Page 1779 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1248 PART 11: Special Problems in Critical Care

■ ANTINUCLEAR ANTIBODIES methods. The test is now performed most commonly on HEp-2 cells

The presence of antinuclear antibodies (ANA) in high titer provides and is sensitive for detecting the presence of SLE and other collagen
vascular diseases, but as noted above, the test is hindered by the lack
presumptive evidence for the presence of systemic autoimmune dis-
eases, and in particular, SLE (Table 126-1). Lower levels of ANA can be of specificity. Interest in specific ANA has spawned a long and at times
confusing list of tests of variable utility. A brief overview of the most
51
nonspecific, possibly normal, and at times explained by age, prior drug
therapy or viral infection (especially parvovirus or Epstein-Barr virus), useful specific ANA tests follows.
or a first-degree relative with lupus. Low levels of ANA in the elderly can Anticentromere Antibody: This antibody to the kinetochore of chromo-
be particularly misleading in the presence of an age-related elevation of somes is detected by recognition of a particular pattern of immunofluo-
the ESR. It has been estimated that up to 25% to 30% of normal, healthy rescence on HEp-2 cells. It is, in general, the only pattern detected on
individuals will have a positive ANA (depending on the dilution or titer screening ANA useful for diagnostic purposes. The antibody is found
used as a cutoff). 49,50 These data are confounded by a small but definite most commonly in the limited cutaneous scleroderma. In this subset of
incidence of new cases of SLE among the elderly. Screening ANA is patients, the test has been positive in 44% to 98% of those tested. 52,53 Less
typically done by a standard, indirect immunofluorescence technique, commonly, it may be seen in diffuse scleroderma and primary biliary
although some laboratories are using solid-phase immunoenzymatic cirrhosis with or without evidence of scleroderma.
Antibodies to DNA: Antibodies to DNA fall into two major categories
by virtue of reacting to antigenic determinants on the phosphate deoxy-
TABLE 126-1 Serologic Tests in Rheumatic Diseases ribose backbone of the DNA helix or determinants on the nucleotide
Antibody Disorder bases. The former represent antibodies to native double-stranded DNA
while the latter react with single-stranded DNA. Antibodies to single-
a
Tests with higher specificity for systemic autoimmune disease:
stranded DNA are more common and are found across a spectrum of
Antinative DNA SLE rheumatic and nonrheumatic disorders. They are of no practical clinical
Anti-Sm (Smith) SLE utility. Antibodies to double-stranded DNA are useful since they have
high specificity for SLE and are found in 60% to 70% of patients with
Anti-Ro (SS-A) Congenital heart block
that disease. 54,55 In some, but not all lupus patients, levels of anti-DNA
Antinuclear antibody-negative lupus antibody (along with complement levels) will correlate positively with
Subacute cutaneous lupus disease activity, especially in the kidney. Low levels of this antibody have
been found rarely in other connective tissue diseases.
Primary Sjögren syndrome
SLE Antibodies to Sm: This antibody is named after a patient (“Smith”) in
whom it was first described. The antibody has high specificity for SLE
Anticentromere Limited cutaneous variant of scleroderma (CREST)
and is rarely found in patients with other connective tissue diseases.
Anti-Scl-70 (topoisomerase I) Diffuse scleroderma, less commonly limited scleroderma Sensitivity is only about 30% for SLE. Sm is not to be confused with an
Antineutrophil cytoplasmic GPA antibody to smooth muscle (SM), which is not a marker for collagen
antibody Microscopic polyangiitis vascular disease, but is found in patients with chronic liver disease.
There is no specific clinical profile of Sm-positive patients with SLE.
Idiopathic crescentic glomerulonephritis Titers are not useful for assessment of disease activity.
Anti-ribonucleoprotein SLE
Antibodies to nRNP: Antigenic determinants for nuclear ribonucleopro-
Mixed connective tissue disease tein (nRNP) may occur in a molecular complex with Sm, and antibodies
Undifferentiated connective tissue disease to Sm and RNP are often found in the same patient. Antibodies to nRNP
may be seen in SLE, scleroderma, or overlap syndromes. The presence of
Anti-La (SS-B) SLE
overlapping clinical features and high titers of antibody to RNP defines
Primary Sjögren syndrome a clinical subset of patients referred to as those with mixed connective
Tests with lower specificity for systemic autoimmune disease: tissue disease (MCTD).
Antinuclear antibody SLE Antibodies to SS-A/Ro and SS-B/La: These antigens were originally
Other autoimmune diseases described in patients with Sjogren syndrome (SS) and SLE. They are
RNA-protein conjugates. SS-A and Ro have antigenic identity, as do
Normals (usually low titer)
SS-B and La. The presence of SS-B/La may be seen in SLE or Sjogren
Drug-induced syndrome, and in most assays is measured along with SSA/Ro. The Ro
Aging antibody has been described in 60% of so-called ANA-negative SLE.
Rheumatoid factor Rheumatoid arthritis Anti-Ro antibody is also highly prevalent in the setting of neonatal
lupus with congenital heart block. In those cases, the antibody is found
Mixed cryoglobulinemia in mother and child. 56,57 Other clinical scenarios associated with anti-Ro
Aging antibody include subacute cutaneous lupus and C2 deficiency. Anti-Ro
Subacute bacterial endocarditis antibody occurs in 25% to 40% of unselected patients with SLE. The
major indications for ordering these tests are: in a setting in which
Any cause of chronic antigenic stimulation
SLE is strongly suspected but the screening ANA is negative, a patient
Anticardiolipin antibody Anticardiolipin antibody syndrome suspected of having Sjogren syndrome, congenital heart block, neonatal
Normals lupus, and the initial evaluation of a patient with a positive ANA.
Viral illness Antibodies to Scl-70 (Topoisomerase I): Antibodies to Scl-70 are directed
58
SLE toward DNA topoisomerase I and inhibit its function. They are
found in 20% to 40% of patients classified as diffuse systemic sclerosis,
Other autoimmune diseases
and less commonly in patients with limited cutaneous scleroderma.
GPA, granulomatous polyangiitis; SLE, systemic lupus erythematosus. Determination of this antibody is part of the evaluation of patients
a Unlikely to be found in normals, with aging, or as a nonspecific immune response to infection. suspected of having scleroderma.

section11.indd 1248 1/19/2015 10:52:16 AM