What, besides a PI, might explain the high rate of infections? Normal immune responses can be suppressed by many factors, including malnutrition, injuries such as burns, and certain types of drugs (corticosteroids, for instance). Immune responses can also be muted by some diseases, such as leukemia, and some infections, including: infectious mononucleosis (mono), measles, chicken pox, and AIDS. In fact, almost every serious illness impairs the immune responses.

• Physical examination: Is the child well-nourished and growing well? A severely immunodeficient child is likely to look sickly and pale. Very often the child is underweight and lags behind in growth and development.

The child may be shy or quiet. An active, robust, healthy-looking child is less likely to have a serious immune deficiency.

The doctor will listen for changes in the lungs and look for rashes, sores, thrush in the mouth, an enlarged spleen or liver, and swollen joints. Some immunodeficient children may lack palpable tonsils or lymph nodes in the neck.

• Family history. Have any family members or relatives ever been diagnosed with PI or shown an unusual susceptibility to infections? Have there been any infant deaths from infections? Were only boys affected?

E V A L U A T I N G    I M M U N E   R E S P O N S E S

To find out if illness can be traced to an immunodeficiency, laboratory tests are necessary. These tests, most of which can be performed on a sample of blood, probe the soundness of the various parts of the immune system. Are all the right immune cells present, in adequate numbers, and are they working properly? Are there normal amounts and types of antibodies?

Screening starts out with a few relatively simple and inexpensive routine tests. In fact, just two routine tests—complete blood count and quantitative immunoglobulins—will detect most, but not all, immunodeficiencies AND immunoglobulins.

If antibodies are normal—or if the patient’s infections seem to be caused by viruses or fungi—the T cells should be checked. If the T cells are present in normal numbers and function normally, phagocyte function should be evaluated.

The most common screening tests include:

• Blood count. A complete blood count (CBC) shows levels of red blood cells and white blood cells as well as platelets. A "differential count" itemizes the different types of white blood cells, including lymphocytes and neutrophils.

• Quantitative immunoglobulins. This standard laboratory test measures various immunoglobulin levels in the blood. In addition to total immunoglobulins, it shows levels of the different immunoglobulin types (IgG, IgM, and IgA).

• Antibody responses. Are immunoglobulins working properly? A blood test can show if the blood contains antibodies to the usual childhood immunizations, i.e., tetanus, measles, pertussis, or diphtheria. Sometimes a person may be given a booster shot, or a specific immunization such as a tetanus shot, to see if she or he responds by producing antibodies.

• Complement. A laboratory test using a sample of blood indicates how effectively the complement system is working.

• Skin tests. These tests, which are similar to TB skin tests, show how well T cells are functioning. Tiny amounts of several standard reaction-provoking antigens (including mumps and Candida) are injected into the skin. A person with a healthy immune system usually develops local swelling within 24 to 48 hours. However, these tests are not as accurate in very young infants.

When screening tests indicate an immunodeficiency—or when they fail to explain a stubborn infection—additional tests will likely be needed. There are dozens of sophisticated tests that allow doctors to identify and count subsets of B cells and T cells, and to assess subtle abnormalities in antibodies, immune cells, and immune tissues. Tests can also probe the characteristics of infectious germs.

E V A L U A T I N G    I N F E C T I O N S

If an infection proves resistant to standard treatments, the doctor will want to find out exactly what germs are involved. Samples of mucus, sputum, or stool, or sometimes a small sample of the infected tissue itself, removed surgically, can be "cultured" in the laboratory. This allows germs to grow until they are plentiful enough to study in detail. Once the germ is identified, it becomes possible to select the most effective treatment.

The infection itself often provides a good clue to the nature of an immune defect. Common bacteria typically elicit antibodies, while viruses and fungi stimulate T cells. Thus, sinus infections and respiratory infections, which are most often due to bacteria, suggest an antibody deficiency. Infections caused by a variety of viruses and fungi, or by Pneumocystis, point to a T cell defect. Recurrent infections involving the skin or soft tissues can often be traced to problems with phagocytes. Blood-borne infections caused by encapsulated bacteria, including meningitis, may be linked to complement deficiencies.

An experienced physician will also find clues in particular combinations of details, such as age and sex, along with the physical findings. For example, a young infant suffering from diarrhea, pneumonia, and thrush, and exhibiting "failure to thrive," may well have SCID. A 4-year-old with swollen lymph glands, skin problems, pneumonia, and bone infections may have Chronic Granulomatous Disease (CGD). A 10-year old with sinus and respiratory infections, an enlarged spleen, and signs of autoimmune problems is apt to have Common Variable Immunodeficiency.

P R E N A T A L   D I A G N O S I S

Some PIs can be detected even before birth. Prenatal testing may be sought by families that have already had a child with a PI.

Cells for prenatal diagnosis can be obtained in several ways. In amniocentesis at about 14 weeks of pregnancy or later, a small amount of amniotic fluid containing cells shed by the fetus is removed from the uterus. In chorionic villus sampling, cells are taken from the chorion, the tissue that becomes the placenta, as early as 9–10 weeks of pregnancy. After about the 18th week of pregnancy, it is possible to obtain a sample of blood from the fetus.

Prenatal tests make it possible to identify abnormalities in cells or, in the case of some deficiencies, of enzymes. In disorders where a gene mutation has been identified, DNA from fetal cells can be checked for the gene defect.

In some cases, test results make it possible to be ready to treat the baby with a bone marrow transplant soon after birth. Intrauterine bone marrow transplantation of the fetus is also being studied.

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