Plasmablasts With a Mucosal Phenotype Contribute to Plasmacytosis in Systemic Lupus Erythematosus.
Arthritis Rheumatol
; 69(10): 2018-2028, 2017 10.
Article
em En
| MEDLINE
| ID: mdl-28622453
ABSTRACT
OBJECTIVE:
To analyze the composition of known plasmacytosis in systemic lupus erythematosus (SLE) to obtain further insight into the nature of underlying mechanisms.METHODS:
Plasmablasts from patients with active SLE, patients with inactive/treated SLE, and healthy controls were characterized by flow cytometry, enzyme-linked immunospot assay, and Transwell migration assays and compared to vaccination-induced plasmablasts. Serum cytokine levels were analyzed by Luminex assay, and histologic analysis of kidney biopsy specimens was performed.RESULTS:
Circulating plasmablasts in SLE expressed markers of mucosal immune reactions. IgA, CCR10, and ß7 integrin were expressed by 48%, 40%, and 38% of plasmablasts, respectively, with varying coexpression patterns. Consistent with mucosal homing, some SLE plasmablasts migrated toward the mucosal chemokine CCL28 and secreted polymeric IgA. SLE plasmablasts shared phenotypic characteristics with antigen-specific plasmablasts induced by oral, but not parenteral, vaccinations. Autoreactive antibody-secreting cells of the IgG and IgA isotypes were detectable, but only the emergence of phenotypically mucosal plasmablasts was positively associated with serum interleukin-2 and platelet-derived growth factor BB levels.CONCLUSION:
Our data suggest that distinct plasmablast differentiation pathways jointly contribute to peripheral plasmacytosis in SLE, i.e., a cytokine-amplified mucosal "steady-state" plasmablast response, and an autoreactive plasmablast response, representing conventional autoimmunity. Our results indicate an overly activated mucosal immune system in patients with SLE, with both immunologic and clinical implications.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Plasmócitos
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Autoanticorpos
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Nefrite Lúpica
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Citocinas
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Células Precursoras de Linfócitos B
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Rim
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Lúpus Eritematoso Sistêmico
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Mucosa
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Arthritis Rheumatol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Alemanha