Table 2.
Novel autoantibodies in Sjögren’s syndrome.
| Author | Number of patients | Autoantibodies | Technique | Prevalence | Sensitivity and specificity | Clinical features |
|---|---|---|---|---|---|---|
| Hu Q at al. (63) | Meta-analysis | Anti-alpha fodrin | Immunoblot and ELISA | 38-42% | Sensitivity 39.3%Specificity 83% | Moderate accuracy for the diagnosis of SjS.Clinical manifestations were not evaluated. |
| Willeke P et al. (64) | 62 | ELISA | 31-35% | Sensitivity 31-35%Specificity unknown | Shorter disease duration. Increased prevalence of recurrent parotid swelling with IgG isotype. | |
| Mona M et al. (65) | 156 | Anti-muscarinic type 3 receptor (M3R) | On-Cell-Western assay | N/A | Sensitivity 75-98%Specificity 85% | Correlated with ocular dryness and glandular hypofunction and the haematological/biological domains of ESSDAI. Useful in SjS diagnosis, especially where clinical assessments are limited. |
| Deng C et al. (66) | 956 | ELISA | N/A | Sensitivity 4-98%Specificity 58-100% | Potential diagnostic biomarker for SjS.Clinical features were not evaluated. | |
| Shen L et al. (67) | 123 | Anti-salivary gland protein 1 (SP1) | ELISA | 19% isolated34% associated to other autoantibodies. | N/A | Associated with anti-Ro/SSA and anti-La/SSB. No distinct clinical manifestations were identified in patients expressing anti-SP1. |
| Xuan J et al. (68) | 134 | Western-blot | 40% | N/A | Higher levels during earlier stages of the disease. | |
| Karakus S et al. (69) | 136 | N/A | 27 % | N/A | Dry eye. Correlated with having a Schirmer test ≤ 5 mm. | |
| Karakus S et al. (69) | 136 | Anti-carbonic anhydrase 6 (CA6) and anti-parotid secretory protein (PSP) | N/A | 27% (CA6)54% (PSP) | N/A | Anti-CA6 was associated with severe ocular surface staining (corneal and conjunctival). Anti-CA6 may indicate early stages of SjS.Anti-PSP was the only autoantibody that correlated with primary SjS. |
| Pertovaara M et al. (70) | 74 | Carbonic anhydrase auto-antibodies (CA) | ELISA | N/A | N/A | CA-II, CA-VI and CA XIII (associated with renal manifestations).CA-VII and CA-XIII (correlated to β2 microglobulin)CA-I (oral dryness and associated with interstitial lung disease in other connective tissue diseases). |
| Alunno A et al. (71) | 30 | Anti-Interferon-Inducible Protein-16 | ELISA | 33% | N/A | Pathogenesis of glandular inflammation. |
| Baer AN et al. (72) | 133 | ELISA | 29% | N/A | Severe disease: greater prevalence of abnormal Schirmer’s test, ANA >1:320 and germinal center-like structures in the labial salivary gland lymphocytic infiltrates. Focus scores were significantly higher. | |
| Alunno A et al. (73) | 67 | ELISA | 34% | N/A | Pathogenesis of glandular inflammation. | |
| Uomori K et al. (74) | 72 | Anti-NA-14 | ELISA | 11.1% | N/A | Elevation of IgA levels. Low prevalence of ANA positive patients. Disease duration tended to be shorter (although the difference did not reach statistical significance). |
| Liu Y et al. (75) | 100 | Anti-MDM2 | ELISA | 21% | N/A | Longer disease duration and more lymphocytes focal gathering in labial gland. Higher prevalence of anemia, thrombocytopenia and anti-Ro/SSA. |
| Duda S et al. (76) | 72 | Anti-stathmin-4 | ELISA | 33% (pSS with PNP)7.8% (pSS without PNP)15% in sSS | N/A | Polyneuropathy. |
| Zhang YM et al. (77) | 79 | Anti-PUF60 | ELISA and immunoblotting | 10.1% | N/A | Overlap syndrome with myositis. |
