Common Variable Immunodeficiency in Systemic Lupus Erythematosus

doi:10.1016/j.semarthrit.2006.09.005

Seminars in Arthritis and Rheumatism

Volume 36, Issue 4, February 2007, Pages 238-245

https://doi.org/10.1016/j.semarthrit.2006.09.005 Get rights and content

Objective

The development of common variable immunodeficiency (CVID) or hypogammaglobulinemia in systemic lupus erythematosus (SLE) is rare. The purpose of this article is to provide a detailed review of lupus-associated CVID and to identify clinical characteristics and laboratory features in patients with SLE-associated CVID.

Methods

We describe 2 patients with SLE and CVID and review the cases published in the English literature highlighting both the demographic and the clinical characteristics and the laboratory and therapeutic aspects of this disorder.

Results

Detailed descriptions of 18 patients were available; 89% were females with a mean age at the onset of SLE of 23.8 years. In 50% of patients CVID developed within the first 5 years after the diagnosis of SLE. All patients had been treated with corticosteroids and 72% had also received immunosuppressive therapy. Sinopulmonary infections were the most frequent symptom. SLE disease activity decreased after the development of CVID in 67% of patients. Most patients (89%) were treated with gammaglobulin therapy. The most notable immunological feature was a reduced number or percentage of B-cells in 60% of patients.

Conclusions

CVID should be suspected in any SLE patient with recurrent sinopulmonary infections in the absence of SLE activity and/or immunosuppressive treatment.

Section snippets

Literature Review

A review of the published literature using a search of the entire PubMed database made available by the National Library of Medicine was undertaken. The search included articles from 1982 to 2005. Key articles on SLE and hypogammaglobulinemia were identified, and additional articles of interest were selected from the bibliographies of the published literature.

Flow Cytometry Analysis

Flow cytometry analysis to identify lymphocyte subsets was performed in our 2 SLE patients with CVID and 38 SLE patients without CVID.

Case 1

In June 2002, an 18-year-old white woman was admitted to our hospital with the diagnosis of epilepsy and SLE, characterized by malar rash, serositis, fever, abdominal pain, and hemolytic anemia with a positive Coombs test. Symptoms were controlled with intravenous (IV) high doses of methylprednisolone. After discharge, she was treated with prednisone (20 mg/d) and azathioprine (50 mg/12 h). Despite this treatment, her disease remained active, with malar rash, diffuse alopecia, and

Flow cytometry analysis

Lymphocyte subsets in these 2 patients were compared with the percentage of these cells in 38 patients with SLE without CVID. No differences in the percentage of CD3+CD4+, CD3+CD8+ cells nor in the CD4/CD8 ratio were observed. The main differences found were that both patients had a lower percentage of natural killer cells (4 and 5%, respectively, in contrast with 14% in SLE patients without CVID) and an almost absent number of B-cells (≤1%), as shown in Table 1 and Fig. 1.

Literature review

During the last 24 years (1982 to 2006) detailed descriptions of 16 SLE patients with CVID were reported in 10 articles in the English literature (1, 2, 3, 4, 5, 6, 7, 8, 9, 10). These patients, together with the 2 described above, are included in this review (Table 2). It is difficult to estimate the prevalence and incidence of CVID in SLE from case reports and small series.

Sixteen patients of the 18 included in this review were women (89%), with a mean age at onset of SLE of 23.8 years (range

Discussion

Excluding selective IgA deficiency, CVID is recognized as the most prevalent primary immunodeficiency disease. Search of English medical literature identified detailed descriptions of 16 SLE patients with CVID (1, 2, 3, 4, 5, 6, 7, 8, 9, 10). It is clear that definite conclusions cannot be drawn from such a review of individual cases. In addition, details were occasionally missing from some of the cases in the literature. Nevertheless, some valuable information and practical points can be

Acknowledgment

Susana Mellor-Pita is funded by the Instituto de Salud Carlos III (N CM04/00161).

