title: Understanding systemic lupus erythematosus physiopathology in the light of primary immunodeficiencies.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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), immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX), and autoimmune lymphoproliferative syndrome (ALPS), suggesting that mechanisms considered as critical players for induction and maintenance of tolerance to autoantigens, such as (1) AIRE-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Rheumatology Division, Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. magdascs@icr.hcnet.usp.br
authors.forename: Magda
authors.initials: M
authors.lastname: Carneiro-Sampaio
authors.forename: Bernadete Lourdes
authors.initials: BL
authors.lastname: Liphaus
authors.forename: Adriana Almeida
authors.initials: AA
authors.lastname: Jesus
authors.forename: Clovis Artur A
authors.initials: CA
authors.lastname: Silva
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Oliveira
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Kiss
mesh_terms: D000818:Animals; D015551:Autoimmunity; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000172:deficiency / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D011110:Polymorphism, Genetic; D017634:Self Tolerance; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D000096927:AIRE Protein
chemical_list: D023201:CD40 Ligand; D003165:Complement System Proteins; D051858:Forkhead Transcription Factors; D007136:Immunoglobulins; D014157:Transcription Factors; D000096927:AIRE Protein; C418974:FOXP3 protein, human