The role of Malassezia in the pathogenesis of atopic eczema/dermatitis syndrome
Author: Johansson, Catharina
Date: 2002-02-15
Location: Thoraxklinikens aula, byggnad N2 (Thorax), ingång B, plan U1, Karolinska Sjukhuset
Time: 9.00
Department: Institutionen för medicin / Department of Medicine
Abstract
Atopic eczema/dermatitis syndrome (AEDS) is a chronically relapsing skin
disease, which is often associated with elevated levels of serum lgE. The
immunopathology of AEDS is at present unclear, but it is known that
lymphocytes infiltrating the AEDS lesions are predominantly of the CD4+ T
helper phenotype. Individuals with AEDS often have lgE antibodies to the
yeast Malassezia, earlier denoted Pityrosporum, a member of the normal
cutaneous flora. The aim of this study was to investigate the role of
Malassezia in the pathogenesis of AEDS, particularly with a focus on
T-cell stimulating activity.
Peripheral blood mononuclear cells (PBMC) from AEDS patients with
Malassezia specific serum lgE showed a dose dependent, proliferative
response against Malassezia, which was significantly higher than the
response in PBMC from healthy individuals. Malassezia reactive T-cell
clones were established from the skin and blood of two AEDS patients with
high serum IgE-levels against Malassezia. The majority of the clones were
CD4+, and the skin-derived T-cell clones produced more Th2 cytokines than
the clones derived from blood. Furthermore, Malassezia reactive T-cell
lines could be established both from AEDS patients with Malassezia
specific serum lgE and non-atopic healthy individuals. The T-cell lines
derived from AEDS patients showed a significantly higher production of M
cytokines than those derived from healthy individuals.
To investigate if the T-cell stimulating activity of Malassezia could be
due to components of the yeast having superantigen activity the usage of
T-cell receptor P-chain V-gene segments (TCRBV) was compared in freshly
prepared PBMC and Malassezia reactive T-cell lines from AEDS patients and
healthy controls. It could not be excluded that parts of the T-cell
response against Malassezia are driven by superantigens, but with the
methods available, 1 did not find any evidence for superantigen activity
in extracts of Malassezia. Instead these data support the importance of
classical MHC restricted allergens.
To study the occurrence of reactivity to Malassezia extract and three
recombinant Malassezia allergens (rMal s 1, rMal s 5 and rMal s 6),
measured as specific serum IgE, positive skin prick test (SPT) and atopy
patch test (APT) reactions, 132 adult AEDS patients, selected without
knowledge of their serum lgE levels, were investigated at three Swedish
University Hospitals. Sixty-seven percent of the AEDS patients, but none
of 33 healthy controls, reacted with specific serum lgE, positive SPT
andlor positive APT reaction to any of the tested Malassezia allergens.
Addition of APT to the test battery revealed a previously overlooked
impact of Malassezia-hypersensitivity also in subgroups of AEDS patients
without head and neck dermatitis or without high total serum lgE.
Forty AEDS patients and 16 healthy controls were additionally
investigated for their in vitro PBMC response to Malassezia. The AEDS
patients were subdivided according to their in vivo reaction to
Malassezia extract into three groups: SPT+/APT+ (n=12), SPT+/APT- (n=12),
and SPT- /APT(n=16). The SPT+/APT+ and the SPT+/APT-, but not the
SPT-/APT- patients, had a significantly higher PBMC-proliferation to
Malassezia than the healthy controls. Interestingly, the
PBMCproliferation to Malassezia in the SPT+/APT+ group were significantly
higher than in the SPT+/APT- group. Furthermore, in response to in vitro
Malassezia-stimulation both PBMC proliferation and M cytokine-production
correlated with the APT reactions to Malassezia, strongly suggesting a
relationship between circulating T-cells, with a Th2-like cytokine
profile, and positive APT reactions.
In conclusion, AEDS patients with Malassezia-specific serum IgE, unlike
healthy individuals, have acquired a Th2-like T-cell response to
classical antigens in Malassezia, that may be of importance for
maintaining their skin inflammation. This hypothesis gets further support
in the correlation between in vivo APT reaction and in vitro PBMC
reactivity to Malassezia. The addition of APT and rMaI allergens to the
test battery will improve the possibility to identify AEDS patients with
Malasseziahypersensitivity.
List of papers:
I. Tengvall Linder M, Johansson C, Zargari A, Bengtsson A, van der Ploeg I, Jones I, Harfast B, Scheynius A (1996). "Detection of Pityrosporum orbiculare reactive T cells from skin and blood in atopic dermatitis and characterization of their cytokine profiles. " Clin Exp Allergy 26(11): 1286-97
Pubmed
II. Tengvall Linder M, Johansson C, Bengtsson A, Holm L, Harfast B, Scheynius A (1998). "Pityrosporum orbiculare-reactive T-cell lines in atopic dermatitis patients and healthy individuals. " Scand J Immunol 47(2): 152-8
Pubmed
III. Johansson C, Jeddi-Tehrani M, Grunewald J, Tengvall Linder M, Bengtsson A, Hallden G, Scheynius A (1999). "Peripheral blood T-cell receptor beta-chain V-repertoire in atopic dermatitis patients after in vitro exposure to Pityrosporum orbiculare extract. " Scand J Immunol 49(3): 293-301
Pubmed
IV. Johansson C, Sandstrom MH, Bartosik J, Sarnhult T, Christiansen J, Zargari A, Back O, Wahlgren CF, Faergemann J, Scheynius A, Tengvall-Linder M (2002). "Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients." (Submitted)
V. Johansson C, Eshaghi H, Tengvall-Linder M, Jakobson E, Scheynius A (2002). "Positive atopy patch test reaction to Malassezia furfur in atopic dermatitis correlates with a Th2 like PBMC response." J Invest Dermatol (In Print)
I. Tengvall Linder M, Johansson C, Zargari A, Bengtsson A, van der Ploeg I, Jones I, Harfast B, Scheynius A (1996). "Detection of Pityrosporum orbiculare reactive T cells from skin and blood in atopic dermatitis and characterization of their cytokine profiles. " Clin Exp Allergy 26(11): 1286-97
Pubmed
II. Tengvall Linder M, Johansson C, Bengtsson A, Holm L, Harfast B, Scheynius A (1998). "Pityrosporum orbiculare-reactive T-cell lines in atopic dermatitis patients and healthy individuals. " Scand J Immunol 47(2): 152-8
Pubmed
III. Johansson C, Jeddi-Tehrani M, Grunewald J, Tengvall Linder M, Bengtsson A, Hallden G, Scheynius A (1999). "Peripheral blood T-cell receptor beta-chain V-repertoire in atopic dermatitis patients after in vitro exposure to Pityrosporum orbiculare extract. " Scand J Immunol 49(3): 293-301
Pubmed
IV. Johansson C, Sandstrom MH, Bartosik J, Sarnhult T, Christiansen J, Zargari A, Back O, Wahlgren CF, Faergemann J, Scheynius A, Tengvall-Linder M (2002). "Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients." (Submitted)
V. Johansson C, Eshaghi H, Tengvall-Linder M, Jakobson E, Scheynius A (2002). "Positive atopy patch test reaction to Malassezia furfur in atopic dermatitis correlates with a Th2 like PBMC response." J Invest Dermatol (In Print)
Issue date: 2002-01-25
Publication year: 2002
ISBN: 91-7349-127-6
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