Anti-nuclear antibodiesSignificance and limitations of test

By Hatem H. EleishiConsultant Rheumatologist

In this mini-lecture:

What are ANAs

How useful they are

How unuseful they can be

Conclusion

What are antinuclear antibodies?

Antibodies to nuclear proteins

What are nuclear proteins?

Proteins that have been synthesized in the nucleus and thereafter where distributed to their respective sites in the cell Nucleosomes

Ro

La

Smith

RNP

Jo-1

Scl-70

Ro

dsDNA

Nucleolar proteins

Ro

La

Smith

RNP

Jo-1

Scl-70

Ro

Nucleolar

dsDNA

Rim

Speckled

Homogenous Nucleosomes

Ro

La

Smith

RNP

Jo-1

Scl-70

Ro

dsDNA

Nucleolar proteins

Importance of ANAs

One: Serologic hallmarks of patients with systemic autoimmune disease (ANA diseases).

Serologic hallmarks of patients with systemic autoimmune disease: • SLE – sensitivity, 99 percent • Scleroderma – 97 percent • Mixed connective tissue disease – 93 percent • Polymyositis/dermatomyositis – 61 percent • Rheumatoid arthritis – 52 percent • Rheumatoid vasculitis – 33 percent • Sjögren's syndrome – 90 percent • Drug-induced lupus –100 percent • Discoid lupus – 15 percent • Pauciarticular juvenile chronic arthritis – 71 percent

TwoCan provide further diagnostic and prognostic data concerning patients who have minimal symptoms or who have clinical features of more than one autoimmune disease.

Examples

A young female with: PolyarthralgiasFatigueMalar rashPositive ANA

A lupus patient with: Anti-Ro antibodies

Limitations of utility and reliability

of ANA in diagnosis

of systemic autoimmune diseases

One:Can also be found in association with: Many autoimmune disorders that are not

defined by these antibodies

In certain infections and other disorders

In patients receiving certain drugs too.

Autoimmune disorders that are not defined by these antibodies: Hashimoto's thyroiditis – 46 percentGraves' disease – 50 percentAutoimmune hepatitis – 71 percentPrimary autoimmune cholangitis – 100 percentPrimary pulmonary hypertension – 40 percent

Chronic infectious diseases:MononucleosisSubacute bacterial endocarditisTuberculosisOther disorders: Some lymphoproliferative diseases.

In up to 50 percent of patients taking certain drugs; however, most of these patients do not develop drug-induced lupus.

Two: Their presence does not mandate the

presence of illness, since they can also be found in otherwise normal individuals.

False positive ANAs (ie, ANAs in the absence of autoimmune disease or known antigenic stimuli) are more commonly seen in women and in elderly patients. They are invariably in low titer.

Three: Accurate interpretation of different nuclear patterns is confounded several difficulties as: • The recognition of specific patterns is operator-dependent, and does not produce a permanent record. The fluorescence fades in one to two days, so that one cannot compare a result with other samples without photographing each test result.• One nuclear pattern may obscure and prevent the recognition of another pattern if several antibodies are present simultaneously.

As a result,

A positive ANA, although useful and important, yet should be interpreted with caution and within the appropriate clinical setting

As a result,

A good history compounded with a thorough clinical examination remain to be the mainstay of diagnosis

Thank you