Doctor performed groundbreaking research on causes of allergic reactions

Kimishige Ishizaka, an immunologist whose experimental work — including transforming himself into a human pin cushion — identified the antibodies that trigger wheezing, itching, rashes and other allergic reactions, died July 6 in Yamagata, Japan. He was 92.

His death was announced by the La Jolla Institute for Allergy and Immunology in California, where he had been scientific director and president.

By developing a better understanding of what causes severe allergic reactions in hypersensitive individuals, Dr. Ishizaka and his wife, Teruko Ishizaka, a research immunologist, laid the groundwork in the mid1960s for advances in monitoring, treating and preventing such conditions as asthma, hay fever and drug and food allergies.

More recently, he cautioned in an interview in the book “History of Allergy” (2014) that the number of allergy patients had been increasing in developed countries, apparently as a result of environmental factors like air conditioning, heating and exposure to certain products.

He said the increase might also be attributed to what is called the “hygiene hypothesis,” which posits that fewer people are building up resistance to potentially harmful antibodies because of declining infection rates.

For decades, researchers had been studying a protein molecule called reagin, which was implicated in allergic conditions. Dr. Ishizaka asked his colleagues to inject solutions of the molecule into his back. At the time, he and his wife were working at the Children’s Asthma Research Institute and Hospital — now National Jewish Health — in Denver, where Dr. Ishizaka eventually became chief of immunology.

The injections prompted his body to produce specific antibodies, so-called defensive proteins in the blood, which served to protect against disease introduced into the body by a foreign substance. His team identified the class of proteins as Immunoglobulin E, better known as IgE. It was considered a medical milestone.

Dr. Ishizaka not only identified the antibody but also deciphered how it worked — through a lock-and-key binding factor, which connects one end of the antibody to the offending foreign substance and the other end to a white blood cell called a mast cell.

Normally, once the foreign substance, the antibody and the mast cell are linked, the mast cell secretes histamine and another chemical. That causes an individual to sneeze and expel the pollen or other allergen.

In a person suffering from allergies, though, too much IgE stimulates an extra release of histamine, a compound that causes dilation of capillaries. That, in turn, results in excessive sneezing and other symptoms, including some that could be more serious.

Dr. Ishizaka’s team published its findings in 1966.

In 1969, the Ishizaka team and another headed by S.G.O Johansson and Hans Bennich in Uppsala, Sweden, collaborated in publishing similar findings.

For nearly two decades, beginning in 1970, the Ishizakas conducted research at Johns Hopkins University, where Dr. Ishizaka was an assistant professor of biology, medicine and microbiology. In 1989, he was named scientific director of the then-new La Jolla Institute; he became its president in 1991.

He retired in 1996 and returned to Japan, settling in Yamagata, his wife’s hometown, in northern Japan.