Primary immunodeficiency association with systemic lupus erythematosus: review of literature and lessons learned by the Rheumatology Division of a tertiary university hospital at São Paulo, Brazil

Errante, Paolo Ruggero; Perazzio, Sandro Félix; Frazão, Josias Brito; Silva, Neusa Pereira da; Andrade, Luis Eduardo Coelho

doi:10.1016/j.rbr.2015.03.002

Acessibilidade / Reportar erro

Brasil

Revista Brasileira de Reumatologia

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Review article • Rev. Bras. Reumatol. 56 (1) • Jan-Feb 2016 • https://doi.org/10.1016/j.rbr.2015.03.002 copy

Primary immunodeficiency association with systemic lupus erythematosus: review of literature and lessons learned by the Rheumatology Division of a tertiary university hospital at São Paulo, Brazil

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

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.

Keywords:
Autoimmune disease; Primary immunodeficiency; Systemic lupus erythematosus; Antibodies deficiency

Disease	Association features and autoimmune manifestation	Inheritance	Defective gene	OMIM number
C1q deficiency	SLE-like syndrome, rheumatoid syndrome, infections	AR	C 1QA C1QB C1QC	120550 601269 120575
C1r deficiency	SLE-like syndrome, rheumatoid syndrome, multiple autoimmune diseases, infections	AR	C1r	216950
C1s deficiency	SLE-like syndrome; multiple autoimmune diseases	AR	C1s	120580
C4 deficiency	SLE-like syndrome, rheumatoid syndrome, infections	AR	C 4 A	120810
C2 deficiency	SLE-like syndrome, vasculitis, atherosclerosis, polymyositis, pyogenic infections; glomerulonephritis	AR	C 2	217000
C3 deficiency	Life threatening pyogenic infections; SLE-like disease; glomerulonephritis; atypical hemolytic–uremic syndrome	AR	C 3	120700
C5 deficiency	Neisseria infection, SLE	AR	C 5α or C 5β	120900
C6 deficiency	Neisseria infection, SLE	AR	C 6	217050
C7 deficiency	Neisseria infection, SLE, vasculitis	AR	C 7	217070
C8a deficiency	Neisseria infection, SLE	AR	C 8α	120950
C8b deficiency	Neisseria infection, SLE	AR	C 8β	120960
Factor I deficiency	Recurrent pyogenic infections, glomerulonephritis, SLE; hemolytic–uremic syndrome; severe pre-eclampsia	AR	CFI	610984

	Disease	Association features and autoimmune manifestation	Inheritance	Defective gene	OMIM number
Predominantly antibody deficiencies
	CVID	Hypogammaglobulinemia, recurrent chronic infections, inflammatory bowel disease, autoimmune hemolytic anemia, thrombocytopenia, rheumatoid arthritis, pernicious anemia, diabetes mellitus, polymyositis, SLE	AR AR AR AR AD, AR AR	ICOS CD 19 CD 81 CD 20 TNFRSF 13 B (TACI) TNFRSF 13 C (FABF‐R)	604558 107265 186845 112210 604907 606269
	SIgAD	Usually asymptomatic; may have recurrent infections with poor antibody responses to carbohydrate antigens, rheumatoid arthritis, diabetes mellitus, SLE	Variable	Unknown
	HIGM	Decreased IgG, normal to elevated IgM, sinopulmonary infections, lymphoid hyperplasia, diabetes mellitus, autoimmune hepatitis, rheumatoid arthritis, inflammatory bowel disease, uveitis, idiopathic thrombocytopenia purpura, autoimmune hemolytic anemia, SLE	XL AR AR AR	CD 40 LG CD40 AICDA UNG	300386 109535 605257 191525
	Isolated IgG subclass deficiency	Reduction in one or more IgG subclass, usually asymptomatic; a minority may have poor antibody response to specific antigens and recurrent viral/bacterial infections	Variable	Unknown
	SIgMD ^a a Non-classic PID.	Recurrent respiratory tract infections, asthma, allergic rhinitis, vasomotor rhinitis, angioedema, and anaphylaxis, glomerulonephritis, SLE		Unknown

