Help with Interpreting Immune Test Results
Information gathered from Reproductive Immunology Support Group discussions
Disclaimer: This document to be used as a general guide only. Information contained in this document is not to be taken as medical advice.
Contents
I. Guide to interpreting the Natural Killer Cell Assay
II. Guide to interpreting the Th1/Th2 Cytokine assay
I. Guide to interpreting the Natural Killer Cell Assay
Normal NK Assay
NK Cells (Killers) : Embryo Cell (Targets) ratio
50:1 10%
25:1 5%
12:1 2.5%*
*Percent embryo targets killed
Abnormal NK Assay
NK Cells (Killers): Embryo Cell (Targets) Ratio
50:1 40%
25:1 20%
12:1 10%*
*Percent placental targets killed
Guidelines
Any killing percentage in any tube dilution (50:1. 25:1, 12:1) above 15% will damage the embryo. The aim is to reduce the killing power of the natural killer cells to below 15% before the cycle of conception and this may take three months in some women.
The NK assay also gives the physician and the patient the following data:
1. CD 19+ cells (often elevated)
2. CD3 cells (often elevated)
3. CD 56+ cells (usually elevated, but not always)
4. CD 19+5+ (usually elevated, but not always)
1. CD3 cells (These are T cells)
CD-3 (Pan T-Cells) 63-86%
These cells are the most important in our immune system. They are low when the immune system is weak (suppressed) and normal when the immune system is healthy. Infertile patients and patients with recurrent pregnancy losses have values in the high normal range. These individuals have immune systems that are strong - even overactive. A strong overactive immune system is associated with a 5% incidence of autoimmune diseases for example, thyroiditis, lupus, rheumatoid arthritis.
2. CD 19+ cells (These are B cells)
CD-19 (B Cells) Normal Range 3-8%
CD-19 B cells are almost always high normal or very elevated in women with an immune cause for their infertility or recurrent pregnancy losses. There is often a greater than 12% elevation. This is one of the most important indicators of an immune problem and that the immune system is working overtime. Endometriosis also primes this system into greater hyper-reactivity.
3. CD 56+ cells (NK cells)
CD 56+ Natural Killer Cells 3-12%
These Natural Killer (NK) Cells include CD56+/16+ Natural Killer Cells and CD56+ Natural Killer cells with lack of a CD16 molecule. Natural Killer Cells are activated by a pregnancy that fails or a fertilized embryo that degenerates. CD56+/16+ Natural Killer Cells are produced in the decidua and they are even more geared up to kill than those from the bone marrow. They produce large quantities of Tumor Necrosis Factor locally that kills the placental cells and the fetal cells. The normal range of CD56+ Natural Killer cells is 3-12%. Levels of 18% or greater correlate with poor reproductive outcome.
4. CD 19+5+ cells
CD 19+/5+ (B-1 Cells) Normal Range 2-10%
When this population of cells is activated, they produce polyclonal antibodies to hormones, hormone receptors and neurotransmitters. The hormones most usually attacked by these antibodies are thyroid hormones, estrogens, progesterone, gonadotropins and growth hormone. Women with elevations of these cells may be at risk for thyroiditis and the premature menopause. Patients whose levels are 80-90% often stimulate poorly with gonadotropins. Women with high levels often complain of immunological symptoms when stimulated with gonadotropins. These symptoms include joint pain, finger stiffness, headache, lethargy, malaise, fever, depression and occasionally urticaria and hives. These cells like the CD 3/IL-2R+ cells are elevated in autoimmune disorders and in situations where a person is rejecting a bone marrow transplant from a compatible donor. There is no question that they are involved in early embryonic loss or damage.
Will intravenous Immunologlobulin (IVIg) Added to the Test Tube Reduce the killing to below 15%?
This is part of the full NK assay test, not a part of the follow up test after the patient has IVIg in her system.
Natural Killer: Placental Target Cell Ratio with and without Adding IVIg to the Test Tubes
No IVIG Added
50:1 40%
25:1 37%
12:1 22%
6.25 mg/ml IVIG added
(One day dose)
50:1 35%
25:1 30%
12:1 11%
12.5 mg/ml IVIg added
(Three day dose)
50:1 15%
25:1 10%
12:1 9%
Interpretation
1. High NK cell killing.
2. Adequate suppression with 12.5 mg/ml of IVIg. This translates into a dosage for the patient of 25 grams daily x 3 days on day 6,7 and 8 of the cycle of conception.
II. Interpreting the TH1 TH2 Cytokine assay
The TH1/TH2 intracellular cytokine assay simply counts the "bad cells” (TH1 cells) and the "good cells" (TH2 cells). Results are given as two ratios:
1. the ratio of TNF alpha bearing “bad cells” cells to IL-10 bearing cells “good cells” (TNFa/IL-10); and
2. the ratio of the Interferon Gamma bearing cells “bad cells” to IL-10 bearing cells “good cells” (IFNg/IL-10).
Reference ranges (non-pregnant)
TNF alpha /IL-10 5.6-21
IFN gamma/IL10 13.2-30.3
Reference ranges were taken from the Laboratory for Reproductive Medicine& Immunology, 7013 Realm Dr, San Jose, California, USA 95119.
