Table 1.
| Protein identified | MS platform | Authors' conclusion | Biomarker or mechanistic |
|---|---|---|---|
| Cardiovascular SLE | |||
| Haptoglobin (Hp)α2 [23] | MALDI-TOF-TOF and ESI-MS/MS | Higher plasma Hpα2 seen in SLE versus controls Supporting research has implicated Hpα2 isoforms in cardiac complications [24,25] |
Both |
| Ro52 [19] | MALDI-TOF-TOF | Antibody protected sites found with SLE sera in portion of the Ro52 protein comprising amino acids 200 to 239 | Both |
| Annexin A6 [10] | LC-MS/MS | Autoantibodies identified against annexin A6 Activation of annexin A6 via autoantibody resulting in impaired heart function |
Both |
| Immune cell involvement in SLE | |||
| Immunoglobulin J [27] | MALDI-TOF | Upregulated in SLE 2.46-fold Early differentiation marker for B cells |
Both |
| Calprotectin L1 [27] | MALDI-TOF | Upregulated in SLE 2.02-fold Known marker of disease activity in RA Released from granulocytes and monocytes during their activation Significantly tied to SLEDAI and higher levels of anti-double-stranded DNA antibodies and SLE arthritis May also inhibit immunoglobulin production |
Both |
| Glutathione S-transferase [18,27] | MALDI-TOF and iTRAQ 2D LC-MS/MS | Downregulated in SLE 0.15-fold (P = 0.001) in one study and versus diseased and healthy controls Lower GST results in higher ROS levels and increased oxidative stress Polymorphisms with altered enzyme activity of GST have been shown to lead to SLE |
Both |
| Apolipoprotein A-IV precursor [27] | MALDI-TOF | Upregulated in SLE 2.67-fold (P = 0.010) Similar results seen in RA [70] and Alzheimer's disease [71] |
Biomarker |
| Zinc finger protein subfamily 1A [27] | MALDI-TOF | Upregulated in SLE 2.24-fold (P = 0.041) | Both |
| Zinc finger protein - isoform 2 protein 549 [18] | iTRAQ 2D LC-MS/MS | Upregulated in active SLE versus stable SLE (2.7160), RA (2.3824) and healthy controls (3.1042) | Both |
| Resistin [18] | iTRAQ 2D LC-MS/MS | Upregulated in active SLE versus stable SLE (3.6784) and healthy controls (2.2652) Verifies previous findings | Both |
| S100-P [18] | iTRAQ 2D LC-MS/MS | Upregulated in active SLE versus stable SLE (2.9641), and healthy controls (2.6475) | Both |
| S100-A12 [18] | iTRAQ 2D LC-MS/MS | Upregulated in active SLE versus stable SLE (2.3374), RA (2.0595) | Both |
| Brain acid soluble protein 1 [18] | iTRAQ 2D LC-MS/MS | Upregulated in active SLE versus stable SLE (2.1139), healthy controls (2.6622) | Both |
| Ras-related C3 botulism toxin substrate 2 [18] | iTRAQ 2D LC-MS/MS | Downregulated in stable SLE (0.4663) versus diseased controls | Both |
| Lupus nephritis | |||
| α-1 Acid glycoprotein [34] | 2-DE then MALDI-TOF | Diagnosis and class identification of LN | Biomarker |
| α1 Microglobulin [34] | 2-DE then MALDI-TOF | Diagnosis and class identification of LN | Biomarker |
| Zinc α-2 glycoprotein [34] | 2-DE then MALDI-TOF | Diagnosis and class identification of LN | Biomarker |
| IgG k light chain [34] | 2-DE then MALDI-TOF | Diagnosis and class identification of LN | Biomarker |
| α-1 Antitrypsin [36] | SELDI-TOF then LC-MS/MS | Upregulated in the urine at baseline and 2 months pre-flare until 4 months post-flare | Biomarker |
| Albumin [36] | SELDI-TOF then LC-MS/MS | Upregulated in the urine at baseline versus flare | Biomarker |
| Hepcidin-20 [36,37] | SELDI-TOF then LC-MS/MS | Upregulated in the urine 4 months pre-flare | Biomarker |