Congenital defects of phagocyte number, function or both
	CGD	Recurrent suppurative microbial infections, chronic inflammation with granuloma formation, inflammatory bowel disease, SLE	XL AR AR AR AR	CYBB CYBA NCF 1 NCF 2 NCF 4	306400 233690 233700 233710 601488

Well-defined syndromes with immunodeficiency
	WAS	Thrombocytopenia with bleeding diathesis, eczema, recurrent infections, autoimmune hemolytic anemia, vasculitis, inflammatory bowel disease, glomerulonephritis, rheumatoid arthritis, SLE	XL	WAS	301000

Syndromes with autoimmunity
	APECED	Autoimmunity of parathyroid, adrenal, and other endocrine organs, chronic candidiasis, vitiligo, hepatitis autoimmune, diabetes mellitus	AR	AIRE	240300
	ALPS-FAS	Splenomegaly, adenopathies, autoimmune cytopenias, lymphoma, defective lymphocyte apoptosis	AD, AR	TNFRSF 6	601859
	ALPS-FASLG	Splenomegaly, adenopathies, autoimmune cytopenias, defective lymphocyte apoptosis	AD, AR	TNFSF 6	134638
	ALPS-CASP10	Adenopathies, splenomegaly, autoimmunity, defective lymphocyte apoptosis	AD	CASP 10	603909
	Caspase 8 defect	Adenopathies, splenomegaly, recurrent bacterial/viral infections, defective lymphocyte apoptosis, hypogammaglobulinemia	AD	NRAS	164790

Others
	ICL ^a a Non-classic PID.	CD4⁺ lymphocytopenia, opportunistic infections, antiphospholipid syndrome, psoriasis, Hashimoto's thyroiditis, Graves disease, ulcerative colitis, vitiligo and SLE		UNC119

Sociedade Brasileira de Reumatologia Av Brigadeiro Luiz Antonio, 2466 - Cj 93., 01402-000 São Paulo - SP, Tel./Fax: 55 11 3289 7165 - São Paulo - SP - Brazil
E-mail: sbre@terra.com.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] *Corresponding author. E-mail: luis.andrade@unifesp.br (L.E.C. Andrade).

Autoimmune rheumatic disease n = 32 (10.6%)
	Antiphospholipid syndrome	n = 16 (5.3%)
	Sjögren syndrome	n = 7 (2.3%)
	Systemic sclerosis	n = 4 (1.3%)
	Rheumatoid arthritis	n = 4 (1.3%)
	Polymyositis	n = 2 (0.6%)
	Psoriatic arthritis	n = 1 (0.3%)

Non-rheumatic autoimmune disease n = 20 (6.6%)
	Hypothyroidism	n = 15 (5%)
	Psoriasis	n = 3 (1%)
	Vitiligo	n = 3 (1%)
	Primary biliary cirrhosis	n = 1 (0.3%)
	IgA nephropathy	n = 1 (0.3%)

Primary immunodeficiency disease (Classical and non-Classical) n = 84 (28%)
	SIgMD ^a a Non-classic PID.	n = 24 (8%)
	SIgAD	n = 3 (1%)
	Def IgG	n = 1 (0.3%)
	Def IgG1	n = 5 (1.6%)
	Def IgG2	n = 40 (13.3%)
	Def IgG3	n = 24 (8%)
	Def IgG4	n = 11 (3.6%)
	CGD gene carrier	n = 1 (0.3%)

Infections n = 28 (9.33%)
	Airway infection	n = 9 (3%)
	Urinary tract infection	n = 15 (5%)
	Furunculosis	n = 3 (1%)

	Herpes simplex	n = 2 (0.6%)
	Herpes zoster	n = 2 (0.6%)
	Tuberculosis	n = 1 (0.3%)
	Hanseniasis	n = 1 (0.3%)