in keeping the covering of our skin together.

A recent innovation has been the introduction of an antigen specific ELISA test in the diagnosis of pemphigus. The patient’s serum is tested on ELISA plates pre-coated with recombinant proteins of the ectodomain of Dsg1 or Dsg3 antigens (Medical and Biological laboratories Co, Ltd, Nagoya, Japan). Thus specific antibodies directed against Dsg1 or Dsg3 antigens can be detected by this technique.

It was seen that 61% of patients with PV have antibodies to Dsg 1 in addition to Dsg3, and presence of both the antibody types was associated with severe cutaneous and mucosal involvement, while presence of only Dsg3 autoantibodies was associated with pemphigus limited to mucosal surfaces (mainly oral). The proportion of Dsg1 positive PV patients was higher in the Asian ethnic group when compared to their British counterparts. The severity of the skin and oral disease is influenced by the quantities of Dsg1 and Dsg3 antibodies present in a patient.

Conclusion

Whether ELISA plate techniques will eventually overtake immunofluoresence in the diagnosis of pemphigus and related diseases is too early to say, but they are an important advance and enable large numbers of samples to be read quite quickly. I am sure those of you who are interested in pemphigus will see much more on this in the future about diagnostic techniques. Clearly, accurate diagnosis will ultimately lead to the potential of good targeted therapies.

by Thierry Olivry, DrVet, PhD, DipACVD, DipECVD,
Associate Professor of Dermatology, Department of Clinical Sciences,
College of Veterinary Medicine, NC State University,
Raleigh, North Carolina,
and Adjunct Clinical Associate Professor of Dermatology, Department of Dermatology,
School of Medicine, University of North Carolina,
Chapel Hill, North Carolina

Autoimmune blistering skin diseases first were identified in companion animals twenty five years ago, with the description of two dogs affected with pemphigus vulgaris (PV). Two years later, the first cases of pemphigus foliaceus (PF) were recognized in canine patients. These two diseases represent the main forms of animal pemphigus being diagnosed by veterinarians.

Surprisingly, whereas the main form of pemphigus affecting human individuals is pemphigus vulgaris (PV), this entity is extremely rare in dogs with less than 50 cases being reported in veterinary medical journals. This deep pemphigus variant also has been recognized, albeit very sporadically, in rare cats and horses.

By Grant J. Anhalt, M.D.
Johns Hopkins Dermatology

I will attempt to clarify what we know about the antibody response in various forms of pemphigus and how the distribution of the targeted antigens affects the location of lesions. The synthesis of this work has been proposed by Dr. John Stanley, with key published advances from Dr. Masa Amagai and Mai Mahoney, Ph.D., P. Koch and others. John Stanley refers to his concept as the “desmoglein compensation hypothesis”. The key to this hypothesis is the desmogleins (pemphigus antigens) are key adhesion molecules that keep cells attached to each other. In some areas of the body, there are two desmogleins present, and both have to be damaged to cause cell detachment – in some areas only one desmoglein may be present at some level in the skin or mucous membrane, and there only one desmoglein has to be damaged to cause cell detachment.

By Sergei A. Grando, MD, PhD, DSci
Professor of Dermatology
University of California Davis

The Need for Alternative Therapies for Pemphigus. In autoimmune pemphigus, systemic glucocorticosteroid treatment is life saving but may cause severe side effects. Pemphigus patients therefore need drugs that will provide safer treatment of their disease by replacing systemic use of glucocorticoid hormones such as Prednisone. Development of non-hormonal treatment is hampered by a lack of clear understanding of the mechanisms leading to pemphigus lesions. Pemphigus can be associated with myasthenia gravis, and in both diseases the autoantibodies to acetylcholine receptors are produced, suggesting a common mechanism of disease development.

by Luis A. Diaz, M.D.
Professor and Chairman Department of Dermatology Medical College of Wisconsin
Milwaukee, Wisconsin

Pemphigus foliaceous (PF) one of the major clinical variants of pemphigus, is characterized by superficial blisters and anti-epidermal autoantibodies. The epidermal antigen with which PF autoantibodies react is a desmosomal protein designated desmoglein 1 (dsg1). There are two forms of PF-a sporadic form which has worldwide distribution, and an endemic form, which has only been observed in certain rural areas of Brazil, Columbia and Tunisia.