Skip to main content

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).