Microchimerism is the presence of a small number of cells that originate from another individual and are therefore genetically distinct from the cells of the host individual. This phenomenon may be related to certain types of autoimmune diseases; however, the mechanisms responsible for this relationship are unclear.

Human

In humans (and perhaps in all Placentals) the most common form is fetomaternal microchimerism (also known as fetal cell microchimerism or fetal chimerism) whereby cells from a fetus

Fetus

A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...

 pass through the placenta

Placenta

The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...

 and establish cell lineages within the mother. Fetal cells have been documented to persist and multiply in the mother for several decades. The exact phenotype

Phenotype

A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...

 of these cells is unknown, although several different cell types have been identified, such as various immune lineages, mesenchymal stem cells, and placental-derived cells. The potential health consequences of these cells are currently unknown. One hypothesis is that these fetal cells might trigger a graft-versus-host reaction

Graft-versus-host disease

Graft-versus-host disease is a common complication after a stem cell transplant or bone marrow transplant from another person . Immune cells in the donated marrow or stem cells recognize the recipient as "foreign". The transplanted immune cells then attack the host's body cells...

 leading to autoimmune disease

Autoimmune disease

Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...

. This offers a potential explanation for why many autoimmune diseases are more prevalent in middle-aged women. The other main theory is that fetal cells home to injured or diseased maternal tissue where they act as stem cells and participate in repair. It is also possible that the fetal cells are merely innocent bystanders and have no effect on maternal health.

After giving birth, about 50-75 % of women carry fetal immune cell lines. Maternal immune cells are also found in the offspring yielding in maternal→fetal microchimerism, though this phenomenon is about half as frequent as the former .

Microchimerism had also been shown to exist after blood transfusion

Blood transfusion

Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...

s to a severely immunocompromised population of patients who suffered trauma

Physical trauma

Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...

.

Animal

Microchimerism occurs in most pairs of twins in cattle

Cattle

Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...

. In cattle (and other bovine

Bovinae

The biological subfamily Bovinae includes a diverse group of 10 genera of medium to large sized ungulates, including domestic cattle, the bison, African buffalo, the water buffalo, the yak, and the four-horned and spiral-horned antelopes...

s), the placenta

Placenta

The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...

e of fraternal twins usually fuse and the twins share blood circulation, resulting in exchange of cell lines. If the twins are a male-female pair, the male hormones from the bull calf have the effect of partially masculinising the heifer (female), creating a martin heifer or freemartin

Freemartin

A freemartin or free-martin is an infertile female mammal which has masculinized behavior and non-functioning ovaries. Genetically and externally the animal is female, but it is sterilized in the womb by hormones from a male twin, becoming an infertile partial intersex...

. Freemartins appear female, but are infertile and so cannot be used for breeding or dairy production

Dairy farming

Dairy farming is a class of agricultural, or an animal husbandry, enterprise, for long-term production of milk, usually from dairy cows but also from goats and sheep, which may be either processed on-site or transported to a dairy factory for processing and eventual retail sale.Most dairy farms...

. Microchimerism provides a method of diagnosing the condition, because male genetic material can be detected in a blood sample.

Relationship with autoimmune diseases and breast cancer

Microchimerism has been implicated in autoimmune diseases. Independent studies repeatedly suggested that microchimeric cells of fetal origin may be involved in the pathogenesis of systemic sclerosis. Moreover, microchimeric cells of maternal origin may be involved in the pathogenesis of a group of autoimmune diseases found in children, i.e. juvenile idiopathic inflammatory myopathies (one example would be juvenile dermatomyositis

Juvenile dermatomyositis

Juvenile dermatomyositis is an autoimmune disease causing vasculitis that manifests itself in children; it is the pediatric counterpart of dermatomyositis. In JDMS, the body's immune system attacks blood vessels throughout the body, causing inflammation called vasculitis...

). Microchimerism has now been further implicated in other autoimmune diseases, including systemic lupus erythematosus

Lupus erythematosus

Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...

. Contrarily, an alternative hypothesis on the role of microchimeric cells in lesions is that they may be facilitating tissue repair of the damaged organ.

Moreover, fetal immune cells have also been frequently found in breast cancer stroma as compared to samples taken from healthy women. It is not clear, however, whether fetal cell lines promote the development of tumors or, contrarily, protect women from developing breast carcinoma.

Microchimerism and disease within the context of a tripartite conflict

A recent hypothesis interprets this relationship by considering fetal, maternal, and paternal adaptive interests separately and in interaction with one another. Theoretically, fetuses may benefit from immunological information gathered by their migrant immune cells in the maternal body provided that many of them return into the fetus. They may also benefit from improved maternal defense, provided that fetal cell lines (carrying partly paternal resistance alleles) contribute to maternal defense against pathogens or tumors. However, fetuses may be jeopardized by a selfish maternal usage of fetomaternal microchimerism – i.e. some mothers get pregnant only to improve their immune system and then to abort. The use of microchimeric cells by the maternal immune system may contribute to the adaptive benefits of female choosiness

Sexual conflict

Sexual conflict occurs when the two sexes have conflicting optimal fitness strategies concerning reproduction, particularly the mode and frequency of mating, leading to an evolutionary arms race between males and females. The conflict encompasses the actions and behaviors of both sexes to influence...

 and polyandry

Polyandry

Polyandry refers to a form of marriage in which a woman has two or more husbands at the same time. The form of polyandry in which a woman is married to two or more brothers is known as "fraternal polyandry", and it is believed by many anthropologists to be the most frequently encountered...

. While fathers may enjoy an indirect benefit from enhanced fetal and maternal health, they also face the risk of wasting their sexual efforts due to selfish pregnancies of cheating females. Paternal alleles acting via clones of microchimeric cells in the maternal body could launch an immunological attack against the non-kin sperm in the female genitalia, or against the non-kin fetus in the womb. Thus microchimeric cells carrying partly the alleles of a former father may launch an attack on a new embryo fathered by a new male. Furthermore, an intraspecific version of Zahavi

Amotz Zahavi

Amotz Zahavi is an Israeli evolutionary biologist, a Professor Emeritus at the Zoology Department of Tel Aviv University, and one of the founders of the Society for the Protection of Nature in Israel...

’s Mafia Hypothesis could explain a potential interaction between the abortion of fetuses and a subsequent rise of an autoimmune disease. This hypothesis suggests that males may be capable of provoking microchimerism-induced autoimmune-like diseases in the mother in revenge of selfish pregnancies. This hypothetic paternal threat could increase the maternal costs associated to selfish pregnancies, thus reduce the chance that males just waste their efforts.

According to the traditional medical thinking, autoimmune disease may cause infertility, habitual abortion and miscarriage. However, this interpretation does not explain why autoimmune diseases (at least several types of them) occur mostly in women, and cannot explain why miscarriage tends to precede the rise of autoimmune problems.

On the contrary, considering the tripartite immune conflict among the fetus, the mother and father as realized by means of a two-way traffic of immune cells through the placenta can nicely explain these phenomena.