How Man Becomes Allergic To Parts of Himself

Though men and women suffer misery-making allergic reactions to countless things, from ragweed pollen to wheat or eggs or the Rh factor from a husband's blood, medical researchers are confident that no one person can be allergic to another. But now there is a fast-growing body of evidence that something much more insidious and harder to understand may cause some of man's most common and crippling disorders. People, it seems, can become allergic to parts of themselves.

This arcane process of "auto-allergy" may be an important factor in many cases of anemia, in rheumatoid arthritis and myasthenia gravis, and in kidney and thyroid diseases. Last week, at the second of two Manhattan conferences on what many doctors prefer to call "autoimmune disease," researchers added impressive evidence on two recent additions to the catalogue of such ills: ulcerative colitis and pernicious anemia.

"Know Thyself." Boston Hematologist Dr. William Dameshek of the Tufts-New England Medical Center pioneered the concept of autoimmune disease. It has long been accepted dogma that in ordinary healthy immune reactions the body is using a birthright of every living creature. This is a set of biochemical sentries which raise an alarm when the body is invaded by a foreign substance, especially a protein, so that the system can make antibody to neutralize the invader. "Normally," says Dr. Dameshek, "the body has safeguards so it can recognize 'self as opposed to 'not-self,' and it will not damage 'self materials. Occasionally these safeguards break down." Dr. Dameshek detected such a breakdown in 1937 when he was treating three patients for severe hemolytic ("blood-destroying") anemia. They needed transfusions, but in the blood of each patient the doctor found a factor that made cross-matching difficult. He discovered that both the donors' blood cells and the patients' own were being destroyed by an antibody mechanism. Dr. Dameshek deduced that the patients had developed antibodies against their own cells.

"This started us off on the idea that some people, for some reason, somehow develop antibody mechanisms which act against one of their own body constituents--which may be red cells, white cells or whole organs. For years we cried in the wilderness. We were called wild-eyed visionaries. Critics asserted that the human body should not, cannot and will not develop such a mechanism of self-destruction." By now Dr. Dameshek has far more supporters than detractors. Many of the supporters, Dr. Dameshek complains, accept his concept only if they can give it another name, "auto-allergy."

From Eye to Eye. The most clear-cut and comprehensible autoimmune diseases form a small, exceptional group. Thousands of the body's countless proteins circulate in the blood or are washed by it, but a few are "sequestered": the fluid in the eye's lens, sperm secreted in the testicles, and thyroglobulin (an iodine-containing protein), which usually stays locked in the thyroid gland. If lens fluid leaks into the bloodstream after injury, its proteins start the antibody factory working and the body seeks to destroy the lens proteins.

That this is actually an autoimmune reaction, with antibody circulating in the blood, is shown by the fact that if only one eye is injured, the antibody gets to the other eye and attacks the proteins in its lens. Thus injury to one eye may lead to blindness in both. Injury or inflammation of the testicles may force sperm proteins into the bloodstream, which then sets about destroying them--a process that causes temporary or even permanent sterility. If the thyroid gland is damaged or diseased, thyroglobulin may escape from its sequestered state, and a clearly defined form of thyroid disease results.

Fascinating Mono. In these three cases, it is easy enough to understand how the body can regard the escaping antigen-protein as "new" or "foreign," because it has been sequestered for years, perhaps since the fetal stage. Far more knotty are the questions that arise so often in Dr. Dameshek's practice as a hematologist. No less than 50% of all blood-destroying anemias acquired after infancy, he believes, are the results of autoimmune reactions. He is so confident of this that he abbreviates the disorders to AIHA--autoimmune hemolytic anemias.

Among victims of the half-dozen or more familiar forms of leukemia, he says, it is common for an AIHA process to develop at some stage of the disease. In the AIHA phase, though red cells are the likeliest victims of autoimmune destructive processes, it is not unusual for the platelets (the tiniest solids in the blood, essential for clotting) to be destroyed.

"From this," Dr. Dameshek told the New York Academy of Sciences, "it is only a step to the thought that autoimmune reactions and certain types of leukemia might occur simultaneously, and in fact be one and the same thing." What makes this possibility especially intriguing is the fact that no "cause" of leukemia is known, though there is increasing evidence that it may be triggered by a virus.

