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What
is autoimmunity ?
AA is widely believed to be an autoimmune disease. A breakdown
in the immune system results in autoimmunity. Essentially every
individual produces various cell types that fight disease and infection.
There are all sorts of immune cells such as lymphocytes, monocytes,
macrophages and other cells, all of which have different roles to
play in fighting off infection. To fight invading organisms the
immune cells must be able to recognize bacteria (or whatever) as
foreign and not part of the individual's own body. They do this
by recognizing structures called antigens (antigens are usually
proteins) on the surface of the invader. Every individual organism,
including our ourselves, has a different set of antigens and the
immune system as a whole can recognize all antigens with different
immune cell clones/types recognizing different antigens.
Potentially the immune system can recognise any antigen on any
bacteria, cell, or whatever, whether it is foreign or part of our
own body. Those particular immune cells in our bodies that react
with our own antigens must be prevented from coming into contact
with the antigens or have their activity prohibited to stop them
attacking and destroying our own organs. For the most part, prohibition
of self reactive cells or prevention of contact with self antigens
is done successfully, but inevitably within the complexities of
the immune system things can go wrong. The development of an autoimmune
disease can occur when potentially autoreactive cells escape our
bodies' mechanisms of rendering them ineffective. The lymphocytes
go to work with potentially catastrophic results on the organs where
the antigens they are specific for are expressed.
The cause of the initiation of alopecia areata is not known
but there is apparently a destructive response, mainly from lymphocytes
and macrophages, to certain antigens in the hair follicle. There
are several general hypotheses to explain the initiation of autoimmune
diseases and just how our autoreactive cells become dangerous
and
destroy our own tissues. The main ones are described in more detail
in the Immunology
section of this web site.
  
The identity parade. Electron Microscope photographs
of an antibody producing B cell, a macrophage and a lymphocyte.
Normally good things to have but one or more of these cell types
can be the perpetrators of autoimmune disease. Click pictures for
larger views.
When
autoimmune disease occurs in other organs the tissue is entirely
destroyed. Why does this not happen in alopecia areata ?
When skin biopsies are examined alopecia areata affected hair
follicles can often be seen to be still quite active. They are in
a state called dystrophic anagen where follicles are producing root
sheath material and often hair fibers - but they are too small and
aberrant to protrude above the skin epidermis. White blood cells
can be seen clustered in and around the hair follicle bulb and are
presumably causing the disruption. However, there is no permanent
destruction, under the right conditions the hair follicles can regrow
normal hair. So this is an intriguing twist to classic autoimmune
disease theory. In most autoimmune diseases the relevant organ(s)
are attacked and eventually destroyed by the immune system. In alopecia
areata the hair follicles are just disrupted and prohibited from
producing hair.
Although most clinicians are convinced that autoimmunity is the
root cause of alopecia areata, the classical interpretation of autoimmunity
in this case is open to question. The immune system may be involved
in inhibiting hair production via cell mediated activity, but considering
there is a lack of total tissue destruction in alopecia areata,
immune cells could be exerting their effects by more subtle means.
For example, it has been suggested that the immune system is directed
against a controlling hair growth promoter mechanism rather than
actual hair follicle tissue (Price 1991, Rook 1991). Some investigators
have suggested cytokines (chemical signals made by cells) produced
by immune cells and hair follicles themselves may adversely affect
the hair follicle (Goldsmith 1991). Or perhaps the antigen exists,
or is exposed, for only a short time at the initiation of alopecia
areata and thereafter alopecia areata is perpetuated by an imbalance
in the immune system.
The most popular current hypothesis is that the hair follicles
may drop out of their hair producing state into a telogen resting
phase. This would mean the hair follicles would not express as many
antigens and so antigenic stimulation of the immune cells would
be reduced/removed. The immune cells would then disperse until the
hair follicle reverted back to its active anagen state when the
immune cells would return (McDonagh 1994). By running through this
repeated cycle of events, or by remaining in telogen, the hair follicle
could avoid the worst of the tissue destruction. Of course more
than one of the above mechanisms may be in operation.
Is
autoimmunity the most important cause of hair loss in alopecia areata
?
