Autoantibodies as Predictors Early Markers of Disease

Most AIDs are characterized by a subclinical prodrome, during which the only evidence of the developing disorder may be the manifestation of disease-specific autoimmunity. Indeed, AABs that are typically produced in defined disease manifestations are detectable months to years before appearance of the respective clinical symptoms [15-26]. This has been shown for SLE-, RA-, SSc-, SjS-, and PM-typical AABs by retrospective (use of stored sera) and prospective (follow-up) studies (Table 10.2). Therefore, certain AABs might predict disease development in risk groups or even in the general population. The prediction of AIDs becomes more and more important as effective novel immune intervention therapies become available. Recently, the most important clinical utility of AAB testing has been diagnosis of the respective AIDs as early as possible or diagnosis of limited or non-typical forms of the disease (for examples, see Section 10.3.4.1).

Table 10.2 Autoantibodies as early indicators of the development of systemic autoimmune diseases.

Autoantibodies directed against

Diseases

Retrospective (R) or prospective (P) studies

Ref.

Cyclic-citrullinated

Rheumatoid

R: analysis of stored sera from blood donors

19, 20

peptides (CCP)

arthritis (RA)

who developed RA showed that anti-CCP

antibodies predate RA by several years

(mean 4.5 years; range 0.1-13.8 years)

Double-stranded

Systemic lupus

R: testing of stored sera from US Armed

15

DNA (dsDNA)

erythematosus

Services Serum Repository from former

(SLE)

military personal who developed SLE showed

that anti-dsDNA antibodies may appear up to

9 years (mean: 2.2 years) before onset of SLE

Sm

SLE

R (see dsDNA): anti-Sm antibodies may

15

appear up to 8 years (mean: 1.5 years) before

onset of SLE

Ro/SS-A

SLE, Sjogren's

R (see dsDNA): anti-Ro/SS-A antibodies

15-17

syndrome

appeared as early as 10 years before the

(SjS)

first onset of disease (mean 3.6 years)

P: a 5-10-year follow-up of anti-Ro/SS-A-

positive asymptomatic women who gave birth

to babies with neonatal lupus showed that

approximately half of these persons developed

SLE, SjS, or undifferentiated syndromes

La/SS-B

SLE, SjS

R (see dsDNA): anti-La/SS-B antibodies may

15

appear up to 8 years (mean: 3.6 years) before

onset of SLE

Centromere

Systemic

P: patients with Raynaud's phenomenon

22-24,

proteins

sclerosis

(RP) initially positive for ACA or ATA had a

26

(CENP-B, ACA)

(SSc)

63-fold increased risk for developing signs of

CTD/SSc compared to the remaining patients

with RP

P: more than one-third of asymptomatic ACA-

positive uranium miners developed SSc mani

festations or definite SSc

DNA

Systemic

P: see ACA

23,

topoisomerase I

sclerosis

P: nearly one-third of asymptomatic ATA-posit-

24-26

(scl-70, ATA)

ive uranium miners developed SSc manifesta

tions or definite SSc

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