What Is an Autoimmune Disorder?

Primary immune thrombocytopenia is an autoimmune disorder, which means that it develops when the body’s immune system starts to attack cells in the body that are not harmful by mistake. The immune system protects the body from things that are potentially harmful by recognizing “antigens”, which is a term used to describe anything that causes an immune response and can include chemicals or molecules on the surfaces of bacteria and viruses.

The cells in your body also have molecules on their surfaces, but the immune system usually recognizes them as “self-antigens”. In other words, the immune system knows that they are not “foreign” and should not be attacked. However, sometimes the body’s immune system starts to recognize self-antigens as foreign ones and begins to attack them. This is an “autoimmune” response and can result in the destruction of normal, healthy body tissue, or changes in the function of or the abnormal growth of an organ. Autoimmune disorders include type 1 diabetes, rheumatoid arthritis, and multiple sclerosis.

What Are the Symptoms of Primary Immune Thrombocytopenia?

The main symptom of primary immune thrombocytopenia is a low number of platelets in the blood. Blood is made up of a liquid called plasma and three main types of blood cells:

1. Red blood cells carry oxygen around the body.
2. White blood cells fight infection and there are several different types, including lymphocytes (the main type of white blood cell found in the lymph fluid that circulates around the body) called B cells and T cells.
3. Platelets are the third type of blood cell and are involved in the process that enables blood to clot to promote healing and control blood loss.

In people with primary immune thrombocytopenia the immune system starts to mistakenly attack platelets in the blood, stopping them from working or breaking them down. This results in reduced levels of platelets in the blood, which can result in excessive bleeding because the blood is less able to clot. Although the symptoms of primary immune thrombocytopenia vary between patients, common symptoms include spontaneous bruising or bruising easily, bleeding from the gums, blood blisters on the insides of the cheeks, frequent heavy nose bleeds that are hard to stop, and fatigue.

How Do Immune Cells Contribute to Primary Immune Thrombocytopenia?

There is some evidence that abnormalities in the function and number of some types of immune cell are associated with primary immune thrombocytopenia. The immune system can be thought of as having two branches:

• The first, the “innate immune system”, includes the inflammatory response and does not have the ability to “remember” antigens that it has encountered.
• The second, the “adaptive immune system”, does have memory, which means that if the immune system has encountered an antigen once before it will be able to mount a stronger response if it encounters it again, a property that is exploited by vaccines.

B and T cells are the main mediators of the adaptive immune system. B cells have immunoglobulin molecules on their surfaces that act as receptors that recognize antigens and can be secreted as antibodies. T cells have specific antigen receptors called T-cell receptors on their surfaces that other types of lymphocyte do not have.

What Do T Cells Do?

There are three different types of T cells with different functions:

1. Cytotoxic T cells can directly kill virus-infected cells and cancer cells (cytotoxic means toxic to cells or “cell killing”).
2. Helper T cells help to activate other cells in the immune system, like B cells and cytotoxic T cells, and play a role in regulating the responses of the immune system.
3. Regulatory T cells play important roles in the immune system’s ability to recognize self-antigens, and a type of these called T follicular regulatory (Tfr) cells can also suppress the functions of B cells and influence the breakdown of T helper cells.

What Did This Study Show?

The exact mechanisms by which changes in the immune system lead to the development of primary immune thrombocytopenia are currently unknown. If these changes can be better understood it may be possible to target parts of the immune system that become dysregulated during the development of primary immune thrombocytopenia as a way of treating the condition.

The authors of this study therefore compared blood samples from people with primary immune thrombocytopenia with blood samples donated by people without the condition, and looked for differences in gene expression and numbers of different types of T cells. (Gene expression is the process by which the information encoded by a gene is translated into a function, usually through the production of a protein, by being switched on or off or by the activity of the gene being increased or reduced.)

The results of the study showed that there were a number of genes that were expressed differently in patients with primary immune thrombocytopenia compared with people without the condition that were mainly involved in immune responses and the process of inflammation. In particular, there were differences in the proportions of Tfr and T follicular helper (Tfh) cells, and the proportions of these cell types also changed when patients with primary immune thrombocytopenia responded to treatment. The levels of Tfh cells were increased in patients with primary immune thrombocytopenia but decreased after they responded to treatment, while the ratio of Tfh cells to Tfr cells increased after treatment responses.

In addition, two genes were much more highly expressed in people with primary immune thrombocytopenia than in people without the condition. BCL-6 encodes a protein that regulates the proliferation of Thf cells, while IL-21 encodes a protein that is able to increase the differentiation of Thf cells and also suppress the differentiation of Tfr cells.

Note: This post is based on an article that is not open-access; i.e., only the abstract is freely available.