Proteomic analysis of plasma from patients with systemic lupus erythematosus: increased presence of haptoglobin alpha2 polypeptide chains over the alpha1 isoforms.
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.
Departamento de Biología Celular e Inmunología, Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Armilla, Spain.
Esther J
EJ
Pavón
Pilar
P
Muñoz
Antonio
A
Lario
Victoria
V
Longobardo
Montserrat
M
Carrascal
Joaquín
J
Abián
Ana B
AB
Martin
Salvador A
SA
Arias
José-Luis
JL
Callejas-Rubio
Ricardo
R
Sola
Francisco
F
Navarro-Pelayo
Enrique
E
Raya-Alvarez
Norberto
N
Ortego-Centeno
Mercedes
M
Zubiaur
Jaime
J
Sancho
D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015180:Electrophoresis, Gel, Two-Dimensional; D005787:Gene Frequency; D006242:Haptoglobins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics*; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics
D015415:Biomarkers; C485359:HP protein, human; D006242:Haptoglobins; D020033:Protein Isoforms