• Function of HLA Antigens

• Category 1 Immunological Problems: HLA Compatibility as a Cause for Recurrent Spontaneous Pregnancy Loss

• Category 2 Immunological Problems: Autoantibody Response to Phospholipid Adhesion Molecules

• Category 3 Immunological Problems: Autoimmune Response to Nuclear Components

• Category 4 Immunological Problems: Autoimmune Response to Sperm Antigen

• Category 5 Immunological Problems

  • Chapter 1: CD 56+ Natural Killer Cells

  • Chapter 2: CD 19+ 5+ B Cells (1)

  • Chapter 3: CD 19+ 5+ B Cells (2)

Positive Antinuclear Antibody (ANA)

Category 3 immune problems occur in 22% of women with recurrent pregnancy losses and nearly 50% of women with infertility and IVF failures. Women with this problem make antibodies to DNA, or DNA breakdown products in the embryo or in the pregnancy. These antibodies form first in the blood as IgM. As the problem gets worse they appear as IgG and live in the lymphatic system and lymph nodes. With more losses they form IgA antibodies which have their home and action in the organs including the uterus. These antibodies can be against pure double stranded DNA (ds DNA), single stranded DNA (ss DNA), or smaller molecules called polynucleotides and histones that make up the single strands (see diagram).

Autoantibody
Double Stranded DNA				Inflammation Around the Placenta
Single Stranded DNA
Polynucleotide
Histone

Consequences

• Antinuclear Antibody (ANA) positive, speckled pattern.
  
• Autoantibody to DNA leads to inflammation in the placenta.
  
• Autoimmune disease screening in the woman is negative (No evidence of lupus or rheumatoid arthritis).
  

A blood test determines the presence of antibodies to polynucleotides, histones and DNA. This process involves running 27 different tests on a sample of blood.

The presence of antibodies is also tested for by doing the ANA test. This is a less sensitive test but one that many doctors have already done on their patients before we ever see them.

The test is reported as a titer and a pattern. Any titer above 1:40 is significant. The titers can get into the thousands such as 1:2,500. This simply means that the test is positive when the blood serum is diluted many times.

The pattern is reported as homogeneous, nucleolar or speckled:

• Homongeneous: the antibody is to the ss DNA or ds DNA.
• Nucleolar: the antibody is directed to the polynucleotides.
• Speckled: the antibody is directed against the histones.

Some women demonstrate a mixed pattern of speckled/homogeneous.

These same antibodies appear positive in women with lupus, rheumatoid arthritis, Crohn's disease and other autoimmune diseases. They are usually in high titers. Pregnancy losses, infertility and IVF failures cause the titers to be much lower and a low positive titer does not mean that you have or are getting an autoimmune disease; however, this is ruled out during the testing.

In women with autoimmune diseases these antibodies cause inflammation in joints and organs. In women with no autoimmune diseases but a positive antibody, the antibody causes inflammation around the embryo at the time of implantation or in the placenta after implantation. This inflammation is exactly the same as occurs if you get a splinter under your fingernail. The tissue around the splinter gets hot, red and swollen and it happens quickly.