Unit 3 autoimmunity part 2 systemic lupus erythematosus part 3 rheumatoid arthritis
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Unit 3 Autoimmunity Part 2 Systemic Lupus Erythematosus Part 3 Rheumatoid Arthritis. Terry Kotrla, MS, MT(ASCP)BB. Expectation. Students are expected to know: Signs and symptoms, especially part of body affected Age and sex if appropriate Tests to diagnose Treatment.

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Unit 3 Autoimmunity Part 2 Systemic Lupus Erythematosus Part 3 Rheumatoid Arthritis

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Unit 3 autoimmunity part 2 systemic lupus erythematosus part 3 rheumatoid arthritis

Unit 3 AutoimmunityPart 2 Systemic Lupus ErythematosusPart 3 Rheumatoid Arthritis

Terry Kotrla, MS, MT(ASCP)BB



  • Students are expected to know:

    • Signs and symptoms, especially part of body affected

    • Age and sex if appropriate

    • Tests to diagnose

    • Treatment

Systemic lupus erythematosus

Systemic Lupus Erythematosus

  • Chronic, systemic inflammatory disease caused by immune complex formation.

  • The word "systemic" means the disease can affect many parts of the body.

  • Pathophysiology associated with clinical features secondary to immune complexes depositing in tissues resulting in inflammation.

  • Parts of the body affected include: the joints, skin, kidneys, heart, lungs, blood vessels, and brain.

Systemic lupus erythematosus1

Systemic Lupus Erythematosus

  • Peak age of onset is 20 to 40 years of age.

  • Found more frequently in women.

  • Has both genetic and environmental factors.

  • Often difficult to diagnose.

  • “Great imitator” as it mimics or is mistaken for other illnesses.

  • Can be fatal but survival rates increasing.

Sle clinical signs

SLE Clinical Signs

  • Extremely diverse and nonspecific.

  • Joint involvement most frequent signs are polyarthralgia and arthritis which occur in 90% of patients.

  • Skin manifestations next most common.

  • Erythematosus rash may appear.

  • Most classic is butterfly rash.

Symptoms of sle

Symptoms of SLE

Sle butterfly rash

SLE Butterfly Rash

  • The source of the name "lupus" is unclear. All explanations originate with the characteristic butterfly-shaped malar rash that the disease classically exhibits across the nose and cheeks.

  • Various accounts, some doctors thought the rash resembled a wolf pattern. In other accounts doctors thought that the rash, which was often more severe in earlier centuries, created lesions that resembled wolf bites or scratches.

  • Stranger still, is the account that the term "Lupus" didn't come from latin at all, but from the term for a French style of mask which women reportedly wore to conceal the rash on their faces

Sle clinical signs1

SLE Clinical Signs

  • Renal involvement very common.

    • Caused by deposition of immune complexes in kidney tissue.

    • Leads to renal failure, most common cause of death.

  • Other systemic effects:

    • Cardiac

    • Central nervous system

    • Liver

    • Hematologic abnormalities

Immunologic findings

Immunologic Findings

  • Lupus Erythematosus (LE) cell, neutrophil which has engulfed the antibody-coated nucleus of another cell.

    • First classic test to aid in diagnosis.

    • Not utilized anymore, may still see in older references.

  • Over activity of B cells main immunologic characteristic.

    • Antinuclear antibodies produced.

    • More than 28 antibodies associated with LE have been identified.

    • Level of antibody production correlates with severity of symptoms.

    • Estrogen enhance B cell activation.

Le cell

LE Cell

  • "LE cell" test which has value only in demonstrating how the concept of autoantibodies work.

  • Pink blobs are denatured nuclei.

  • Two in this slid, one being phagocytosed in the center by a PMN.

  • This test is not nearly as sensitive as the ANA which has supplanted the LE cell test. Therefore, NEVER order an LE cell test. [Image contributed by Elizabeth Hammond, MD, University of Utah]

Immunologic findings1

Immunologic Findings

  • Decrease in absolute number of T cells

  • Accumulation of immune complexes with activation of complement lead to kidney damage.

