Alopecia areata involves the production of autoantibodies and inflammatory cells

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  Autoantibodies and Cellular Abnormalities in Alopecia Areata
 
It is now widely accepted that alopecia areata is an autoimmune disease. While the etiology of the disease is still unknown, it is almost certain that it has a linkage with the abnormal functioning of the immune system and the presence of various autoantibodies.

Many believe that the T-cells are responsible for alopecia areata occurrence, if not its maintenance. There are three types of T-cells.

  • Killer or Circulating T cell: This is a cell with an endogenously produced receptor for antigen, and destroys a specifically targeted cell by using the receptor to bind itself to the targeted cell.
  • T helper cell or Effector T cell: These are a group of lymphocytes or white blood cells that coordinate the actual immune response of the body. These cells cannot kill any foreign cells but help other cells perform this task. On their own they are useless against any infection.
  • Suppressor T-cells are involved with suppressing an immune response.

A part of the immune system is the class I and II Major Histocompatibility Complex or MHC proteins. The role of MHC is to present and bind the antigen to the T-cell. The class I MHC is present in almost all cells while class II cells are present only in Antigen Presenting Cells or APC.

It is believed that changes in the number and function of peripheral T-cells are associated with alopecia areata but the studies actually show nothing specific and frequently contradict each other. Most studies report no changes in the number of circulating T-cells and the number of T-helper cells but mention a reduction in the number of suppressor T-cells thus increasing the T-helper/T-suppressor ratio. This ratio tends to become normal in the re-growing phase of alopecia areata. There is neither any consistency in the kind of changes reported in the function of the peripheral T-cells nor any reason given for such changes. Perhaps the studies were flawed.

The dense peribulbar lymphocytic infiltrate surrounding the early anagen follicle bulb is the most common abnormality in alopecia areata. This infiltrate consists mostly of T lymphocytes and to smaller extent macrophages and Langerhan’s cells. As the disease progresses, entry into the matrix and follicular epithelia follows. This infiltrate is seen to precede or accompany active lesions and is prominent in the active phase. During the inactive phase, it subsides and disappears during regrowth. More than 75% T-cells are activated and it is mostly the cytotoxic T-cells which enter the infiltrate. The T helper/T suppressor ratio, which ranges between 2/1 to 4/1 is higher than the normal 1/1 ratio in the unaffected skin. The T helper/T suppressor ratio is the same in affected and unaffected hair follicles and becomes almost normal when treated with topical sensitizers.

From these observations, it was inferred that there is an immune response in the lower half of the hair follicle or the peribular blood vessels. Since the ratio of the cells differ from that in the patient it is inferred that the cell accumulation is selective rather then passive. This, with the fact that the cells are activated suggests that they are actively involved in an immune response. The infiltrates around the unaffected hair follicles implies that it is the infiltrates which cause injury to the hair follicles and are not the result of any injury to the hair follicles

Abnormal presence of class-I and II MHC antigens are observed in hair follicles affected by alopecia areata. Such abnormalities are seen also in the hair bulb and the matrix during the active lesions of the disease. Class I MHC antigens are observed before the formation of the intra bulbar infiltrate and therefore may have a role in the accumulation of T-cells. On the other hand, class II MHC appears in the presence of the infiltrate, indicating a secondary event. Langerhan’s cells also collect in the lesion area, particularly between the matrix and the distal part. According to reports, Langerhan’s cells make up 5% of the epithelial cells in hair follicles with progressive alopecia areata, compared to 1% in stationary lesions or unaffected people.

Such aberrant presence of MHC antigens and Langerhan’s cells, both of which are needed for antigen presentation, in hair bulbs may be responsible for the genesis of auto immune response of self-antigens in hair bulbs. Class I MHC antigens are needed for interaction with cytotoxic T-cells. It is thought that these MHC antigens facilitate damage to hair bulbs by the cytotoxic T-cells. The presence of class II MHC shows that epithelial cells in hair bulbs are damaged.

The autoimmune basis of the disease is shown by the fact that most therapies aim, to reduce the number of lymphocytes or modify their function. These therapies also attempt to suppress the expression of MHC antigens and Langerhan’s cells in order to induce hair regrowth. All this goes to show that suppression or normalization of the infiltrate is beneficial and that the infiltrate is the cause of the disease and not its effect.

The hair bulbs seem to be affected first. In or near the hair bulbs are three types of cells, which may have a certain involvement. These are cortical keratinocytes, melanocytes and endothelial cells. It is unknown which of these is attacked but electron microscopy and other studies indicate that pre-cortical keratinocytes are injured in alopecia areata. Abnormal expression of DR antigens is another indication of keratinocyte damage. Such DR expression is seen only in the presence of lymphocytic infiltrates implying that these infiltrates cause keratinocyte destruction.

Studies show that melanocytes are attacked in alopecia areata. This is indicated by; firstly, the fact that alopecia does not attack white or unpigmented hair and secondly, by whitening of hairs of affected persons during attack. The disease preferentially attacks hair follicles containing melanocytes. The presence of melanophages near the affected bulbs also shows damage to the melanocytes. Melanocytes are perhaps the first cells to be attacked by the macrophages. However, other reports suggest that melanocyte destruction occurs near the necrotic keratinocytes. Since studies are ongoing, nothing definite can be said now.

There is also evidence of endothelial cell involvement in alopecia areata. Damages to these cells occur in the early stages of alopecia areata and their presence in the hair bulb happens later.



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