Proteomic analysis of plasma from patients with systemic lupus erythematosus: Increased presence of haptoglobin α2 polypeptide chains over the α1 isoforms

Abstract

In the present study plasma samples from 15 systemic lupus erythematosus (SLE) patients and 16 healthy controls of initially unknown haptoglobin (Hp) phenotype were separated by 2-DE, and tryptic digests of the excised Hpalpha polypeptide chain spots were analyzed by MALDI-TOF-MS. Selected tryptic peptides were sequenced by nano-(n)ESI-IT MS/MS. The six major Hp phenotypes were present, although with distinct frequencies in controls and SLE patients. Thus, there were an increased proportion of SLE patients with Hp 2-2, or Hp 2-1S phenotypes. The Hp phenotype distribution resulted in allele frequencies of 0 625 (Hp(2)), 0.281 (Hp(1S)), and 0.093 (Hp(1F)) in healthy controls, correlating fairly well with the allele frequencies of European populations. In contrast, the Hp allele frequencies of the SLE patients were 0.733 (Hp(2)), 0.233 (Hp(1S)), and 0.033 (Hp1(1F)), which clearly indicated an increased frequency of Hp(2), a similar proportion of Hp(1S) and a diminished proportion of Hp(1F) in SLE patients compared with that in healthy controls. Preferential Hpalpha2 expression in SLE patients may contribute to some of the clinical manifestations of the disease such as hypergammaglobulinemia, systemic vasculitis, and cardiovascular disorders.

Lack of Plasma Protein Hemopexin Dampens Mercury-Induced Autoimmune Response in Mice

“…In particular, the latter has been linked to rheumatoid arthritis, juvenile rheumatoid arthritis, and multiple sclerosis. More recently, the haptoglobin ␣2 polypeptide has been found to be over-expressed in the serum of systemic lupus erythematosus patients (7). Haptoglobin is an acute phase plasma protein with high binding affinity for hemoglobin and prevents hemoglobin-derived iron loss.…”

Proteomic analysis of human plasma and peripheral blood mononuclear cells in Systemic Lupus Erythematosus patients

“…From the present literature [33][34][35][36][37][38][39], we note the importance of proteomics, which can help to find new therapeutic targets and it also could help to better understand the cellular mechanisms. …”

“…Hp also has anti-inflammatory effects in autoimmune diseases [92]. The HP22 genotype was shown to be over-represented in inflammatory diseases such as RA, SLE, primary sclerosing cholangitis (PSC) and diabetes mellitus type 2 (T2D) [93,94]. In general, serum levels of Hp increase during inflammatory processes [95] or glucocorticoids admnistration [96].…”

ABIN1 in the pathogenesis of Glomerulonephritis and the novel polocyte-neutrophil proinflammatory axis.

“…The resulting peptides were found to correspond to the 200-239 amino acid portion of the Ro52 protein, supporting the use of autoantibodies against Ro52 as a biomarker. Subsequent studies have supported the role of anti-Ro antibodies (both Ro52 and Ro60) in congenital heart Haptoglobin α2 polypeptide chain differences have been noted between SLE and non-SLE populations via MALDI-TOF-MS [112]. Patients expressing the haptoglobin α2 isoform have been shown to have shorter survival times after coronary artery bypass graft [113] and more severe complications after myocardial infarction [114], possibly due to decreased ability to reduce oxidative stress.…”

“…peptides with SLE flare may offer insight into the cardiac complications seen in SLE and higher levels of haptoglobin α2 have been reported in SLE patients vs. controls [112].…”