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Table 1

From: Contributions of mass spectrometry-based proteomics to defining cellular mechanisms and diagnostic markers for systemic lupus erythematosus

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
  1. 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).