One mechanism by which alopecia areata might occur

Alopecia areata hair loss information for men and women
Alopecia Areata 
Alopecia Areata Biology
Alopecia Areata Treatments

  Proposed Mechanism of Alopecia Areata
 
Alopecia areata is a hair loss disorder that primarily affects the hair follicle as it enters the prolonged growth phase called anagen. It is characterized by a sudden onset of, typically, circumscribed bald patches, that may increase in numbers and coalesce to form extensive alopecia areata. None of the treatments is curative, aiming, as they do, at suppressing the symptoms. Proposed mechanisms have ranged from hormonal disruption and infection to stress and toxins.

It was in the late 1950s that an autoimmune mechanism was proposed for alopecia areata. Since then, enough circumstantial evidence has accumulated to support such a proposition. The current view is that alopecia areata is an autoimmune disease but definite proof is lacking. Research on alopecia areata is now focused on mainly two areas – the role of the immune system and the nature of hair follicle pathology.

In an autoimmune disease, primarily four conditions have to be met:

  1. Presence of unique antigens in the affected organ.
  2. An autoimmune response to that antigen.
  3. An autoimmune response specifically associated with the disease.
  4. The autoimmune response producing the disease and not following it.

Though alopecia areata does not meet all these conditions, indirect evidence of alopecia areata as an autoimmune disease is its association with a particular class-II HLA hapolotype, association of the disease with two autoimmune diseases viz. atopy and Downs syndrome and a similar response to immuno suppressive therapies. In addition, alopecia areata shares with other autoimmune diseases similar morphological features.

Studies indicate that alopecia areata, is most likely to attack the hair bulb. In and around the hair bulb are three cell types, which may be involved, in the autoimmune attack. They are cortical keratinocytes-epidermal cells that produce keratins, melanocytes – epidermal cells that synthesize melanin, and endothelial cells. It is not known, which are attacked but the stem cells, which supply new cells to the follicles, it seems are spared, since the hairs always have the potential to regrow and do regrow.

Alopecia areata attacks the hair follicle in the anagen phase. The initial event in the disease is the premature entry of the anagen follicle into the rest or telogen state, bypassing the intermediate catagen regression state. The follicles then enter the next growth stage but due to the disease, produce poor aberrant fibers. Some say, that this two-stage aberrant cycle continues while others say the fiber eventually is arrested in the telogen state. Whatever the truth, eventually hair shedding occurs.

Others have developed the ‘Sequestered Antigen Mechanism’ concept. Sequestered antigens are antigens, which the immune system cannot identify. Here it is proposed that such antigens, normally hidden in the follicle are released due to injury. There is a class of proteins called Major Histocompatibility Proteins or MHC, which present the invading antigens to the immune cells. Without these proteins, the immune system is useless. Normally there is a low expression of MHC in follicles. If, due to injury or any event, these sequestered antigens are released, the expression of MHC in follicles increases, resulting in attack on the body’s own antigens. It is believed that some alopecia areata patients could be genetically predisposed to abnormal MHC expression.

The immune system is normally well equipped to detect and destroy any foreign body. It recognizes the body’s own cells with the help of an antigen called human leukocyte antigen or HLA. They are called self-antigens. Autoimmune disorder occurs when a foreign antigen mimics the body’s own antigen. The immune system in attacking these foreign antigens ends up destroying the body’s antigens also.

The immune system uses three types of, what is called, T-cells. These are killer, helper and suppressor T-cells. The killer T-cell actually destroys the foreign body. Normally such cells are not present in healthy skins. However, T-cells are present in scalp skins affected by alopecia areata. Some say the T-cells attack the hair follicle in the anagen phase causing the hair to stop growing and enter the telogen phase. After a period, this hair is shed. There is regrowth only when the T-cells stop attacking the hair.

Proposed Mechanism of Alopecia Areata

All the data available suggest that alopecia areata is an autoimmune disorder but does not conclusively prove it. Successful demonstration of specific T-cell response to hair follicle antigen has so far eluded researchers. The following proposition tries to link and satisfactorily explain the data and immunological abnormalities observed in the course of several studies.

Alopecia could be an auto immune response involving T-cells and antibodies, directed specifically to self-antigens in keratinocytes and, or, melanocytes in the hair bulbs. Bringing about this auto immune response would be made easier by:

  • A reduction in the number of suppressor T-cells.
  • A reduction in the T-helper/ T-suppressor ratio in circulation.
  • An abnormal expression of Langerhan’s cells and MHC class I antigens in the cortex and matrix of hair bulbs.

The resulting immune responses would induce an immunoglobin deposit around hair bulbs and in the infiltrates of hair bulbs containing immune cells. The increased presence of class-I antigens on hair bulb cells would make it easier for the killer T-cells to attack and injure them.

If the injury is mild, there would be an expression of class-II MHC antigens on the injured cells leading to stoppage of any further maturation of hair fiber cells. The hair fibers would enter catagen, leading to clinical hair loss. If the injury is severe it would lead to histologic evidence of cell death.

This proposition is based on the assumption that keratinocytes and melanocytes in the hair are different, qualitatively and/or quantitatively, from similar cells in other regions of the epidermis, in their antigenic properties, leading to a preferential attack on them. The proof of this is the unique expression of antigens in hair follicles, which are not found in the epidermis and dermis. Since, in alopecia areata, matrix cells are selectively attacked during the increased mitotic activity in anagen, it is possible that the related antigens are separation antigens of keratinocyte and melanocytes.

The abnormal immunoglobin deposits in hair fiber, which are related to the hair cycle and similar deposits seen in male alopecia patterns raises the interesting possibility that immune factors, by causing entry into catagen, may be involved in regulating the normal hair cycle.



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