Table 2.
Summary of Studies Investigating Protein Changes in Sarcoidosis
| Study | Tissue Type Studied | Sarcoidosis | Control Subjects | Proteomics Method | Findings |
|---|---|---|---|---|---|
| Magi 2002 (83) | BALF | Active sarcoidosis (n = 6) | IPF (n = 6) | 2DE | Thirty-two protein spots with differential expression, of which 15 were more abundant in sarcoidosis |
| Sabounchi-Schütt 2003 (84) | BALF | Acute onset LS (n = 6) | Healthy (n = 4) | 2DE-MALDI-TOF | Seventeen protein spots different in sarcoidosis; seven proteins not previously reported in BALF were also identified |
| Sabounchi-Schütt 2004 (27) | Serum | Sarcoidosis (n = 6) | Healthy (n = 4) | 2DE and MALDI-TOF | Twenty-two protein spots were different between subjects with sarcoidosis and control subjects, 14 were more abundant and eight were less abundant in sarcoidosis. Nineteen spots had a statistically significant difference. Eleven proteins were identified from thee protein spots |
| Kriegova 2006 (55) | BALF | Stage I (n = 32 [LS = 14; NLS = 18]), stage II (n = 22), and stage III (n = 11) | Healthy (n = 23) | SELDI-TOF MS | Forty differentially expressed protein peaks, of which three were identified to be protococadherein-2 precursor, HSA, and alpha-1 antitrypsin |
| Rottoli 2005 (88) | BALF | Active sarcoidosis (n = 11) | IPF (n = 10) and SSc pulmonary fibrosis (n = 10) | 2DE and cellular profile by flow cytometry. | An increase in plasma protein in BALF from sarcoidosis and SSc and more locally produced lower molecular weight proteins in IPF |
| Rottoli 2005 (87) | BALF | Active sarcoidosis | IPF (n = 10) and SSc pulmonary fibrosis (n = 10) | Carbonylated proteins assessed by ELISA | Increase in carbonylated proteins in the subjects with diffuse lung diseases compared with control subjects. Patients with IPF had more carbonylation protein targets, including plasmatic proteins and transferrin immunoglobulin light chain, and IgA. Albumin and immunoglobulin heavy chain target carbonylated in all cases and control subjects and may act as a buffer and prevent other proteins from oxidant damage |
| Silva 2007 (86) | BALF | Sarcoidosis (n = 4) | Chronic beryllium disease (n = 4) and control subjects (n = 5) | DIGE coupled with MALDI-TOF | Sixteen protein spots and five proteins were different in subjects with sarcoidosis versus control subjects. Seventeen protein spots and eight proteins were different in subjects with CBD and control subjects, and one protein was downregulated in sarcoidosis compared with CBD. One protein was more abundant in sarcoidosis (compared with CBD) and could not be identified |
| Landi 2013 (89) | BALF | Sarcoidosis (n = 9) | IPF (n = 7), PLCH (n = 9), and SSc pulmonary fibrosis, n = 7 | 2DE with MALDI-TOF MS/MS | An average of 1,000 spots were identified in each gel, and 154 spots were differentially expressed in various comparisons corresponding with 77 proteins. The proteins mapped to biological pathways involved in defense, inflammation, and response to stress |
| Silva 2013 (19) | Soluble protein fraction from alveolar macrophages | Sarcoidosis (n = 7) | Healthy (n = 7) | DIGE followed by MALDI-TOF | Sixty-nine protein spots were significantly different, corresponding with 25 unique proteins (17 upregulated and eight downregulated) in sarcoidosis. Clathrin mediated endocytosis and Fcχ receptor mediated phagocytosis |
| Du 2015 (25) | Serum | Sarcoidosis (n = 20) | Tuberculosis (n = 20) and healthy control subjects (n = 20) | Human cytokine antibody array | ICAM-1 and leptin discriminate cases with sarcoidosis from those with tuberculosis. |
| Landi 2015 (85) | BALF | Stage II/III active pulmonary sarcoidosis (n = 9) | Nonsmokers (n = 10) and smokers (n = 8) | 2DE and MALDI-TOF MS or LC MS/MS | Differentially expressed proteins map to PI3K/Akt/mTOR, MAP kinase, pluripotency-associated transcriptional factor, and hypoxia response pathway |
| Häggmark 2015 (26) | BALF and plasma | LS (n = 139) and NLS (n = 140) | Asthma (n = 17) and healthy subjects (n = 49) | Planar antigen microarray | Sarcoidosis cases have higher reactivity to zinc finger protein 688 and mitochondrial protein L43 |
| Kjellin 2016 (18) | Alveolar macrophages | Sarcoidosis (n = 8) | Control subjects (n = 6) | iTRAQ LC MS/MS | Eighty differentially expressed proteins were identified. There was upregulation of two phagocytotic pathways (Fcγ receptor–mediated phagocytosis and clathrin-mediated endocytosis signaling). Pyruvate metabolism was upregulated in sarcoidosis cases. Oxidative phosphorylation pathway was upregulated in patients with LS and downregulated in patients without LS |
| Martinez-Bravo 2017 (15) | BALF exosomes | Sarcoidosis (n = 15) | Healthy (n = 5) | iTRAQ LC MS/MS on BALF exosomes | Six-hundred and ninety proteins were quantified consistently in exosomes. Proteins more abundant in patients with sarcoidosis are involved in innate and adaptive immune response, protein maturation, and homeostasis. There were indications of downregulation of endocytosis, catabolism (such as peptidase and endopeptidase activity and ubiquitination), and metabolic processes |
Definition of abbreviations: 2DE = two-dimensional electrophoresis; CBD = chronic beryllium disease; DIGE = difference gel electrophoresis; ICAM-1 = intercellular adhesion molecule-1; IPF = idiopathic pulmonary fibrosis; iTRAQ = isobaric tags for relative and absolute quantification; LC = liquid chromatography; LS = Lofgren’s syndrome; MALDI = matrix-assisted laser desorption ionization; MAP = mitogen-actived protein; MS = mass spectrometry; MS/MS = tandem MS; NLS = non–Lofgren’s syndrome; PLCH = pulmonary Langerhans cell histiocytosis; SELDI = surface-enhanced laser desorption ionization; SSc = systemic sclerosis; TOF = time of flight.