Table 1 Genomics studies in rheumatic diseases

RA

Synovium

13 RA

16,164

Intra- and interindividual patients

Gene expression differences between patients are greater than between biopsies obtained from the same joint

RA

Synovium

5 RA and 10 OA

5,760

RA versus OA

Genes differentially expressed between RA and OA

RA

Synovium

21 RA and 9 OA

11,500 and 18,000

Within RA and versus OA

Evidence for the existence of multiple pathways of tissue destruction and repair

RA

Synovium

12 early and 4 late

23,040

Early versus longstanding RA

Early RA fell into two groups based on differences in genes critical for proliferative inflammation

RA

Synovium

10 RA

30,000 cDNA spots

Before versus after about 9 weeks of infliximab

Genes specifically changed in patients who have a good response to infliximab treatment.

RA

Synovium

18 RA

18,000

Responders versus nonresponders to infliximab treatment

Patients with high expression levels of genes involved in tissue inflammation before treatment are more likely to benefit from Infliximab therapy.

RA

Synovium

12 RA

11,500 and 18,000

Within RA

Identification of IL-7 signalling pathway in tissues characterized by lymphoid neogenesis

RA

FLS

19 RA

18,000

Within RA

Heterogeneity between synovial tissues is reflected in FLSs

RA

FLS

2 RA

12,600

Resting versus TNF-α or IL-1β4-hour stimulated cells

Identification of TNF-α and IL-1β regulated genes in RA FLSs

RA

FLS

5 RA and 5 HC

588

RA versus HC

Over-expression of genes responsible for tumor-like growth in RA FLSs

RA

Whole blood

35 RA and 15 HC

18,000

Within RA and versus HC

Assignment of a type I IFN signature in a subpopulation of Patients

RA

PBMC

19

4,300

Early versus longstanding RA

Gene signature in early disease overlaps with normal response to virus

RA

PBMC

29 RA and 21 HC

12,626

RA versus HC

Monocyte associated gene signature increased in RA

RA

PBMC

33

10,000

Before versus 3 months after infliximab

Gene expression profile correlating with treatment response

RA

PBMC

8 RF⁺, 6 RF^- and 7 HC

10,000

RF⁺ versus RF^- and versus HC

No genes differentially expressed between RF⁺ and RF^- RA patients. Increased expression of immunoinflammatory response genes, especially those related to phagocytic functions, in RA

RA

PBMC

19

18,500

Before versus 72 hours after etanercept

Gene pairs and triplets predictive for response to treatment at an early stage of treatment

RA

B-cells

8 RA versus 8 HC

21,329

RA versus HC

Dysregulated B-cell biology in RA is multifaceted

SSc

Skin biopsies

24 SSc and 6 HC

33,000

Within SSc and versus HC

A 177-gene signature associated with severity of skin disease in diffuse SSc

SSc

Dermal fibroblasts

15 SSc twins and 5 HC

16,659

Lesional versus nonlesional and versus twin pair and versus HC

At the molecular level, concordance for the SSc fibroblast phenotype is high in MZ twins and greatly exceeds that in DZ twins

SSc

Dermal non-lesional fibroblasts

21 SSc and 18 HC

16,659

Lesional versus nonlesional and versus HC

Fibroblasts from nonlesional sites in SSc have detectable abnormalities in a variety of cellular processes, including ECM formation, fibrillogenesis, angiogenesis and complement activation

SSc

PBMC

18 SSc and 18 HC

16,659

SSc versus HC

Differentially regulated expression of genes involved in IFN and vasculopathy

SSc

PBMC

9 early diffuse SSc and 4 HC

38,500

SSc versus HC

Type I IFN induced Siglec-1 is increased on circulating SSc CD14⁺ monocytes

SS

Minor salivary glands

10 SS and 10 HC

6,803

SS versus HC

Increased expression of genes involved in chronic inflammation and type I IFN

SS

Minor salivary glands

7 SS and 7 HC

7,261

SS versus HC

Activation of IFN pathways in SS

SS

Whole saliva

10 SS and 8 HC

38,500

SS versus HC

Activation of IFN pathway in SS

SLE

Synovium

6 SLE, 7 RA and 6 OA

38,500

SLE versus RA versus OA

The different diseases were characterized by distinct molecular signatures. Upregulation of IFN-induced genes and downregulation of genes involved in ECM homeostasis in SLE

SLE

Glomeruli

12 SLE and 4 HC

3,602 and 4,030

SLE versus HC and within SLE

Characterization of heterogeneity in the molecular pathogenesis of lupus nephritis

Paediatric SLE

PBMC

30 SLE, 12 JCA and 9 controls

12,626

SLE versus JCA versus controls

IFN signature in the majority of SLE patients and upregulation of granulocyte specific transcripts

SLE

PBMC

48 SLE and 42 HC

10,260

Within SLE and versus HC

About half of the patients studied exhibited dysregulated expression of genes in the IFN pathway associated with more severe disease

SLE

Whole blood

269 patients

256

Within SLE

Categorization of SLE patients into two groups based on a high or low IFN signature. Disease activity correlates with the high IFN signature

Paediatric SoJIA

PBMC

44 SoJIA, 94 infected patients, 38 SLE, 6 PAPA and 39 healthy controls

17,454

SoJIA versus controls

A SoJIA-specific gene signature containing 88 genes. Blood transcriptional patterns in the systemic phase of SoJIA are more similar to those of patients with infections than to those of SoJIA patients in a later arthritic stage of disease

Paediatric SoJIA

PBMC

8 untreated and 5 infliximab treated SoJIA

17,454

Treated versus untreated Patients

Increased expression of type I IFN regulated genes in the anti-TNF treated SoJIA patients, suggesting cross-regulation between TNF and type I IFN

Autoimmune diseases

PBMC

20 RA, 24 SLE, 5 type I diabetes, 4 MS and 9 HC

4,329

Between autoimmune disease

Overlapping gene expression profiles in RA, SLE, type I diabetes and MS, which is distinct from a normal immune response profile

RA, SLE

Whole blood

6 HC, 4 RA, 4 SLE and 5 family members

4,000

RA versus SLE versus HC versus family

Shared autoimmune gene expression signature in patients and unaffected first-degree relatives