The Lupus Book: A Guide for Patients and Their Families, Third Edition (50 page)

3E 10 monoclonal antibody (ran out of funding), Biogen anti-CD40-L (effective but caused blood clots).

Biologics currently being evaluated for lupus:

CTLA-4Ig

interferes with T cell signaling

ETI-104

improves clearance of immune complexes

anti-IL 10

blocks a cytokine which promotes inflammation

anti-CD 22

monoclonal antibody which may help nephritis

Lymphostat B

antibody to BlyS, or B lymphocyte stimulation

LJP 1082

antibody to beta-2 glycoprotein which promotes blood clots

LJP 394

an anti-anti-DNA which improves lupus nephritis

Rituximab

lumphoma drug promising for serious lupus

Anti C5a

blocks complement mediated inflammation

Many other biologics are in development and undergoing animal testing using

other approaches such as inhibiting cytokines, peptide vaccinations, preparations which promote immune tolerance and blocking adhesion molecules which enhance inflammation.

WHAT ABOUT IMMUNE ABLATIVE AND

STEM CELL THERAPIES?

Giving the body a new immune system has been an attractive option for doctors

treating seriously ill lupus patients. In the mid-1990s, several centers began

studying stem cell transplantation in SLE. This aggressive approach usually

targets patients who severe, active, organ-threatening disease and have failed

corticosteroid and cyclophosphamide treatments. After obtaining a patient’s stem cells (cells made by the bone marrow with a capacity to make any type of cell)

with a specially equipped apheresis machine, individuals are given a very high

dose of cyclophosphamide (13G as opposed to the 1G usually given). At this

point, their stem cells, which have been grown to large amounts in tissue culture, are given back to the patient. The old bone marrow no longer has any memory

to promote an autoimmune reaction. Stem cell transplantion is expensive and

risky. Patients are prone to infections, need medicines which stimulate red cell, white cell or platelet production, evolve graft-versus-host reactions, and can have disease recurrence. A review of 100 patients who underwent the procedure

through 2003 internationally suggests that about 20 percent succumb or do not

respond, and the remainder have some response. It is too early to tell how these patients will do over the next few years.

Michelle Petri’s group at Johns Hopkins has pioneered
immune ablative ther-

apy
for serious lupus. This involves giving the patients 13 G of cyclophospham-

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The Management of Lupus Erythematosus

ide as discussed in the above paragraph but without stem cell transplantation.

At 5 years of follow up, 75 percent of patients were in a complete remission

on no or minimal medication. This is also an expensive, toxic procedure which

requires hospitalization and close monitoring, but is less involved than stem cell transplantation. A multicenter, independent evaluation of this method with

longer follow-up periods is needed.

Looking Beyond the Next Few Years

Lupus is characterized by “dyslexic T cells,” which lead to alterations in immune trafficking. In addition to the biologics being studied, several other investiga-tional lines are under scrutiny. These include antibodies or blockers of an array of cytokines, agents which block adhesion molecules (the cellular glue that attracts inflammatory factors to cells from blood. A class of medicines which

“tolerize” the body and prevent us from making antibodies to ourselves is being studied. Additional approaches include small molecules (peptides), antibodies

against antigen binding sites (anti-idiotypic antibodies), and T cell receptors.

Special vaccines with specifically designed payloads can not only alter immunity as we know it but also create new immune environments.

Albert Einstein said that God does not play dice with the universe. Some

astounding developments now support this philosophical remark. The concept

of apoptosis, or programmed cell death, has taken center stage in the last few

years. A variety of apoptosis genes sometimes seem to work at cross purposes,

but the bottom line is that cells which are damaged and should die fail to do so in lupus. The persistence of cellular debris or altered cells promotes the production of autoantibodies, perpetuating autoimmunity. Is lupus related to some

grand design?

Down the line, we will be able to fashion new immune environments which

may eliminate lupus. Not only will people who carry lupus genes be vaccinated

to prevent their activation, but gene therapies, or placing messages into cells to produce or not produce proteins, will become important. Improved new ways

of performing stem cell or bone marrow transplantation are theoretically capable of giving us an entirely new immune system programmed not to allow lupus to

exist or become active. These are indeed exciting times for a lupologist!

Our concepts of cell immunology change every year. Some ethicists and phi-

losophers in our discipline postulate that a higher authority created an immu-

notheology that can be manipulated only with rigid discipline if it is to be of any help to patients. We may hope that, by the year 2020, some lupus can be

prevented, no one will die from it, and treatment will be both effective and safe.

Glossary

ACR

The American College of Rheumatology. A professional association of

4000 American rheumatologists of whom 2800 are board-certified. Cri-

teria, or definitions for many rheumatic diseases, are called the ACR cri-

teria. Formerly known as the ARA (American Rheumatism Association).

Acute

Of short duration and coming on suddenly.

Adenopathy

A swelling of lymph nodes.

Adrenal glands

Small organs, located above the kidney, that produce many

hormones, including corticosteroids and epinephrine.

Albumin

A protein that circulates in the blood and carries materials to cells.

Albuminuria

A protein in urine.

Alopecia

Hair loss.

Analgesic

A drug that alleviates pain.

Anemia

A condition resulting from low red blood cell counts.

Antibodies

Special protein substances made by the body’s white cells for de-

fense against bacteria and other foreign substances.

Anticentromere antibody

Antibodies to a part of the cell’s nucleus; associ-

ated with a form of scleroderma called CREST (see its listing).

