Table 2.
Association between DNA methylation-based IFN score status and clinical parameters and disease manifestations in patients with primary Sjögren’s syndrome (pSS) summarized for discovery and replication cohorts together.
| Phenotype‡ | Discovery and replication cohort together, n=148 | ||
|---|---|---|---|
| High IFN score | Low IFN score | P-value | |
| Mean (±s.d.) | |||
| Age at DNA sampling (years) | 53.7 (±13.2) | 60.1 (±13.6) | 2.5x10-3 |
| Age at diagnosis (years) | 48.2 (±13.7) | 55.0 (±12.8) | 3.0x10-3 |
| Age at symptom onset (years) | 41.6 (±15.1) | 48.5 (±14.6) | 0.017 |
| Disease duration (years) | 5.8 (±6.1) | 5.1 (±5.3) | 0.61 |
| Focus score | 3.5 (±3.2) | 2.8 (±2.9) | 0.26 |
| N/available (%) | |||
| Female sex | 77/87 (89%) | 53/61 (87%) | 1 |
| ANA | 78/87 (90%) | 39/61 (64%) | 0.24 |
| SSA | 82/87 (94%) | 28/61 (46%) | 0.012 |
| Ro52 | 39/47 (83%) | 12/35 (34%) | 0.039 |
| Ro60 | 43/47 (91%) | 9/35 (26%) | 4.2x10-3 |
| SSB | 50/87 (57%) | 12/61 (20%) | 4.0x10-3 |
| Positive for any of the included autoantibodies | 86/87 (99%) | 45/61 (74%) | 0.29 |
| Leucopenia (< 4.0x109/L) | 39/86 (45%) | 17/60 (28%) | 0.21 |
| P-IgG > 15 g/L | 52/74 (70%) | 13/53 (25%) | 4.5x10-3 |
| C3 below normal limit | 7/76 (9%) | 6/43 (14%) | 0.55 |
| C4 below normal limit | 12/42 (29%) | 0/21 (0%) | 0.016 |
| GC formation in minor salivary glands | 10/38 (26%) | 6/33 (18%) | 0.59 |
| Raynaud’s phenomenon | 28/86 (33%) | 25/61 (41%) | 0.58 |
| Arthritis | 13/86 (15%) | 8/61 (13%) | 0.95 |
| Purpura | 8/86 (9%) | 2/61 (3%) | 0.32 |
| Lymphadenopathy | 16/86 (19%) | 12/61 (20%) | 1 |
| Hypothyroidism | 21/86 (24%) | 14/61 (23%) | 1 |
| Lymphoma, all | 9/87 (10%) | 6/61 (10%) | 1 |
‡Clinical manifestations presented ever, with autoantibody status retrieved from time point nearest to DNA sampling.
IFN score status defined as high IFN score (>meanctrl +2s.d.ctrl, >4.4) or low IFN score (≤4.4).
Patients with pSS were stratified on IFN score status (high versus low) and continuous variables between groups were tested using Mann-Whitney U. Categorical variables were assessed using X2-test, or for sparse data using Fisher’s exact test.
ANA, antinuclear antibodies; C3, complement component 3; C4, complement component 4; DNAm, DNA methylation; GC, germinal center; IFN, interferon; n.a., not available; s.d., standard deviation; SSA, anti-Sjögren’s syndrome antigen A antibodies (Ro52 and/or Ro60); SSB, anti-Sjögren’s syndrome antigen B antibodies (La).
Significant p-values in bold.