Table 2.
SSc-associated autoantibodies observed in this study
| Alias | Associated proteins | Disease subset | Clinical associations | Prevalence in this dataset (avg/freq) | Reference | |||
|---|---|---|---|---|---|---|---|---|
| Control (n = 4) | RNAP3 (n = 4) | TOP1 (n = 4) | CENP (n = 5) | |||||
| Major autoantibodies | ||||||||
| RNA Pol III | POLR3A | dSSc | Renal crisis, cancer | - | +++ (28/4) | - | - | Graf, et al. 2012 [1]; Mehra, et al. 2013 [3] |
| Scl70 | TOP1 | dSSc | Poor prognosis, internal organ involvement, and proteinuria | + (3/2) | + (4/4) | +++ (19/4) | - | Mehra, et al. 2013 [3] |
| Centromere | CENPB, CENPH | lSSc/CREST | PAH, ILD | - | - | - | + (1/2) | Mehra, et al. 2013 [3] |
| Other SSc autoantibodies present in our dataset | ||||||||
| Endothelial Cell | TUBB, VCL, LMNA, RPLP0 | SSc | PAH | + (1/1) | ++ (6/4) | + (4/2) | + (0/1) | Dib, et al. 2012 [34], Naniwa, et al. 2007 [35] |
| Fibroblast | ENO1, G6PD, HSPA1A, HSPA1B, VIM | SSc | PAH | + (3/4) | +++ (12/4) | ++ (5/3) | ++ (8/5) | Terrier, et al. 2008 [36], Terrier, et al. 2009 [37] |
| Histone | H1FX, HIST1H1B, HIST1H4A | SSc | PF, internal organ involvement, decreased survival | + (1/1) | + (3/3) | + (1/1) | - | Mehra, et al. 2013 [3] |
| B23 | NPM1 | dSSc, CENP- lSSc | PAH | + (4/4) | ++ (7/4) | ++ (5/4) | ++ (6/5) | Mehra, et al. 2013 [3] |
| Ku | XRCC5, XRCC6 | lSSc | Myositis | + (3/3) | +++ (12/4) | ++ (8/4) | + (2/3) | Graf, et al. 2012 [1]; Mehra, et al. 2013 [3] |
| Su | AGO2 | SSc, PM/Scl | Unknown | - | + (1/2) | + (3/1) | - | Satoh, et al. 2013 [38] |
| Mitochondrial (M2) | DLD, PDHB | lSSc | Strong association with primary biliary cirrhosis | + (1/1) | + (2/3) | + (1/1) | - | Mehra, et al. 2013 [13] |
| Pm/Scl | EXOSC1-10 | SSc | PF, digital ulcers; decreased risk of PAH and GI symptoms | + (2/2) | ++ (5/3) | + (2/2) | - | Mehra, et al. 2013 [13] |
| hnRNPs | HNRNPA1-3, HNRNPL | SSc | Common in SARDs | + (0/1) | ++ (7/4) | + (3/4) | + (2/4) | Siapka, et al. 2007 [39] |
| U1 | SNRNPA, SPRNP70 | SSc | Co-occurrence with SS-A/SS-B, PAH, overlap syndrome | - | + (2/4) | + (1/2) | + (0/1) | Graf, et al. 2012 [1]; Mehra, et al. 2013 [3] |
| U5 | SNRNP200 | SSc, PM/Scl | Unknown | ++ (6/3) | ++ (9/4) | ++ (8/3) | + (1/2) | Kubo, et al. 2002 [40] |
| RO52/TRIM21 | TRIM21 | SSc | ILD, other autoimmune diseases | ++ (6/3) | +++ (12/4) | ++ (6/4) | ++ (8/4) | Mehra, et al. 2013 [3] |
| RuvB | RUVBL1, RUVBL2 | dSSc | Common in SARDs, older age at onset, male sex | + (1/1) | ++ (7/4) | + (3/4) | + (2/4) | Kaji, et al. 2014 [18] |
| Annexin V | ANXA5 | dSSc, CENP- lSSc | Digital ischemia | + (2/2) | ++ (7/4) | + (4/3) | + (3/4) | Mehra, et al. 2013 [3] |
| SS-B/LA | SS-A, SS-B | SSc | ILD, other autoimmune diseases | - | + (3/4) | + (2/2) | + (0/1) | Mehra, et al. 2013 [3] |
| Peroxiredoxin | PRDX1 | SSc | Disease duration, PF, cardiac involvement, TOP1+ patients | + (2/4) | ++ (8/4) | + (3/3) | + (4/4) | Mehra, et al. 2013 [3] |
