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Genetic Causes of Inflammatory Bone Disease

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Textbook of Autoinflammation

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Abstract

This chapter focuses on monogenic autoinflammatory disorders that affect bone. The presence of sterile bone inflammation may be accompanied by inflammation of the skin and intestinal tract. The pathophysiology varies by syndrome and includes dysregulation of the IL-1 pathway or aberrant intracellular signaling defects leading to activation of innate immune cells including osteoclasts. These are rare disorders with variable outcomes. IL-1 inhibitors have been used successfully to decrease inflammation in Majeed syndrome, deficiency of the interleukin receptor antagonist and for non-osseous manifestations of neonatal onset multisystem inflammatory disease. For other disorders such as cherubism, treatment remains challenging. Recognition of additional monogenic autoinflammatory is likely as this is a very new field of investigation.

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Abbreviations

ADP:

Adenosine diphosphate

ASC:

Apoptosis-associated speck-like protein containing a carboxy-terminal CARD

c-ABL:

Abelson murine leukemia viral oncogene homolog 1

CDA:

Congenital dyserythropoietic anemia (CDA)

CNO:

Chronic non-bacterial osteomyelitis

CRMO:

Chronic recurrent multifocal osteomyelitis

CRP:

C-reactive protein

Csk:

C-terminal Src kinase

DIRA:

Deficiency of the interleukin-1 receptor antagonist

ERK:

Extracellular signal-regulated kinase

ESR:

Erythrocyte sedimentation rate

FBLIM1:

Filamin binding LIM protein 1 gene

FBLP1:

Filamin binding LIM protein 1

HPGD:

15-hydroxyprostaglandin dehydrogenase

IL:

Interleukin

IL-1AcP:

IL-1 receptor accessory protein

IL-1RI:

IL-1 receptor I

IL1RN:

Interleukin-1 receptor antagonist gene symbol

IRAK4:

Interleukin 1 receptor associated kinase 4

LPIN2:

Lipin2 gene symbol

MAPK:

MAP kinase

M-CSF:

Macrophage colony-stimulating factor

MRI:

Magnetic resonance imaging

MyD88:

Myeloid differentiation primary response 88

NFAT:

Nuclear factor of activated T-cells

NLRP3:

NLR family pyrin domain containing 3

NOMID:

Neonatal onset multisystem inflammatory disease

NR4A2:

Nuclear receptor subfamily 4 group A member 2

NSAID:

Non-steroidal anti-inflammatory drugs

P2X7R:

Purinergic receptor P2X 7

PAP:

Phosphatidate phosphatase

PHO:

Primary hypertrophic osteoarthropathy

Pstpip2:

Proline-serine-threonine phosphatase interacting protein 2

PTP PEST:

 Protein-tyrosine phosphatase with proline (P), glutamic acid (E), serine (S), and threonine (T) motif

RANKL:

Receptor activator of nuclear factor kappa-Β ligand

SH3BP2:

SH3 binding protein 2

SHIP1:

Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1

STAT:

Signal transducer and activator of transcription

STIR:

Short tau inversion recovery

Syk:

Spleen tyrosine kinase

TNF:

Tumor necrosis factor

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Authors and Affiliations

  1. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    James Verbsky

  2. Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Polly J. Ferguson

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  1. James Verbsky
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  2. Polly J. Ferguson
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Correspondence to Polly J. Ferguson .

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Editors and Affiliations

  1. Pediatric Rheumatology Unit, Shaare Zedek Medical Center and Hebrew University, Jerusalem, Israel

    Philip J. Hashkes

  2. Department Paediatrics, Division of Rheumatology, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada

    Ronald M. Laxer

  3. Department of Internal Medicine, Radboudumc Expertisecenter for Immunodeficiency and Autoinflammation, Radboud University Medical Center, Nijmegen, The Netherlands

    Anna Simon

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Verbsky, J., Ferguson, P.J. (2019). Genetic Causes of Inflammatory Bone Disease. In: Hashkes, P., Laxer, R., Simon, A. (eds) Textbook of Autoinflammation. Springer, Cham. https://doi.org/10.1007/978-3-319-98605-0_25

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