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Understanding Systemic Lupus Erythematosus Physiopathology in the Light of Primary Immunodeficiencies

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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), immunedysregulation 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.

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.

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Acknowledgment

This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (grant 2002/05880-4 to MC-S) and Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (grants 302469/2005-2 to CAAS and 34802/2005-0 to MC-S).

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Authors and Affiliations

  1. Rheumatology Division, Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Magda Carneiro-Sampaio, Bernadete Lourdes Liphaus, Adriana Almeida Jesus, Clovis Artur A. Silva & Maria Helena Kiss

  2. Immunology Division, Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Magda Carneiro-Sampaio & Maria Helena Kiss

  3. Department of Dermatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    João Bosco Oliveira

  4. Instituto da Criança, Hospital das Clínicas da FMUSP, Av. Dr. Enéas Carvalho Aguiar, 647, 05403-900, São Paulo, SP, Brazil

    Magda Carneiro-Sampaio

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  1. Magda Carneiro-Sampaio
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  2. Bernadete Lourdes Liphaus
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Correspondence to Magda Carneiro-Sampaio.

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Carneiro-Sampaio, M., Liphaus, B.L., Jesus, A.A. et al. Understanding Systemic Lupus Erythematosus Physiopathology in the Light of Primary Immunodeficiencies. J Clin Immunol 28 (Suppl 1), 34–41 (2008). https://doi.org/10.1007/s10875-008-9187-2

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