| Fiorentino DF et al. (78) | 84 | ELISA | 30% | Specificity 29% | May be more associated with Asian and African-American ethnicity, hypergammaglobulinemia, anti-Ro/SSA, anti-La/SSB and rheumatoid factor. | |
| Lauvsnes MB et al. (79) | 66 | Anti-NR2 | ELISA in serum and electrochemiluminescence in CSF | 20% | N/A | Cognitive disturbances and mood disorders. |
| Lauvsnes MB et al. (80) | 50 | Electrochemiluminescence in CSF | 12% | N/A | Loss of hippocampal gray matter. | |
| Tjensvoll AB et al. (81) | 71 | Electrochemiluminescence in CSF | N/A | N/A | Cognitive impairment. | |
| Wolska N et al. (82) | 235 | Anti-TRIM38 | TNT Quick coupled transcription/translation system and immunoprecipitation assay | 10.21% | N/A | Higher severity of disease: severe sialadenitis, higher van Bijsterved scores and lower Schirmer’s test scores. |
| Birbaum J et al. (83) | 209 | Anti-calponin-3 | ELISA | 11% | N/A | Neuropathy. |
| Alunno A et al. (84) | 104 | Anti-saccharomyces cerevisiae (ASCA) | Immunodot test | 4.8% | Very low sensitivity, 100% specificity | Patients displayed a triple combination of circulating anti-Ro60/SSA, anti-Ro/52/SSA and anti-La/SSB antibodies associated with low complement and cutaneous involvement. |
| Birnbaum J et al. (85) | 109 | Anti-aquaporin (AQ) | Fluorescence-activated cell sorting (FACS) assay | 10% | N/A | Neuromyelitis optica spectrum disorder. |
| Alam J et al. (86) | 112 | Indirect immunofluorescence assay | 76.8% | Sensitivity 73%Specificity 68% | Low resting salivary flow. | |
| Tzartos JS et al. (87) | 34 | ELISA verified by radioimmunoassay, western blot and AQP-transfected cells. | 38.2% | N/A | Severe xeropthalmia, suggesting a potential pathogenic role. | |
| Mukaino et al. (88) | 39 | Anti-ganglionic acetylcholine receptor (gAChR) | LIPS assay | 23.1% | N/A | Autonomic symptoms. |
| Hu YH et al. (89) | 70 | Anti-P-selectin | ELISA | 40.6% (SjS patients with thrombocytopenia) and 7.8% (SjS patients without thrombocytopenia). | N/A | May lead to platelet destruction and endothelial injury. Possible role in the pathogenesis of thrombocytopenia. |
| Zhang Y et al. (90) | 50 | Anti-moesin | ELISA | 42% | N/A | N/A |
| Bergum B et al. (91) | 78 | Anti-carbamylated | ELISA | 27% | N/A | Increased focal lymphocytic infiltration, formation of ectopic GC-like structures in minor salivary glands and diminished salivary gland function. |
| Cui L et al. (92) | 70 | Anti-cofilin-1 | ELISA in saliva samples | N/A | Sensitivity 80%Specificity 90% | May predict progression to MALT lymphoma |
| Cui L. et al. (92) | 70 | Anti-alpha-enolase | ELISA in saliva samples | N/A | Sensitivity 90%Specificity 84% | May predict progression to MALT lymphoma |
| Cui L. et al. (92) | 70 | Anti-Rho GDP-dissociation inhibitor 2 (RGI2) | ELISA in saliva samples | N/A | Sensitivity 90%Specificity 80% | May predict progression to MALT lymphoma |
ELISA, enzyme-linked immunosorbent assay; SjS, Sjögren’s Syndrome; ESSDAI, EULAR Sjögren’s syndrome disease activity index; ANA, antinuclear antibodies; anti-NA-14, nuclear autoantigen of 14 KDa; anti-MDM2, human homologue of mouse double minute 2; pSS, primary Sjögren ‘s Syndrome; sSS, secondary Sjögren’s Syndrome; anti-PUF60, poly(U)-binding-splicing factor 60 KDa; anti-NR2, N-methyl-D-aspartic acid receptor 2; CSF, cerebrospinal fluid; anti-TRIM38, tripartite motif-containing protein 38; LIPS assay, luciferase immunoprecipitation system assay; MALT, mucosa-associated lymphoid tissue; N/A, not available.