Read The Lupus Book: A Guide for Patients and Their Families, Third Edition Online
Authors: Daniel J. Wallace
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.
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
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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
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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.
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Glossary