Positive Options for Living with Lupus (5 page)

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Chapter 3

The Causes of Lupus

While no one knows what causes lupus, promising clues are scat-tered all over the place, like wolf prints outside a lair. Almost certainly there is no single cause, though we are able to rule out some causes.

◗ It is not transmitted by any infectious agent such as a bac-terium, virus, or parasite. That means you can’t “catch”

lupus from another person, though infection may play some part in triggering it (more on this later).

◗ It is not caused by any known environmental agent such as industrial chemicals, toxic fumes, inhaled fibers (e.g., asbestos), microwaves, or radio towers—though, again, some environmental agent may play a part in triggering the disease or triggering a flare-up.

◗ It is not caused by a deficiency of any substance needed during crucial stages of embryo or infant development (e.g., vitamin, essential mineral, vital nutrient, hormone, or enzyme).

◗ It does not represent an allergic reaction or sensitivity to anything the patient (or the patient’s mother) has eaten or come in contact with—though, again, such factors may
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play a part in why some people develop lupus, and lupus sufferers are as likely to have allergies as anyone else.

◗ It is not caused by a gene, or genes, handed down from parent to child. This does not mean that there is nothing in lupus sufferers’ genetic inheritance that makes them more vulnerable to the disease.

Does it matter if we are unsure what causes lupus? Yes. You can treat an illness by using a mixture of experiment and observation, as ancient herbalists and witch doctors knew, but you cannot hope to cure, let alone prevent, it unless you can understand its underlying causes. As knowledge grows of what goes wrong in lupus—invariably a complex chain reaction involving more than a single bodily process—doctors have more opportunities to intervene, that is, to cut it off at the pass and ultimately stop it in its tracks.

So researchers are looking not for a single cause but for a combination of factors that lead to a person’s developing lupus.

A Genetic Predisposition?

Although lupus is not caused by a defective gene handed down from parent to child, there is certainly evidence that some genetic factor is at work. When lupus is diagnosed it is not uncommon to find that the patient has relatives who have had lupus, or at the very least have had lupus-like symptoms. What seems likely is that some genetic vulnerability to developing the disease is inherited. A child with lupus in the family may be born a lupus “sleeper,” with the vulnerability gene lying dormant until sparked into action by some trigger in the outside world.

Ginny’s Story

While Ginny was in her mid-tw enties, her husband, Bob, was posted to East Africa with the Air F orce. She went with him.

She had always been an outdoor person, and in Nairobi she was able to swim and ride and spend fr om dawn to dusk in the open. When she first noticed the rash on her face she thought POL text Q6 good.qxp 8/12/2006 7:39 PM Page 25

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she had gotten slightly sunburned, though she t anned easily and had never before been bothered by too much sun. She wore a hat and slathered on sunscreen, and the rash seemed to clear up. Then the aches and pains in her hands s tarted. She didn’t have the energy or inclination to go riding or to the swimming pool. The medical officer at the air force base murmured something about “ar thritis” and suggested aspirin. Ginny suffered silently indoors. In her w eekly phone call t o her mother she complained of her painful hands. Her mom said, “I think y ou could have lupus.” Ginny’s aunt had nearly died during her first pregnancy, she said, and had been diagnosed as ha ving lupus.

“Come to think of it, y ou used to complain of pains in y our hands and wrists after playing tennis when you were at school,”

said her mother. “We just put it down to growing pains.”

Remember the mention of growing pains. The topic crops up again in Chapter 4. Experienced rheumatologists have commented on how often growing pains are mentioned in the history of people who are diagnosed with lupus as adults.

Will My Baby Get It?

When a woman develops lupus she learns that she may have problems with pregnancy. After asking “Is it all right to have children?”

she will almost certainly ask, “Will my baby get lupus?” While there is a slightly increased chance of this—about 5 percent—at least the baby of a lupus mother is unlikely to develop lupus unnoticed. As explained, lupus belongs to the autoimmune family of diseases, and there is a great deal of overlap in how the immune system malfunc-tions and the symptoms that result from such diseases. Support for the idea that there is some inherited predisposition to developing autoimmune disease comes from several sources. First, the relatives of those with autoimmune conditions are more likely to have the same or a similar condition. About 20 percent of lupus sufferers have first-degree relatives—parents, children, or siblings—who have either lupus or some other autoimmune condition like insulin-dependent (type 1) diabetes or rheumatoid arthritis. What’s more, POL text Q6 good.qxp 8/12/2006 7:39 PM Page 26

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if the blood of a lupus sufferer’s healthy close relatives is tested, an additional 20 percent are found to carry immunological oddities characteristic of people with lupus, although at the time they show no outward signs of disease. These relatives may be the “sleepers”

who have inherited a susceptibility gene that has so far not been triggered and become active.

Twin Studies

Comparing identical twins is the ideal way to quantify the genetic contribution to the development of a condition. Identical twins are made of identical genetic material: they share the same DNA, the basic building blocks that program living systems. If twins share a characteristic, like blue eyes or a musical ear, they are said to be
concordant.
If they differ they are said to be
dis
cordant. Identical twins start out with a high level of concordance just because they are formed from the same egg and the same DNA. If they are brought up together they also share the same environment, increasing their concordance. Fraternal twins do not come from the same egg; they are only as alike as two siblings, although born at the same time. But they will share their environment if brought up together.