  • Drug induced lupus may occur, discontinue drug, symptoms usually disappear.

Laboratory diagnosis

Laboratory Diagnosis

  • Screening test for anti-nuclear antibodies (ANA) first test done.

  • Antibodies directed against nuclear material of cells.

  • Flourescent anti-nuclear antibody (FANA) most widely used, extremely sensitive, low diagnostic specificity.

    • Animal or human cells fixed to slide.

    • Add patient serum and incubate.

    • Wash to remove unreacted antibody.

    • Add anti-human globulin labeled with fluorescent tag or enzyme.

Antinuclear antibody test

Antinuclear Antibody Test

  • Antinuclear antibodies (ANA) are autoantibodies against various cell nucleus antigens and are found in patients with autoimmune diseases such as SLE.

  • Some of ANA are considered to be useful for diagnosis of autoimmune diseases.

  • This picture illustrates the most common antigens used in the ANA

  • At the MLT level you will not be required to memorize.

Unit 3 autoimmunity part 2 systemic lupus erythematosus part 3 rheumatoid arthritis


  • Patients antinuclear antibody titer of 1:40 and characteristic multiorgan system involvement can be diagnosed with SLE without additional testing

  • Patients with antibody titer of 1:40 who fail to meet full clinical criteria should undergo additional testing including:

    • Tests for antibody to doublestranded DNA antigen

    • Antibody to Sm nuclear antigen.

  • Antinuclear antibody titer of less than 1:40 usually rules out systemic lupus erythematosus but patients with persistent, characteristic multisystem involvement may be evaluated for possible antinuclear antibody–negative disease.

Unit 3 autoimmunity part 2 systemic lupus erythematosus part 3 rheumatoid arthritis


  • Patterns of reactivity:

    • Homogenous-entire nucleus stained

    • Peripheral-rim of nucleus stained

    • Speckled-spots of stain throughout nucleus

    • Nucleolar-nucleolus only stained

  • False positives and negatives occur.

  • If positive, perform profile testing.

Unit 3 autoimmunity part 2 systemic lupus erythematosus part 3 rheumatoid arthritis


  • For the next exam you must be able to:

    • Name the 4 primary reactions

    • Describe the 4 primary reactions seen

    • Identify the type of reaction in a photo

Homogeneous pattern

Homogeneous Pattern

  • Smooth, even staining of the nucleus with or without apparent    masking of the nucleoli



  • 23 or 46 (or some multiple of 46) bright speckles or ovoid granules spread over the nucleus of interphase cells



  • Fluorescence is most intense at the periphery of the nucleus with a large ring starting from the internal nuclear membrane and the rest of the nucleus showing weaker yet smooth staining.



  • Large speckles covering the whole nucleoplasm, interconnected by a fine fluorescent network.

Anti nuclear antibodies detected by fana

Anti-nuclear antibodies detected by FANA

  • Double-stranded DNA (ds-DNA) antibodies are most specific for SLE, correlate well with disease activity.

  • Antihistone antibody second major antibody found in SLE.

  • Deoxyribonucleoprotein (DNP) antibody, responsible for LE cell phenomena and available as a latex agglutination test.

  • Anti-Sm antibody, specific for LE.

  • SS-A/Ro and SS-B/La antibodies, most common in patients with cutaneous manifestations.

  • Anti-nRNP detected in patients with SLE as well as mixed connective tissue disease.

  • Presence of antibodies not diagnostic, may be present due to other diseases.

Anti nuclear antibody by immunodiffusion

Anti-Nuclear Antibody by Immunodiffusion

  • Used to determine specificity.

  • Ouchterlony double diffusion most frequently used to identify antibodies to: Sm, nRNP, SS-A/Ro, SS-B/La and others.

  • Test is not as sensitive but very specific.

