Autoantibodies as Diagnostic Markers

Cure Arthritis Naturally

Cure Arthritis Naturally

Get Instant Access

The diseases associated with autoantibodies can be divided into two broad groups: the organ-specific autoimmune diseases, in which autoantibodies have the ability to react with autoantigens from a particular organ or tissue, and the multi-system autoimmune diseases, in which autoantibodies react with common cellular components that appear to bear little relevance to the underlying clinical picture. In both cases particular autoantibody specificities can serve as diagnostic markers (Table 1.1). A synopsis of the methodology used to determine the presence of autoantibodies, including high-throughput multiplex assays, is covered by Rufus Burlingame and Carol Peebles in Chapter 8. Discussion of more specialized assay systems using synthetic peptides to detect autoantibodies is covered by Jean-Paul Briand and Sylviane Muller in Chapter 9.

In the multi-system autoimmune diseases, there are several features of the relationship between autoantibody specificity and diagnostic significance that bear consideration. Autoantigens in these diseases are components of macromolecu-lar structures such as the nucleosome of chromatin and the small nuclear ribo-nucleoprotein (snRNP) particles of the spliceosome, among others. Autoanti-bodies to different components of the same macromolecular complex can be diagnostic for different clinical disorders [35, 36]. Thus, the core proteins B, B', D, and E, which are components of the U1, U2, and U4-U6 snRNPs and are antigenic targets in the anti-Smith antigen (Sm) response in SLE, are different from the U1 snRNP-specific proteins of 70 kDa, A and C, which are targets of the anti-nRNP response in mixed connective tissue disease (MCTD; see Table 1.1). It has also been observed that certain autoantibody responses are consistently associated with one another. The anti-Sm response, which is diagnostic of SLE, is commonly associated with the anti-nRNP response; but the anti-nRNP response can occur without the anti-Sm response, in which case it can be diagnostic of MCTD. These two observations suggest that the snRNP complexes responsible for the autoantibody response against the spliceosome in MCTD may differ from the snRNP complexes that produce the anti-spliceosome response in SLE. Other autoantibody responses demonstrate similar associations and restrictions. The anti-SS-A/Ro response (see Table 1.1) frequently occurs alone in SLE, but the anti-SS-B/La response in Sjogren's syndrome is almost always associated with the anti-SS-A/Ro response. Similarly, the anti-chromatin response occurs alone in drug-induced lupus [37] but is usually associated with the anti-dsDNA response in idiopathic SLE [38].

Autoantibody specificities may occur at different frequencies in a variety of diseases, and the resultant profile consisting of distinct groups of autoantibodies in different diseases can have diagnostic use [35]. In some cases the grouping of autoantibody specificities, such as the preponderance of anti-nucleolar auto-antibodies in scleroderma (Table 1.1) [39], provides provocative but poorly understood relationships with clinical diagnosis. Unlike SLE, where a single patient may have multiple autoantibody specificities to a number of unrelated nuclear

Table 1.1 Examples of clinical diagnostic specificity of autoantibodies.

Autoantibody specificitya

Molecular specificity

Clinical association

Organ-specific autoimmune diseases

Anti-acetylcholine receptor* Anti-TSH receptor* Anti-thyroglobulin* Anti-thyroid peroxidase* Anti-mitochondria*

Anti-keratinocyte* Anti-keratinocyte* Anti-GAD65

Acetylcholine receptor TSH receptor Thyroglobulin Thyroid peroxidase Pyruvate dehydrogenase complex

Desmoplakin I homologue Desmoglein

Glutamic acid decarboxylase, 65 kDa

Myasthenia gravis Graves' disease Chronic thyroiditis Chronic thyroiditis Primary biliary cirrhosis

Bullous pemphigoid Pemphigus foliaceus Type 1 diabetes

Multi-system autoimmune diseases

Anti-double-stranded DNA* Anti-Sm*

Anti-nRNP

Anti-SS-A/Ro

Anti-SS-B/La

Anti-Jo-1* Anti-fibrillarin*

Anti-RNA polymerase 1*

Anti-DNA topoisomerase 1

Anti-centromere*

cANCA Anti-CCP*

B form of DNA

U2, and U4-U6 snRNP

70-kDa A and C proteins of U1-snRNP

60- and 52-kDa proteins associated with hY1-Y5 RNP

complex

47-kDa phosphoprotein complexed with RNA polymerase III transcripts Histidyl tRNA synthetase 34-kDa protein of C/D box-containing snoRNP (U3, U8, etc.)

Subunits of RNA polymerase 1 complex

100-kDa DNA topoisomerase I

Centromeric proteins CENP-A, -B, and -C

Serine proteinase (proteinase 3) Cyclic citrullinated peptide

SLE SLE

MCTD, SLE

SS, neonatal lupus, SLE SS, neonatal lupus, SLE

Polymyositis Scleroderma

Scleroderma

Scleroderma

CREST (limited scleroderma)

Wegener's vasculitis Rheumatoid arthritis a) Disease-specific diagnostic marker antibodies indicated by asterisk.

Abbreviations: SLE = systemic lupus erythematosus; MCTD = mixed connective tissue disease; SS = Sjögren's syndrome; cANCA = cytoplasmic anti-neutrophil cytoplasmic antibody; TSH = thyroid-stimulating hormone; CREST = calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia.

autoantigens (e.g., DNA, Sm, SS-A/Ro), scleroderma patients infrequently have multiple autoantibody specificities to nucleolar autoantigens that are unrelated at the macromolecular level (i.e., not part of the same macromolecular complex).

In planning the content of this book, it was decided that it was not possible to devote multiple chapters to discussion of disease-specific autoantibodies. Instead, a single chapter has been assigned to the two major forms of autoimmune disease (i.e., organ-specific and systemic), and two additional chapters have been allocated to cover the major diseases within each group. Karsten Conrad and Michael Bachmann have outlined autoantibodies and systemic autoimmune diseases (Chapter 10), while Falk Heipe has expanded upon autoantibodies in systemic lupus erythematosus (Chapter 11) and Tsuneyo Mimori has focused on autoantibodies in rheumatoid arthritis (Chapter 12). In the organ-specific disease section, Michael Manns and colleagues expand the discussion on autoantibodies and organ-specific autoimmunity (Chapter 13) by including comments on autoimmune liver diseases. Osvaldo Martines and Bellur Prabhakar provide an excellent analysis of autoantibodies in autoimmune thyroid disease (Chapter 14) including comments on functionally relevant epitopes. See Chapters 2 and 20 for more on this topic. Another excellent chapter on organ specific autoimmunity is that by Sarah Weenink and Michael Christie on autoantibodies in diabetes (Chapter 15). The material on T-cell responses in this chapter can be expanded upon by reading Chapters 19 and 21.

Was this article helpful?

0 0
Arthritis Joint Pain

Arthritis Joint Pain

Arthritis is a general term which is commonly associated with a number of painful conditions affecting the joints and bones. The term arthritis literally translates to joint inflammation.

Get My Free Ebook


Post a comment