Anticardiolipin antibody

An antiphospholipid antibody.

Anti-double-stranded DNA (anti-DNA)

Antibodies to DNA; seen in half of

those with systemic lupus and implies serious disease.

Anti-ENA

Old term for extractable nuclear antibodies, which largely consist

of anti-Sm and anti-RNP antibodies.

Antigen

A substance that stimulates antibody formation; in lupus, this can be

a foreign substance or a product of the patient’s own body.

Anti-inflammatory

An agent that counteracts or suppresses inflammation.

Antimalarials

Drugs originally used to treat malaria that are helpful for lupus.

Antinuclear antibodies (ANA)

Proteins in the blood that react with the nuclei

of cells. Seen in 96 percent of those with SLE, in 5 percent of healthy

individuals, and in most patients with autoimmune diseases.

Antiphospholipid antibody

Antibodies to a constituent of cell membranes

[268]

Glossary

seen in one-third of those with SLE. In the presence of a co-factor, these

antibodies can alter clotting and lead to strokes, blood clots, miscarriages,

and low platelet counts. Also detected as the lupus anticoagulant.

Anti-RNP

Antibody to ribonucleoprotein. Seen in SLE and mixed connective

tissue disease.

Anti-Sm

Anti-Smith antibody; found only in lupus.

Anti-SSA
,

or the Ro antibody, is associated with Sjo¨gren’s syndrome, sun

sensitivity, neonatal lupus, and congenital heart block.

Anti-SSB,

or the La antibody, is almost always seen with anti-SSA.

Apheresis

See Plasmapheresis.

Apoptosis

Programmed cell death.

Artery

A blood vessel that transports blood from the heart to the tissues.

Arthralgia

Pain in a joint.

Arthritis

Inflammation of a joint.

Ascites

An abnormal collection of abdominal fluid.

Aspirin

An anti-inflammatory drug with pain-killing properties.

Atrophy

A thinning of the surface; a form of wasting.

Autoantibody

An antibody to one’s own tissues or cells.

Autoimmunity

Allergy to one’s own tissues.

Autoimmune hemolytic anemia

See hemolytic anemia.

B lymphocyte or B cell

A white blood cell that makes antibodies.

Biopsy

Removal of a bit of tissue for examination under the microscope.

Bursa

A sac of synovial fluid between tendons, muscles, and bones that pro-

motes easier movement.

Butterfly rash

Reddish facial eruption over the bridge of the nose and cheeks,

resembling a butterfly in flight.

Capillaries

Small blood vessels connecting the arteries and veins.

Cartilage

Tissue material covering bone. The nose, outer ears, and trachea

consist primarily of cartilage.

Candida

A yeast.

Chronic

Persisting over a long period of time.

CNS

Central nervous system.

Collagen

Structural protein found in bone, cartilage, and skin.

Collagen vascular disease (also called connective tissue disease)

Antibody-

mediated inflammatory process of the connective tissues, especially the

joints, skin, and muscle.

Congenital heart block

Dysfunction of the rate/rhythm conduction system in

the fetal or infant heart.

Connective tissue

The ‘‘glue’’ that holds muscles, skin, and joints together.

Complement

A group of proteins that, when activated, promote and are con-

sumed during inflammation.

Glossary

[269]

Complete blood count (CBC)

A blood test that measures the amount of red

blood cells, white blood cells, and platelets in the body.

Corticosteroid

Any natural anti-inflammatory hormone made by the adrenal

cortex; also can be made synthetically.

Cortisone

A synthetic corticosteroid.

Creatinine

A blood test that measures kidney function.

Creatinine clearance

A 24-hour urine collection that measures kidney func-

tion.

CREST syndrome

A form of limited scleroderma characterized by C (calcium

deposits under the skin), R (Raynaud’s phenomenon), E (esophageal dys-

function), S (sclerodactyly or tight skin), and T (a rash called telangiec-

tasia).

Crossover syndrome

An autoimmune process that has features of more than

one rheumatic disease (e.g., lupus and scleroderma).

Cryoglobulins

Protein complexes circulating in the blood that are precipitated

by cold.

Cutaneous

Relating to the skin.

Cytokine

A group of chemicals that signal cells to perform certain actions.

Dermatologist

A physician specializing in skin diseases.

Dermatomyositis

An autoimmune process directed against muscles associated

with skin rashes.

Discoid lupus

A thick, plaquelike rash seen in 20 percent of those with SLE.

If the patient has the rash but not SLE, he or she is said to have
cutaneous
(discoid) lupus erythematosus.

Diuretics

Medications that increase the body’s ability to rid itself of fluids.

DNA

Deoxyribonucleic acid. The body’s building blocks. A molecule respon-

sible for the production of all the body’s proteins.

Dysphagia

Difficulty in swallowing.

Ecchymosis

Purplish patch caused by oozing of blood into the skin.

Edema

Swelling caused by retention of fluid.

ELISA
(enzyme-linked immunosorbent assay)

A very sensitive blood test for

detecting the presence of autoantibodies.

Enzyme

A protein that accelerates chemical reactions.

Erythema

A reddish hue.

Erythematous

Having a reddish hue.

Estrogen

Female hormone produced by the ovaries.

Exacerbations

Symptoms reappear; a flare.

False-positive serologic test for syphilis

A blood test revealing an antibody

that may be found in patients with syphilis and that gives false-positive

results in 15 percent of patients with SLE. Associated with the lupus

anticoagulant and antiphospholipid antibodies.

[270]

Glossary