Scleroderma Peripheral B Lymphocytes Secrete Interleukin-6 and Transforming Growth Factor ß and Activate Fibroblasts.
Arthritis Rheumatol
; 69(5): 1078-1089, 2017 05.
Article
em En
| MEDLINE
| ID: mdl-27992693
ABSTRACT
OBJECTIVE:
To study the role of B lymphocytes in systemic sclerosis (SSc).METHODS:
Peripheral B cell subpopulations and the production of interleukin-6 (IL-6) and transforming growth factor ß (TGFß) were analyzed using flow cytometry and multiplex assay. The fibroblast proliferation rate upon incubation with supernatants from B cells isolated from SSc patients or healthy controls was assessed using XTT, bromodeoxyuridine, and Ki-67. Collagen production was assessed using a collagen assay.RESULTS:
Ninety untreated patients (12 males) fulfilling the American College of Rheumatology/European League Against Rheumatism criteria for SSc (23 with diffuse cutaneous SSc [dcSSc] and 67 with limited cutaneous SSc [lcSSc]) and 30 healthy controls were recruited. Increased proportions of B cells expressing CD69 and CD95 were identified among the patients with SSc. B lymphocytes from dcSSc patients versus lcSSc patients and healthy controls expressed increased proportion of cells positive for CD5 (mean ± SD 24.12 ± 7.93% versus 14.09 ± 6.58% [P = 0.03] and 14.21 ± 5.34% [P = 0.01]), CD86 (39.89 ± 22.11% versus 17.72 ± 13.98% [P = 0.0007] and 11.68 ± 11.09% [P < 0.001]), IL-6 receptor (IL-6R; 33.64 ± 23.12% versus 17.91 ± 13.62% [P < 0.0001] and 12.08 ± 8.68% [P = 0.0009]), or IL-21R (32.55 ± 20.19% versus 5.76 ± 4.40% [P < 0.0001] and 5.93 ± 3.29% [P < 0.0001]). In addition, the levels of IL-6 (mean ± SD 314.3 ± 317.8 pg/ml versus 6.10 ± 2.58 pg/ml; P = 0.0007) and TGFß (mean ± SD 1,020 ± 569 pg/ml versus 163.8 ± 98.69 pg/ml; P = 0.001) secreted by B lymphocytes from patients with SSc were increased compared to healthy controls. Fibroblast proliferation and collagen production were also significantly increased in the presence of B cell supernatant from SSc patients as compared to healthy controls.CONCLUSION:
The numbers of activated B cells were increased in SSc patients, and the up-regulation of CD5, CD86, IL-6R, and IL-21R discriminated between patients with dcSSc and those with lcSSc. Peripheral B lymphocytes from SSc patients secreted both IL-6 and TGFß, and they activated fibroblasts in vitro.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Fator de Crescimento Transformador beta
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Colágeno
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Interleucina-6
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Esclerodermia Difusa
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Esclerodermia Limitada
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Proliferação de Células
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Fibroblastos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Arthritis Rheumatol
Ano de publicação:
2017
Tipo de documento:
Article