| Aldolase A [20] | LC-MS/MS | Autoantibodies more common in LN patients than SLE without LN Antibody specific to a 94 to 183 amino acid epitope may be LN-specific biomarker |
Biomarker |
| Pediatric lupus nephritis | |||
| Transferrin (Tf) [38,39] | SELDI-TOF then MALDI-TOF MS/MS | Upregulated in worsening disease and flares in pediatric patients Plasma Tf related to global SLE activity Urine Tf was related to LN disease activity |
Biomarker |
| Ceruloplasmin (Cp) [38,39] | SELDI-TOF then MALDI-TOF MS/MS | Upregulated in pediatric SLE and LN, but cannot specify between different classes of LN activity | Biomarker |
| α1-Acid-glycoprotein (AGP) [38,39] | SELDI-TOF then MALDI-TOF MS/MS | AGP from plasma is for global pediatric SLE AGP from urine is specific to pediatric LN Useful to anticipate renal flares |
Biomarker |
| Lipocalin [38,39] | SELDI-TOF then MALDI-TOF MS/MS | Type prostaglandin-D synthetase (L-PGDS) - role in chemotherapy induced renal damage (plasma and urine) Novel to LN |
Biomarker |
| Aldolase A [20] | LC-MS/MS | Anti-aldolase A antibodies have been found to be more common in SLE with LN than SLE without LN (43.4% to 11.1%) Possible specificity for other autoimmune conditions via presence of antibodies to the 94 to 183 amino acid epitope |
Biomarker |
| Neurophychiatric SLE | |||
| Intermediate filament α-internexin (INA) [8] | 2-DE then MALDI-TOF | Reactive antibodies found in NPSLE patient sera in 41.7% of patients (7.1% of SLE, 0% healthy controls and 10% of other neurological diseases) Results verified [45] |
Both |
| α-Tubulin [43] | MALDI-TOF then Q-TOF | Autoantibodies were found in 36% of NPSLE (versus 4% of SLE and 0% healthy controls) More frequently seen in severe (50%) than mild (20%) NPSLE Confirmed by LC-MS/MS [9] |
Both |
| α-Tubulin [43] | MALDI-TOF then Q-TOF | Previously identified in other autoimmune conditions such as multiple sclerosis and Guillain-Barre syndrome Confirmed by LC-MS/MS [9] |
Both |
| Crystalline αB [9] | LC-MS/MS | Novel sera and CSF autoantigen for active NPSLE | Both |
| Esterase D [9] | LC-MS/MS | Novel sera and CSF autoantigen for active NPSLE | Both |
| APEX nuclease 1 [9] | LC-MS/MS | Novel sera and CSF autoantigen for active NPSLE More reactive in SLE than other autoimmune conditions |
Both |
| 60 kDa Heat shock protein [45] | LC-MS/MS | Autoantibodies directed against cerebral lysates found in sera of NPSLE patients with WMH Known to cause endothelial cell apoptosis and coronary artery disease Results verified [32] |
Both |
| Anti-Rab guanosine diphosphate dissociation inhibitor α [31] | LC-MS/MS | Found in 80% of NPSLE patient sera with psychosis (versus 5.3% of NPSLE without psychosis and none of the CNS control samples) |
Both |
1D, one-dimensional; 2D, two-dimensional; 2-DE, two-dimensional electrophoresis; AGP, α1-acid-glycoprotein; CNS, central nervous system; CSF, cerebral spinal fluid; ESI, electrospray ionization; GST, glutathione S-transferase; iTRAQ, isobaric tagging for relative and absolute protein quantification; LC, liquid chromatography; LN, lupus nephritis; L-PGDS, lipocalin-type prostaglandin-D synthetase; MALDI-TOF, matrix associated laser desorption/ionization-time of flight; MS/MS, tandem mass spectrometry; NPSLE, neuropsychiatric systemic lupus erythematosus; RA, rheumatoid arthritis; ROS, reactive oxygen species; SELDI, surface enhanced laser desorption/ionization; SLE, systemic lupus erythematosus; SLEDAI, SLE Disease Activity Index; Tf, tranferrin; WMH, white matter hypertrophies (on MRI).