Systemic Lupus Erythematosus, An Issue of Rheumatic Disease Clinics (eBook)

Ellen M. Ginzler (Autor)

eBook Download: PDF | EPUB

2014 | 1. Auflage
185 Seiten
Elsevier Health Sciences (Verlag)
978-0-323-32388-8 (ISBN)

Infos

In only the last four years, there have been dramatic changes in the understanding of the immunology, genetic/epigenetic associations, and identification of new targets for therapy in Systemic Lupus Erythematosus. The editors have enlisted a superb group of authors to present articles detailing cutting-edge advances in these areas.

Textauszug

Clinical Perspectives on Lupus Genetics

Advances and Opportunities

Judith A. James, MD, PhDab∗[e-mail],     aOklahoma Clinical & Translational Science Institute, University of Oklahoma Health Sciences Center, 920 Stanton L Young Boulevard, Oklahoma City, OK 73104, USA; bDepartments of Medicine, Pathology, Microbiology & Immunology, University of Oklahoma Health Sciences Center, 920 Stanton L Young Boulevard, Oklahoma City, OK 73104, USA

∗Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City, OK 73104.

In recent years, genome-wide association studies have led to an expansion in the identification of regions containing confirmed genetic risk variants within complex human diseases, such as systemic lupus erythematosus (SLE). Many of the strongest SLE genetic associations can be divided into groups based on their potential roles in different processes implicated in lupus pathogenesis, including ubiquitination, DNA degradation, innate immunity, cellular immunity, lymphocyte development, and antigen presentation. Recent advances have also shown several genetic associations with SLE subphenotypes and subcriteria. Many areas for further exploration remain to move lupus genetic studies toward clinically informative end points.

Keywords

SLE

Lupus

Genetics

Clinical subphenotypes

GWAS

Nephritis

Autoantibodies

Key points

• Polymorphisms in genes important for ubiquitination, DNA degradation, innate immunity, cellular immunity, antigen presentation, and lymphocyte development are associated and confirmed in systemic lupus erythematosus (SLE).

• Select genetic associations are enriched in patients with SLE with certain autoantibodies, antiphospholipid syndrome, pericarditis, thrombosis, arthritis, or lupus nephritis.

• New lupus genetic studies are warranted, especially with large cohorts enriched for understudied races, and in patients with severe disease or poor prognosis.

• New lupus genetic studies are also warranted in large cohorts of patients with SLE with phenotype information about common lupus comorbidities and response to therapeutics.

Introduction

Systemic lupus erythematosus (SLE; lupus) is a complex clinical syndrome with a wide range of clinical symptoms and significant immune dysregulation including production of high concentrations of autoantibodies. Lupus cases have been found to cluster in families with 66% heritability and a lambda S between 8 and 29. Monozygotic twin studies have shown 24% to 69% twin concordance rates, compared with the dizygotic twin or sibling rates of 2% to 5%.1–3 Since the first genome-wide association studies (GWAS) conducted in SLE were published in 2008,4–6 the number of associated and confirmed genetic associations has increased greatly, as shown and referenced in Table 1, which summarizes these findings to December 2013.

Table 1

Loci associated with SLE through GWAS, meta-analysis studies, candidate gene studies, or replication studies from 1992 to December 2013

IKBKE

NFκB signaling

1q32.1

rs1539241/rs12142086

EU

94

TNIP1

Ubiquitination in NFκB signaling

5q32

rs10036748

EU, AA, AS

4,15,23,77,95,96

TNFAIP3

Ubiquitination in NFκB signaling

6q23

rs2230926

EU, AA, AS

4,14,23,77,97–99

SLC15A4

Ubiquitination in NFκB signaling

12q24.32

rs1385374

AS

15,23

UBASH3A

Ubiquitination

21q22.3

rs9976767

EU

100

UBE2L3, HIC2

Ubiquitination in NFκB signaling

22q11.21

rs463426

EU, AS

5,23,101,102

IRAK1/MECP2

Ubiquitination in NFκB signaling

Xq37

rs1734787

EU, HA, AS

4,77,103–105

Complement genes

Apoptosis/clearance of debris; neutrophil/monocyte immunity

1q36

Multiple

EU

106–110

IL-2/IL-21

Apoptosis/clearance of debris; neutrophil/monocyte immunity

4q26

rs907715

EU, AA, AS

111,112

ATG5

Apoptosis/clearance of debris

6q21

rs548234

EU, AS

4,5,23,77

ITGAM

Apoptosis/clearance of debris

16p11.2

rs9888739

EU, HA, AS

4–6,77,103,113–115

DNase 1

Apoptosis/clearance of debris

16p13.3

rs8176927

AS, A

116,117

ACP5/TRAP

Apoptosis/clearance of debris

19p13.2

rs79525531

EU, AS, H

118

Mir146a

mRNA stability/translation

6q5

rs57095329

EU, AA, AS

119,120

ZBP2

mRNA stability/translation

17q12

rs1453560

EU, AA

22

IFIH1

TLR/interferon pathways; T-cell immunity

2q24

rs1990760

EU

22

STAT4

TLR/interferon pathways; T-cell immunity

2q23.2

rs7582694

EU, HA, AA, AS

4,5,31,97,103,113,121–123

RASGRP3

TLR/interferon pathways

2p24.1

rs13385731

AS

23

PRDM1

TLR/interferon pathways; B-cell immunity; T-cell immunity

6p21

rs6568431

EU

77

IRF5/TNPO3

TLR/interferon pathways

7q32

rs12537284

EU, HA, AA, AS

4,5,77,101,124–126

PHRF1/IRF7/KIAA1542

TLR/interferon pathways

11p15.5

rs4963128

EU, AA

4,5,23,77

IRF8

TLR/interferon pathways; neutrophil/monocyte immunity

16q24.1

rs116440334

EU

22,127

TLR7

TLR/interferon pathways

Xp22.3

rs3853839

EU, AS

128,129

UHRF1BP1

Cellular growth

6p21

rs11755393

EU

77

TNXB

Cellular adhesion

6p21.32–33

rs310342

AS

130

PXK

Synaptic transmission

3p14.3

rs6445975

EU

4,5,102,113

HIP1

Endocytosis and protein trafficking

7q11

rs6964720

AS

97

NCF2

B-cell immunity

1q25

rs17849502

EU, AS

4,77,111,131

IL-10

B-cell immunity; lymphocyte activation; neutrophil/monocyte immunity

1q31-q32

rs3024505

EU, AA, AS

4,77,101,103,132

BANK1

B-cell immunity

4q24

rs10513487

EU, HA, AA, AS

4,103,133,134

BLK

B-cell immunity

8p3

rs7812879

EU, HA, AA, AS

5,6,23,97,135,136

LYN

B-cell immunity

8q13

rs7829816

EU, AA, AS

5,137

ELF1

B-cell immunity; T-cell immunity

13q13

rs7329174

AS

138

PRKCB

B-cell...

Produkt-Details

• Erscheint lt. Verlag: 28.8.2014
• Sprache: englisch
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Rheumatologie
• ISBN-10: 0-323-32388-X / 032332388X
• ISBN-13: 978-0-323-32388-8 / 9780323323888