Information gathered from Reproductive Immunology Support Group discussions
Disclaimer: This document to be used as a general guide only. Information contained in this document is not to be taken as medical advice.
Contents
I. Guide to interpreting the Natural Killer Cell Assay
II. Guide to interpreting the Th1/Th2 Cytokine assay
I. Guide to interpreting the Natural Killer Cell Assay
Normal NK Assay
NK Cells (Killers) : Embryo Cell (Targets) ratio
50:1 10%
25:1 5%
12:1 2.5%*
*Percent embryo targets killed
Abnormal NK Assay
NK Cells (Killers): Embryo Cell (Targets) Ratio
50:1 40%
25:1 20%
12:1 10%*
*Percent placental targets killed
Guidelines
Any killing percentage in any tube dilution (50:1. 25:1, 12:1) above 15% will damage the embryo. The aim is to reduce the killing power of the natural killer cells to below 15% before the cycle of conception and this may take three months in some women.
The NK assay also gives the physician and the patient the following data:
1. CD 19+ cells (often elevated)
2. CD3 cells (often elevated)
3. CD 56+ cells (usually elevated, but not always)
4. CD 19+5+ (usually elevated, but not always)
1. CD3 cells (These are T cells)
CD-3 (Pan T-Cells) 63-86%
These cells are the most important in our immune system. They are low when the immune system is weak (suppressed) and normal when the immune system is healthy. Infertile patients and patients with recurrent pregnancy losses have values in the high normal range. These individuals have immune systems that are strong - even overactive. A strong overactive immune system is associated with a 5% incidence of autoimmune diseases for example, thyroiditis, lupus, rheumatoid arthritis.
2. CD 19+ cells (These are B cells)
CD-19 (B Cells) Normal Range 3-8%
CD-19 B cells are almost always high normal or very elevated in women with an immune cause for their infertility or recurrent pregnancy losses. There is often a greater than 12% elevation. This is one of the most important indicators of an immune problem and that the immune system is working overtime. Endometriosis also primes this system into greater hyper-reactivity.
3. CD 56+ cells (NK cells)
CD 56+ Natural Killer Cells 3-12%
These Natural Killer (NK) Cells include CD56+/16+ Natural Killer Cells and CD56+ Natural Killer cells with lack of a CD16 molecule. Natural Killer Cells are activated by a pregnancy that fails or a fertilized embryo that degenerates. CD56+/16+ Natural Killer Cells are produced in the decidua and they are even more geared up to kill than those from the bone marrow. They produce large quantities of Tumor Necrosis Factor locally that kills the placental cells and the fetal cells. The normal range of CD56+ Natural Killer cells is 3-12%. Levels of 18% or greater correlate with poor reproductive outcome.
4. CD 19+5+ cells
CD 19+/5+ (B-1 Cells) Normal Range 2-10%
When this population of cells is activated, they produce polyclonal antibodies to hormones, hormone receptors and neurotransmitters. The hormones most usually attacked by these antibodies are thyroid hormones, estrogens, progesterone, gonadotropins and growth hormone. Women with elevations of these cells may be at risk for thyroiditis and the premature menopause. Patients whose levels are 80-90% often stimulate poorly with gonadotropins. Women with high levels often complain of immunological symptoms when stimulated with gonadotropins. These symptoms include joint pain, finger stiffness, headache, lethargy, malaise, fever, depression and occasionally urticaria and hives. These cells like the CD 3/IL-2R+ cells are elevated in autoimmune disorders and in situations where a person is rejecting a bone marrow transplant from a compatible donor. There is no question that they are involved in early embryonic loss or damage.
Will intravenous Immunologlobulin (IVIg) Added to the Test Tube Reduce the killing to below 15%?
This is part of the full NK assay test, not a part of the follow up test after the patient has IVIg in her system.
Natural Killer: Placental Target Cell Ratio with and without Adding IVIg to the Test Tubes
No IVIG Added
50:1 40%
25:1 37%
12:1 22%
6.25 mg/ml IVIG added
(One day dose)
50:1 35%
25:1 30%
12:1 11%
12.5 mg/ml IVIg added
(Three day dose)
50:1 15%
25:1 10%
12:1 9%
Interpretation
1. High NK cell killing.
2. Adequate suppression with 12.5 mg/ml of IVIg. This translates into a dosage for the patient of 25 grams daily x 3 days on day 6,7 and 8 of the cycle of conception.
II. Interpreting the TH1 TH2 Cytokine assay
The TH1/TH2 intracellular cytokine assay simply counts the "bad cells” (TH1 cells) and the "good cells" (TH2 cells). Results are given as two ratios:
1. the ratio of TNF alpha bearing “bad cells” cells to IL-10 bearing cells “good cells” (TNFa/IL-10); and
2. the ratio of the Interferon Gamma bearing cells “bad cells” to IL-10 bearing cells “good cells” (IFNg/IL-10).
Reference ranges (non-pregnant)
TNF alpha /IL-10 5.6-21
IFN gamma/IL10 13.2-30.3
Reference ranges were taken from the Laboratory for Reproductive Medicine& Immunology, 7013 Realm Dr, San Jose, California, USA 95119.