| hUBF/NOP90 | UBTF | lSSc | Mild organ involvement, favorable prognosis | - | + (1/2) | - | - | Mehra, et al. 2013 [3] |
| Th/To | POP1 | lSSc | PF, renal crisis, poor prognosis, myositis, PAH | + (1/2) | + (1/1) | + (3/3) | - | Graf, et al. 2012 [1]; Mehra, et al. 2013 [3] |
| PL-12 | AARS | SSc, PM/DM | ILD without myositis | - | - | + (1/1) | + (1/1) | Hamaguchi, et al. 2013 [19] |
| OJ | IARS | SSc, PM/DM | ILD without myositis | + (1/1) | - | + (3/3) | - | Hamaguchi, et al. 2013 [19] |
| EJ | GARS | SSc, PM/DM | ILD, myositis | - | + (3/4) | + (2/2) | + (0/1) | Hamaguchi, et al. 2013 [19] |
| Jo-1 | HARS | SSc, PM/DM | ILD, myositis | - | + (1/4) | - | - | Hamaguchi, et al. 2013 [19] |
| PL-7 | TARS | SSc, PM/DM | ILD, myositis | + (2/2) | ++ (8/4) | ++ (6/4) | + (2/4) | Hamaguchi, et al. 2013 [19] |
| Ha | YARS | SSc, PM/DM | Interstitial pneumonia | - | + (0/1) | - | - | Hashish, et al 2005 [41] |
| Zo | FARSA, FARSB | SSc, PM/Scl | Anti-synthetase syndrome | - | + (2/4) | - | - | Betteridge, et al. 2007 [42] |
| SSc autoantibodies not detected in our dataset | ||||||||
| Fibrillarin | U3RNP | dSSc | More frequent in blacks; severe disease, poor prognosis | - | - | - | - | Mehra, et al. 2013 [3] |
| U11/U12 RNP | SNRNP35 | SSc | Lung fibrosis, gastrointestinal involvement | - | - | - | - | Mimori, 1999 [43] |
| PDGFR | PDGFR | SSc | Unknown | - | - | - | - | Svegliati Baroni, et al. 2006 [44] |
| MMP | MMP family | dSSc | Skin, lung, and vascular fibrosis | - | - | - | - | Mehra, et al. 2013 [3] |
| tPA | PLAT | lSSc | PAH | - | - | - | - | Mehra, et al. 2013 [3] |
| IFI16 | IFI16 | lSSc | Common in SARDs | - | - | - | - | Mehra, et al. 2013 [3] |
| Fibrillin 1 | FBN1 | dSSc | Choctaw and Japanese patients; absent in Caucasians | - | - | - | - | Mehra, et al. 2013 [3] |
| Vascular Receptors | AGTR2, EDN1 | SSc | TOP1+ patients, renal crisis | - | - | - | - | Mehra, et al. 2013 [3] |
| ATF2 | ATF2 | SSc | Longer disease duration, decreased lung function | - | - | - | - | Mehra, et al. 2013 [3] |
Data are presented as the average of all peptide hits across each autoantibody group, followed by the frequency of peptide detection within the group. For autoantibodies known to target more than one protein or subunit, data for a single representative protein are shown, with the specific protein highlighted in bold. Associated proteins indicate specific protein targets identified in this study; among autoantibodies not identified here, the most common targets are listed. Symbols: -, +, ++, and +++ indicate an average of 0, 1–4, 5–9, and ≥10 peptide hits per group, respectively
SSc systemic sclerosis, lSSc limited cutaneous SSc, dSSc diffuse cutaneous SSc, PAH pulmonary arterial hypertension; ILD interstitial lung disease; CREST CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia); PM/Scl polymyositis/scleroderma, PM/DM polymyositis/dermatomyositis