Understanding systemic lupus erythematosus physiopathology in the light of primary immunodeficiencies

Understanding systemic lupus erythematosus physiopathology in the light of primary immunodeficiencies

Author Carneiro-Sampaio, Magda Google Scholar
Liphaus, Bernadete Lourdes Google Scholar
Jesus, Adriana Almeida Google Scholar
Silva, Clovis Artur A. Google Scholar
Oliveira, Joao Bosco Google Scholar
Kiss, Maria Helena Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Introduction Associations between systemic lupus erythematosus (SLE) and primary immunodeficiencies (PIDs) were analyzed to gain insight into the physiopathology of SLE. Some PIDs have been consistently associated with SLE or lupus-like manifestations: (a) homozygous deficiencies of the early components of the classical complement pathway in the following decreasing order: in C1q, 93% of affected patients developed SLE; in C4, 75%; in C1r/s, 57%; and in C2, up to 25%; (b) female carriers of X-linked chronic granulomatous disease allele; and (c) IgA deficiency, present in around 5% of juvenile SLE.Discussion in the first two groups, disturbances of cellular waste-disposal have been proposed as the main mechanisms of pathogenesis. On the other hand and very interestingly, there are PIDs systematically associated with several autoimmune manifestations in which SLE has not been described, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), immunedys-regulation polyendocrinopathy enteropathy X-linked (IPEX), and autoinumme lymphoproliferative syndrome (ALPS), suggesting that mechanisms considered as critical players for induction and maintenance of tolerance to autoantigens, such as (1) AME-mediated thymic negative selection of lymphocytes, (2) Foxp3+ regulatory T cell-mediated peripheral tolerance, and (3) deletion of auto-reactive lymphocytes by Fas-mediated apoptosis, could not be relevant in SLE physiopathology. the non-description of SLE and neither the most characteristic SLE clinical features among patients with agammaglobulinemia are also interesting observations, which reinforce the essential role of B lymphocytes and antibodies for SLE pathogenesis.Conclusion Therefore, monogenic PIDs represent unique and not fully explored human models for unraveling components of the conundrum represented by the physiopathology of SLE, a prototypical polygenic disease.
Keywords systemic lupus erythernatosus
primary immunodeficiencies
complement deficiencies
chronic gramilomatous disease
agammaglobulinemia
APECED
IPEX
ALPS
Language English
Date 2008-05-01
Published in Journal of Clinical Immunology. New York: Springer/plenum Publishers, v. 28, p. S34-S41, 2008.
ISSN 0271-9142 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent S34-S41
Origin http://dx.doi.org/10.1007/s10875-008-9187-2
Access rights Closed access
Type Article
Web of Science ID WOS:000257195600006
URI http://repositorio.unifesp.br/handle/11600/30634

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