Quantitative determination of haptoglobin glycoform variants in psoriasis

Abstract

Haptoglobin is an acute phase glycoprotein, secreted by hepatocytes and other types of cells including keratinocytes. Haptoglobin has been suggested to impair the immune response, inhibit gelatinases in the extracellular matrix and promote angiogenesis, but its role in psoriasis is obscure to date. Changes in haptoglobin glycan structure were observed in several diseases. The aim of this study was to investigate whether haptoglobin displays glycan variations in psoriasis. We found that the pattern of plasma haptoglobin glycoforms, following two-dimensional electrophoresis, exhibited significant quantitative differences in spot intensities between patients and controls. Quantitative and qualitative differences in glycan mass, between patients and controls, were found by mass spectrometry of glycopeptides from tryptic digests of protein isolated from both patients and controls. The number of distinct fucosylated glycoforms of peptides NLFLNHSENATAK and MVSHHNLTTGATLINEQWLLTTAK was higher in patients than in controls, but no fucosylated glycan was detected on peptide VVLHPNYSQ-VDIGLIK in either case. The number of peptides with distinct triantennary and tetraantennary glycans was higher in patients than in controls. Abundance or structure of specific glycans, which are present in haptoglobin from patients and are different or missing in normal haptoglobin, might be associated with disease activity.

Protein expression and fucosylated glycans of the serum haptoglobin-β subunit in hepatitis B virus-based liver diseases

“…Our study found that decreased protein expression of serum Hp-b in combination with increased Lewis X-type fucosylation could be a promising diagnostic marker for LC detection. Increase in Hp Lewis X-type fucosylation has been suggested to impair the immune response, inhibit gelatinases in the extracellular matrix, promote angiogenesis, and may give an advantage to the tumor [8]. These findings also suggest that this marker could be employed in a course-monitoring strategy for the clinical management of patients with liver diseases.…”

“…Besides, changes in the Hp glycan structure are observed in several other diseases. Sarrats et al [5] have detected increased levels of Sialyl-Lewis X (SLe(x)) on Hp in chronic pancreatitis, and Maresca et al [8] have found that the level of distinct fucosylated glycoforms is higher in psoriasis patients than in healthy controls.…”

Haptoglobin Function and Regulation in Autoimmune Diseases

“…The structural modification of Hp in psoriasis patients is an abundance or structure change of specific glycans that differ or do not exist in Hp from healthy donors. These changes are associated with altered function of that might have an impact on the disease activity (Maresca et al, 2010). Interestingly, it was found that there is no higher prevalence of any of the three phenotypes of Hp in psoriasis.…”

A Novel Gaussian Extrapolation Approach for 2-D Gel Electrophoresis Saturated Protein Spots

“…2D-GE was performed according to Maresca et al [18], with each sample run in duplicate. For the first-dimension of electrophoresis, 200 lg of plasma protein samples (approximately 3 ll) were applied to 18-cm linear IPG strips 4-7 (GE Healthcare, Uppsala, Sweden) and focused until 72,000 V/h were reached.…”