Dr. Dameshek has built a research bridge from the leukemias, or "blood cancers," to infectious mononucleosis, which he calls a "fascinating disease." It is, he says, at one and the same time an infection (presumably caused by a virus), a complex immune reaction, and an atypical, self-limiting form of leukemia. In "mono," several abnormal types of antibody are found at the times when the patient's lymph glands are overactive. Where the "not-self" or foreign proteins come from to start this process is not certain, but the likeliest source is the original virus, acting on lymph cells. And Dr. Dameshek notes that in three familiar diseases definitely known to be caused by viruses--German measles, viral pneumonia and poliomyelitis--there is occasionally a temporary autoimmune phase with blood-cell destruction.

Circulating & Bound. Among generalized and severe diseases, one is now widely accepted as resulting from autoimmune reactions. Forbiddingly called systemic lupus erythematosus, or SLE (it has no simple English name), it is being recognized as much more common than doctors once believed. It has a predilection for women of childbearing age. SLE takes a bewildering variety of forms, usually beginning with skin eruptions or joint pains, and progressing to such seemingly unrelated illnesses as arthritis, clotting disorders, and even psychotic episodes. It may prove fatal within ten years. What seems to mark SLE most clearly as an autoimmune disease is that victims have a variety of abnormal antibody types as bewildering as their symptoms.

Other diseases are more difficult to classify as autoimmune because there is no clear-cut definition of antibody. There are at least two main kinds and perhaps a third. Best-known are the protein molecules found in the blood's gamma globulin. It is because of them that gamma globulin gives short-lived protection against many viral diseases to people who have never been infected or vaccinated and therefore have not made their own antibodies (for example, measles, German measles, hepatitis). The second major class consists of antibodies that do not circulate, but are "bound" in the tissues. A proposed third class comprises those that circulate in the lymph system.

Mistaken Identity. Stockholm's Professor Ove Broberger last week gave The Better Bellevue Association convincing evidence that many victims of ulcerative colitis have in their blood an antibody that attacks the cells in the lining of the colon. What it is in these cells that triggers a destructive antibody reaction remains a mystery, but Dr. Broberger noted that colitis often follows bacterial infections. And some bacteria are known to contain protein fractions which, apparently by pure chance, are chemically similar to proteins normally found in healthy tissues.

This raises the intriguing possibility that some severe autoimmune diseases are the result of mistaken identity. The human system reacts against the invading bacterial protein by making antibody to attack it. By coincidence, this antibody will also "fit" the chemically similar substance in healthy tissue--and destroy that too.

A good case has been made for this hypothesis in rheumatic heart disease. This crippling infirmity begins with a "strep throat." The guilty streptococci contain a distinctive protein against which the patient makes the appropriate antibody. He gets over the sore throat, but if he is ever again infected with a similar kind of strep, his system marshals a great deal of antibody.

Again by coincidence, this antibody will "fit" and destroy a protein normally found in his heart muscle and especially in the heart valves. Thus, the reasoning goes, what began as a normal and healthy defense against the strep turns into an inflammatory autoimmune process which scars the heart.

Missing Messenger. Pernicious anemia has remained a mysterious disease despite the finding that it can be controlled (though not cured), first by liver extracts and now by vitamin B12. Cornell University's Dr. Graham Jeffries began by studying the inflammation of the stomach lining that precedes pernicious anemia. This robs the patient of a biochemical messenger which normally conveys B12 through the digestive system to the body. In patients' blood, Dr. Jeffries reported, he has found antibody of a type that attacks the stomach-lining cells.

It is too easy to assume, warns New York University's Dr. Lewis Thomas, that because immune reactions are detected in a patient they must have caused his illness. In many cases, he suggests, they may be a result of it rather than a cause. On both sides of such questions, the Manhattan conferees agreed, much more must be learned. There is good reason for intensified research, because so many of the diseases now classed as autoimmune are crippling or even rapidly fatal, and for most of them there is no effective treatment, let alone a cure.

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