Twin Studies: The Latest

In 2003, to increase our understanding of the role of genetic inheritance in developing autoimmune diseases, the National Institute of Environmental Health Sciences launched a search for same-sex siblings—twins or close-in-age brother or sister pairs—where one sibling had an autoimmune disease but the other did not. (Selecting same-sex, close-in-age pairs eliminates the variability conferred by age and sex differences.) Organizers of the study plan to enroll four hundred pairs, even though it may take a while to recruit such a select grouping. Their hope is that this research will give clearer answers regarding the role of genes that predispose susceptible individuals to whatever triggers autoimmune diseases.

The likelihood that fraternal twins will be concordant for lupus is no more than it is for siblings born at different times—a mere 2 to POL text Q6 good.qxp 8/12/2006 7:39 PM Page 27

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5 percent. But identical twins have a much higher concordance; various studies estimate it to be from 24 percent to as high as 57

percent. From the point of view of quantifying the genetic component in developing lupus, the interesting thing is why it is no more than 57 percent. These children share not only genes; they share environment during childhood. What happened differently to the one who developed lupus? A gene for susceptibility may have been inherited, but it is clearly not the whole story.

Vulnerable Markers

Before we leave the topic of genetic connection there is another inherited component that appears to affect who succumbs to the bite of the wolf and who escapes.

About thirty years ago, when the first organ transplants took place, medical interest became focused upon why and how transplants from a donor were rejected by the recipient’s body. How did each individual body distinguish between “self” and “foreign” and fight the foreign invader as vigorously and efficiently as if it had been merely a splinter or a small cut? Researchers discovered that every human cell carries an inherited code that controls a number of immune responses, including the acceptance or rejection of transplanted tissue and organs.

Everyone belongs to one or another
major histocompatibility complex (histos
is the Greek word for “tissue”), or MHC, just as all of us belong to one of several blood groups that determine what type of donor blood is acceptable for transfusion. If a recipient is in the same MHC as the donor, then the transplant will not be perceived as foreign by the immune system and has a better chance of being accepted by the body. Scientists can now pick up markers for people’s MHC from their blood, just as they are able to read their blood type. These markers are called
antigens,
because they generate

“anti” behavior against an invader, whether it be germs or transplanted tissue. The MHC markers also identify people who may be susceptible to certain diseases.

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In the early 1970s an MHC marker was identified in 80 percent of those with the condition dauntingly named
ankylosing spondylitis,
a disabling form of spinal arthritis that strikes mostly men and had been observed to run in families. The marker was found in only 10

percent of people without the disease. Since then, MHC markers linked to several other diseases have been found, including rheumatoid arthritis, insulin-dependent (type 1) diabetes, and, yes, lupus.

All these are autoimmune conditions, so perhaps it is not surprising that shared inherited factors that affect the operation of the immune system should be common to so many people with these diseases.

Since you inherit your MHC from your parents and grandpar-ents, the same groups tend to run in families. That is why brothers, sisters, or even more distant relatives are sought whenever someone needs a transplant of bone marrow. By the same reasoning, certain MHCs will be more common in some ethnic groups than in others, which goes some way toward explaining why certain racial groups or nationalities may have a higher incidence of some diseases.

Markers for MHCs are not the only clues to understanding lupus that can be detected from tests of the patient’s blood; see Chapter 4 for more on this topic.

“Sometimes It’s Hard to Be a Woman”

Since nine times as many women as men get lupus, surely it seems obvious that femaleness must be to blame, right? Women have two X chromosomes and men have one X and one Y. Could there be something on that second X chromosome that makes women more vulnerable to lupus than men? Or could something on the male Y

chromosome be protecting them? This is exactly how a genetic disease like
hemophilia
(a bleeding disorder) works; it is carried on one X chromosome but in the presence of a second X lies dormant.

That means women carry the disease but never exhibit it. However, if a man inherits the defective X chromosome, his Y chromosome doesn’t suppress the illness. He bleeds.

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We know that it doesn’t work like this for lupus or the differences between the sexes would be much more dramatic and the concordance of twins would be absolute.

So if not chromosomes, what about hormones? Aren’t they part of what makes men and women different? We know that most women develop the disease during their reproductive years, when the sex hormones are most active. One major hospital study of all the children and teenagers who developed lupus over a period of ten years found that a substantial spurt of new cases occurred at the ages of eleven and twelve, the age of puberty.

But if female hormones were responsible for this dramatic phenomenon, you would expect the balance of hormones in those who develop lupus to be noticeably different from the balance in those who do not. (It is the balance between hormones that counts rather than absolute hormone levels.) In one study, female hormones
(estrogens)
were found to aggravate the symptoms of laboratory mice with a lupus-like illness, and male hormones
(androgens)
appeared to protect the mice. However, making an existing illness worse or better is not the same as causing it, and something that protects or cures mice might not work for humans.