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Common variable immunodeficiency (CVID) is a primary immunodeficiency that is clinically heterogeneous, characterized by both infectious and noninfectious complications. Although the hallmark of disease presentation is commonly a history of recurrent sinopulmonary infections, autoimmunity and noninfectious inflammatory conditions are increasingly associated with CVID.
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Systemic lupus erythematosus (SLE) is a multisystemic disease with a variety of clinical presentations. Monogenic predisposing conditions to the development of this disease have been described. As examples, an impaired expression of interferon-α regulated genes or complement deficiencies have been reported in patients with SLE, with particular clinical presentations. Those defects present particular presentations and a different severity, making an argument that lupus is not a single disease but many. Treatment could be individualized depending on the underlying defect generating the subtype of the disease.
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Fernandez-Castro et al. described a series of 18 patients with SLE and CVID. Interestingly, up to 67% of them had the autoimmune disease controlled after the development of the immunodeficiency.26 Genetic abnormalities described in CVID include defects in the inducible co-stimulator (ICOS), the membrane activator and calcium-modulator interactor (TACI), the B-cell activating factor receptor (BAFF-R), CD19, CD20 and CD81 (Table 2).19
Primary immunodeficiency disorders (PID) represent a heterogeneous group of diseases resulting from inherited defects in the development, maturation and normal function of immune cells; thus, turning individuals susceptible to recurrent infections, allergy, autoimmunity, and malignancies. In this retrospective study, autoimmune diseases (AIDs), in special systemic lupus erythematosus (SLE) which arose associated to the course of PID, are described. Classically, the literature describes three groups of PID associated with SLE: (1) deficiency of Complement pathway components, (2) defects in immunoglobulin synthesis, and (3) chronic granulomatous disease (CGD). Currently, other PID have been described with clinical manifestation of SLE, such as Wiskott–Aldrich syndrome (WAS), autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), autoimmune lymphoproliferative syndrome (ALPS) and idiopathic CD4⁺ lymphocytopenia. Also we present findings from an adult cohort from the outpatient clinic of the Rheumatology Division of Universidade Federal de São Paulo. The PID manifestations found by our study group were considered mild in terms of severity of infections and mortality in early life. Thus, it is possible that some immunodeficiency states are compatible with survival regarding infectious susceptibility; however these states might represent a strong predisposing factor for the development of immune disorders like those observed in SLE.
As imunodeficiências primárias (IDP) representam um grupo heterogêneo de doenças resultantes de defeitos hereditários no desenvolvimento, maturação e função normal de células do sistema imunológico; assim, tornam os indivíduos suscetíveis a infecções recorrentes, alergia, autoimunidade e doenças malignas. Neste estudo retrospectivo, descrevem-se doenças autoimunes (DAI), em especial o lúpus eritematoso sistêmico (LES), que surgiram associadas ao curso das IDP. Classicamente, a literatura descreve três grupos de IDP associadas ao LES: (1) deficiência de componentes da via do complemento, (2) defeitos na síntese de imunoglobulinas e (3) doença granulomatosa crônica (DGC). Na atualidade, outras IDP têm sido descritas como manifestações clínicas do LES, como a síndrome de Wiskott–Aldrich (WAS), a poliendocrinopatia autoimune-candidíase-distrofia ectodérmica (APECED), a síndrome linfoproliferativa autoimune (ALPS) e a linfocitopenia idiopática CD4⁺. Também são apresentados achados de uma coorte de adultos do ambulatório da Divisão de Reumatologia da Universidade Federal de São Paulo. As manifestações de IDP encontradas pelo nosso grupo de estudo foram consideradas leves em termos de gravidade de infecções e mortalidade no início da vida. Assim, é possível que alguns estados de imunodeficiência sejam compatíveis com a sobrevivência em relação à suscetibilidade infecciosa; no entanto, estes estados podem representar um fator de predisposição forte para o desenvolvimento de doenças imunológicas, como observado no LES.

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: The authors have no conflicts of interest to disclose.

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Common Variable Immunodeficiency in Systemic Lupus Erythematosus

Objective

Methods

Results

Conclusions

Section snippets

Literature Review

Flow Cytometry Analysis

Case 1

Flow cytometry analysis

Literature review

Discussion

Acknowledgment

J Allergy Clin Immunol

J Allergy Clin Immmunol

Am J Med

Am J Med

Clin Immunol

Clin Immunol

Am J Med

Cell Immunol

Common variable immunodeficiency in a patient with systemic lupus erythematosus

Lupus

Concurrent systemic lupus erythematosus and common variable hypogammaglobulinemia

Arthritis Rheum

Immunoglobulin deficiency in patients with systemic lupus erythematosus

Clin Exp Rheumatol

Hypogammaglobulinemia in systemic lupus erythematosus: report of a case with evidence for spontaneously activated T suppressor cells

Clin Exp Rheumatol