Systemic lupus erythematosus2

Systemic Lupus Erythematosus

Extractable nuclear antigen

Extractable Nuclear Antigen

  • Antibody to cytoplasmic and nuclear components.

  • Over 100 different antigens described.

  • It is associated with mixed connective disease and SLE with particular features (arthritis, myositis, Raynaud's phenomenon - also association with HLA-DR4 and HLA-DQw8).

Extractable nuclear antigen ena

Extractable Nuclear Antigen ENA

Antiphospholipid antibodies

Antiphospholipid Antibodies

  • Antiphospholipid antibodies may be present and are of two types.

    • Anticardiolipin.

    • Lupus anticoagulant, if present, may cause spontaneous abortion and increase

  • Risk of clotting, platelet function may be affected.



  • Aspirin and anti-inflammatories for fever and arthritis.

  • Skin manifestations-anti-malarials or topical steroids.

  • Systemic corticosteroids for acute fulminant lupus, lupus nephritis or central nervous system complications.

  • Five year survival rate is 80 to 90%.

Rheumatoid arthritis

Rheumatoid Arthritis

  • Chronic systemic inflammatory disease primarily affecting the joints, but can affect heart, lung and blood vessels.

  • Women three more times as likely as men to have it.

  • Typically strikes at ages between 20 and 40, but can occur at any age.

  • The three major symptoms of arthritis are joint pain, inflammation, and stiffness.

  • Progress of disease varies.



  • Group of conditions involving damage to the joints of the body.

  • Over 100 different forms of arthritis.

  • Will discuss the autoimmune type, rheumatoid arthritis.

Clinical signs

Clinical Signs

  • Diagnosis based on criteria established by American College of Rheumatologists, must have at least 4 of the following:

    • Morning stiffness lasting 1 hour.

    • Swelling of soft tissue around 3 or more joints.

    • Swelling of hand/wrist joints.

    • Symmetric arthritis.

    • Subcutaneous nodules

    • Positive test for rheumatoid factor.

    • Xray evidence of joint erosion.

Clinical signs1

Clinical Signs

  • Symptoms initially non-specific: malaise, fever, weight loss, and transient joint pain.

    • Morning stiffness and joint pain improve during the day.

    • Symmetric joint pain: knees, hips, elbows, shoulders.

    • Joint pain leads to muscle spasm, limits range of motion, results in deformity.

  • Approximately 25% of patients have nodules over bones (necrotic areas), nodules can also be found in organs.

  • Certain bacteria may trigger RA due to certain proteins that possess antigens similar to those antigens found in joint, ie, molecular mimicry

Immunologic findings2

Immunologic Findings

  • Rheumatoid Factor (RF) is an IgM antibody directed against the Fc portion of the IgG molecule, it is an anti-antibody.

  • Not specific for RA, found in other diseases.

  • Immune complexes form and activate complement and the inflammatory response.

  • Enzymatic destruction of cartilage is followed by abnormal growth of synovial cells, results in the formation of a pannus layer.

Rheumatoid arthritis1

Rheumatoid Arthritis

Rheumatoid arthritis2

Rheumatoid Arthritis



  • Diagnosis is based on:

    • Clinical findings.

    • Radiographic findings

    • Laboratory testing.

Laboratory testing

Laboratory Testing

  • Rheumatoid Factor

    • IgM autoantibody directed against the Fc portion of the antibody molecule.

    • Detected by testing patient serum with red blood cells or latex particles coated with IgG, agglutination is a positive result.

  • Nephelometry and ELISA techniques are available to quantitate the RF.

  • Erythrocyte Sedimentation Rate (ESR) used to monitor inflammation.

  • C-Reactive protein (CRP) is utilized to monitor inflammation



  • Goal to achieve lowest level of disease, remission if possible, minimization of joint damage.

  • Rest and non-steroidal anti-inflammatory drugs control swelling and pain.

  • Substantial functional loss seen in 50% of patients within 5 years.

  • Slow acting anti-rheumatic drugs are coming into use but have side affects.

  • Joint replacement.

The end

The End

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