Many journal reports introduce the subject with a phrase along
the lines of "the etiology of alopecia areata is entirely unknown"
(eg Price 1991, Perret 1984, Paus 1993). Indirect evidence points
towards hair loss being a result of immune system activity - an
autoimmune disease. The evidence primarily consists of observation
of an immune cell infiltrate in and around dystrophic hair follicles
and the knowledge that some people with alopecia areata can regrow
hair when undergoing immunosuppressive therapy (eg Gupta 1990).
Further evidence comes from the association of alopecia areata with
other autoimmune diseases. However, a small minority of dermatologists
reject the idea of alopecia areata being an autoimmune disease.
Indirect evidence provided in support of an autoimmune mechanism
is not incontrovertible. There are many theoretically possible,
pathogenic pathways that may elicit hair loss in alopecia areata
and lead to expression of an immune cell infiltrate. They can be
classed into three main groups: 1) Third factor activity
- the development of hair loss and the immune cell infiltrate in
and around hair follicles is not because of interaction between
the two. Rather, a third factor such as infection induces both hair
loss and the immune response. 2) Autoimmunity induces disease
- abnormal presentation of self and/or cross reactive antigens to
the immune system evokes an immune cell infiltrate as a "first line
of defence" and primary trigger for the onset of alopecia areata.
In other words, the immune system is acting abnormally against a
normally functioning hair follicle. 3) Disease induces autoimmunity
- hair follicle tissue damage or abnormal follicle activity may
result in exposure of self antigens to the immune system. Or expression
of non-self antigens on hair follicle cells, as would occur if they
were virally infected, may precipitate an immune response to the
non-self antigen which also adversely affects surrounding tissues.
In other words, the immune system is acting normally against an
abnormally functioning hair follicle.
We need evidence to support or refute these three possibilities.
What precipitates the infiltrate of immune cells in and around hair
follicles in the first place is unknown. In classic autoimmunity
the initiation would be attributed to autoreactive antigens situated
in the hair follicle which would be attacked by the immune system.
But so far suspect antigens that should be present in the hair follicles
of alopecia areata patients have not been identified and the mechanism
by which hair loss is induced is not known.
Alopecia
areata and autoimmune disease references
- McElwee
KJ, Tobin DJ, Bystryn JC, King LE Jr, Sundberg JP. Alopecia areata:
an autoimmune disease? Exp Dermatol. 1999 Oct;8(5):371-9.
- Colombe
BW, Lou CD, Price VH. The genetic basis of alopecia areata: HLA
associations with patchy alopecia areata versus alopecia totalis
and alopecia universalis. J Investig Dermatol Symp Proc. 1999
Dec;4(3):216-9.
- Cork MJ,
Crane AM, Duff GW. Genetic control of cytokines. Cytokine gene
polymorphisms in alopecia areata. Dermatol Clin. 1996 Oct;14(4):671-8.
- Paus R,
Slominski A, Czarnetzki BM. Is alopecia areata an autoimmune-response
against melanogenesis-related proteins, exposed by abnormal MHC
class I expression in the anagen hair bulb? Yale J Biol Med. 1993
Nov-Dec;66(6):541-54.
- Westgate
GE, Craggs RI, Gibson WT. Immune privilege in hair growth. J Invest
Dermatol. 1991 Sep;97(3):417-20.
- Khoury
EL, Price VH, Greenspan JS. HLA-DR expression by hair follicle
keratinocytes in alopecia areata: evidence that it is secondary
to the lymphoid infiltration. J Invest Dermatol. 1988 Feb;90(2):193-200.
- Brocker
EB, Echternacht-Happle K, Hamm H, Happle R. Abnormal expression
of class I and class II major histocompatibility antigens in alopecia
areata: modulation by topical immunotherapy. J Invest Dermatol.
1987 May;88(5):564-8.
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AG, Bleehen SS. Expression of HLA-DR by anagen hair follicles
in alopecia areata. J Invest Dermatol. 1985 Dec;85(6):569-72.
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In: Bos JD, ed. Skin immune system (SIS) Cutaneous immunology
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press, 1997: 377-398.
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analysis of T-cell subsets in the peribulbar and intrabulbar infiltrates
of alopecia areata. Acta Derm Venerol 1984; 64: 26-30.
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