Journal of the American Academy of Dermatology
A practical guide for serologic evaluation of autoimmune connective tissue diseases☆,☆☆
Section snippets
BIOLOGY OF THE ANTIBODY SPECIFICITY
Patients with CTD have an autoimmune phenomenon that results in the production of antibodies against several self-antigens. These autoantibodies are directed against all cellular components, that is, nuclear, cytoplasmic, and cell membrane molecules. The binding of these antibodies to commercially available tissue extracts is the basis for serologic testing. Whether these antibodies play a role in the pathogenesis of the clinical manifestations of the disease is suspected but not confirmed with
TECHNIQUES FOR SEROLOGIC TESTING
The methods for the detection of the various antibodies have changed over the past few decades. Immunologic techniques that are commonly used during each time period have been utilized for the detection of these antibodies. For example, radioimmunoassay and immunoelectrophoresis were commonly used in the past.30, 31, 32, 33, 34, 35, 36 Radial immunodiffusion and immunofluorescence8, 10, 30, 32, 37, 38, 39, 40, 41, 42 remain of important value although both (especially the former) are being
ANTIBODIES TO DNA
Serum DNA antibodies may recognize nDNA (double-stranded) or denatured ssDNA by testing, depending on the type of epitope within the DNA molecule that they recognize. The diagnostic significance of each of the two antibodies is different. The two types of antibodies will be discussed separately.
RNP ANTIBODIES
Of all the types of cellular RNA, autoantibodies in patients with CTD are directed to the small ribonucleoproteins (sRNP). This type constitutes the smallest portion of cellular RNA (<1% of the total RNA). sRNP consists of several molecules that contain RNA and an associated protein, thus the term ribonucleoprotein .26, 92 The protein component has enzymatic activity and plays a role in the processing of the RNA molecule.92 Antibodies to sRNP are directed against epitopes within the protein
OTHER AUTOANTIBODIES
Several other autoantibodies have been reported in patients with CTD. The diagnostic value of most of these antibodies is limited; only two are discussed in this review. Scl-70 antibodies are directed against the enzyme topoisomerase-I.138, 139, 140 This is a 100-kd basic protein that affects the tertiary structure of DNA molecules. Scl-70 antibodies are characteristic of SSc and help differentiate patients with extensive cutaneous and systemic involvement from those with limited disease.131,
FLUORESCENT ANA TEST
The fluorescent ANA test is a very good screening test for most of the previously discussed antibodies.
DIAGNOSTIC VALUE OF THE FLUORESCENT ANA TEST
There are several parameters that indicate the value of a certain test. These include sensitivity, specificity, positive predictive value, negative predictive value, and marginal benefit. Sensitivity refers to the probability of a test to have a positive result in a patient with the disease (true positives ÷ [true positives + false negatives]).12 Specificity refers to the probability of a test to have a negative result in a person without disease (true negatives ÷ [true negatives + false
RECENT SCREENING ANA TESTS
In the past few years, attempts have been made to replace the fluorescent ANA test with ELISA screening tests. There have been many ELISAs that have been reported to be of value for screening ANA tests. Some of these ELISAs utilize extracts of tissue containing various nuclear components. Other ELISAs utilize molecules synthesized by recombinant technology. Some ELISAs utilize individual recombinant molecules such as Ro(SS-A), whereas others utilize combinations of various molecules to increase
SEROLOGIC PROFILES IN CTDS
Each CTD has a rather specific autoantibody profile (Fig 1). Some of these profiles are “simple” in that they include one characteristic antibody (eg, anticentromere antibodies in patients with CREST5, 28, 29, 170, 171 and anti-U1RNP antibodies in patients with MCTD15, 23, 24, 25, 127). On the other hand, patients with SLE have a larger array of autoantibodies. Some of these antibodies are highly character-istic for SLE (nDNA antibodies1, 4, 49, 51, 172 and Sm antibodies15, 16, 104, 107, 134),
ANTIPHOSPHOLIPID ANTIBODIES
Antiphospholipid antibodies (APAs) are directed against negatively charged phospholipids, present in cell membranes.58, 173, 174, 175, 176, 177
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2012, Hospital Medicine ClinicsCitation Excerpt :The ANA test should not be used for general screening or indiscriminately. The ANA may be less useful in the elderly and in patients with chronic infections or malignancies.7,21 Tags: low predictive value ANA.
The lichenoid reaction pattern ('interface dermatitis')
2009, Weedon's Skin Pathology: Third EditionCutaneous histopathology of lupus erythematosus
2009, Diagnostic HistopathologyCitation Excerpt :The significance of seropositivity for antibodies to the cellular antigens depends upon the total quantity of antibody present, as indicated by the titre and nature of the assay used, as well as by the specificity of the antibody. With respect to the former, most reference commercial laboratories employ enzyme-linked immunosorbent assay (ELISA) technology, which is more sensitive, but less specific, than the older immunodiffusion methodologies.95 The nature of the antigen specificity as it relates to specific diagnostic categories of connective tissue disease is represented in Table 4.
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Reprint requests: Diya F. Mutasim, MD, Professor and Chairman, Department of Dermatology, University of Cincinnati, PO Box 670592, Cincinnati, OH 45267-0592. E-mail: [email protected].
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