IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

Lovato, Barbara Hartung; Fogagnolo, Leticia; Souza, Elemir Macedo de; Silva, Larissa Juliana Batista da; Velho, Paulo Eduardo Neves Ferreira; Cintra, Maria Leticia; Teixeira, Fernanda

doi:10.1016/j.abd.2023.02.007

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ORIGINAL ARTICLE • An. Bras. Dermatol. 99 (1) • Jan-Feb 2024 • https://doi.org/10.1016/j.abd.2023.02.007 copy

IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?^☆ ☆ Study conducted at the Faculty of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background:

Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE).

Objective:

To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays.

Methods:

Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems.

Results:

Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116).

Study limitations:

Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years.

Conclusions:

In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

KEYWORDS
Cutaneous lupus erythematosus; Cytokines; IL-17; Immunohistochemistry; Interleukin-1beta; Systemic lupus erythematosus

CLE subtype	ARC-82		SLICC-12
CLE subtype	SLE+ n (%)	SLE-n (%)	SLE+ n (%)	SLE-n (%)
DLE (n = 21)	4(19)	17 (80.9)	4 (19)	17 (80.9)
Mean age, years	31	45	31	45
Sex, Female (%)	100	82.3	100	82.3
Positive ANA (%)	25	0	25	0
Anti-DNA (%)	75	0	75	0
Positive anti-SM (%)	25	0	25	0
SAL (n = 17)	12 (70.5)	5 (29.4)	8 (47.05)	9 (52.9)
Mean age, years	40	40	39	41
Sex, Female (%)	75	100	75	89
Positive ANA (%)	100	60	100	78
Positive anti-DNA (%)	42	0	51	0
Positive anti-SM (%)	17	0	25	0
LT (n = 21)	4 (19.04)	17 (80.9)	4 (19.04)	17 (80.9)
Mean age, years	40	35	39	35
Sex, Female (%)	100	94	100	94
Positive ANA (%)	100	30	100	30
Positive anti-DNA (%)	25	0	25	0
Positive anti-SM (%)	0	0	0	0

ARC-82
	CLE/SLE+ (n = 20)	CLE/SLE-(n = 39)	p-value
IL-1β (epidermal cells), n (%)			0.024
1 (mild)	2 (10)	5 (12.8)
2 (moderate)	2 (10)	16 (41)
3 (intense)	16 (80)	18 (46.2)
IL-1β (interstitial)			<0.05
0	0	3
1 (mild)	3	10
2 (moderate)	16	23
3 (intense)	1	3
IL-17 (epidermal cells)			<0.05
1 (mild)	0	5
2 (moderate)	5	8
3 (intense)	15	26
IL-17 (interstitial)			0.0003
1 (mild)	17 (85)	14 (35.9)
2 (moderate to intense)	3 (15)	25 (64.1)
% of CD56 immunostained cells in 3		0.013
fields (mean±SD)	7.2 ± 3.1	5.6 ± 3.9
% of ICAM immunostained cells in 3		0.0095
fields (mean±SD)	47.5 ±6.7	41.8±7.7
SCLICC
	CLE/SLE+ (n = 16)	CLE/SLE-(n = 43)	p-value
Il-1β (epidermal cells)			0.0143
1 (mild)	0 (0)	7 (16.3)
2 (moderate)	2 (12.5)	16 (37.2)
3 (intense)	14 (87.5)	20 (46.5)
IL-1β (interstitial)			<0.05
1 (mild)	2 (12.5)	14 (32.6)
2 (moderate)	13 (81.3)	26 (60.5)
3 (intense)	1 (6.3)	3 (7)
IL-17 (epidermal cells)			<0.05
1 (mild)	0	0
2 (moderate)	14 (87.5)	33 (76.7)
3 (intense)	2 (12.5)	10 (23.3)
IL-17 (interstitial)			0.0351
1 (mild)	12 (75)	19 (44.2)
2 (moderate to intense)	4 (25)	24 (55.8)

Variable	CLE/SLE+
Variable	P (ARC-82), n = 20	P (SLICC-12), n = 16
Spearman correlation
Perforin and granzyme B correlation	0.0097	0.0148
	CLE/SLE-
Variable	P (ARC-82), n = 39	P (SLICC-12), n =43
Spearman correlation
FoxP3 and granzyme A correlation	0.0257	0.0285
CD8 and granzyme A correlation	0.0075	0.0102
CD8 and granulysin correlation	0.0024	0.0116

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E-mail: revista@sbd.org.br

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[1] ⁎ Corresponding author. E-mail: bhlovato@gmail.com (B.H. Lovato).

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IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?☆ ☆ Study conducted at the Faculty of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil.

Abstract

Background:

Objective:

Methods:

Results:

Study limitations:

Conclusions:

IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?^☆ ☆ Study conducted at the Faculty of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil.