Effect of Specific Cleavage of Immunoglobulin G by Plasmin on the Binding and Activation of Plasminogen

Айсина, Р.Б.; Мухаметова, Л.И.; Gershkovich, K.B.; Yakovlev, V. N.; Goufman, Eugene; Tikhonova, N.B.

doi:10.1134/s1068162018010028

Cited by 3 publications

(1 citation statement)

References 22 publications

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“…The heavy chain (PLG-H) and light chain (PLG-L) of PLG were purified from PLG after urokinase cleavage of the peptide bond between amino acids 561–562, followed by a reduction in S–S bonds and acetylation. The separation of PLG-H and PLG-L was performed using Lys-Sepharose 4B, as described elsewhere [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Proteolyzed Variant of IgG with Free C-Terminal Lysine as a Biomarker of Prostate Cancer

Lokshin

Михалева

Goufman

et al. 2021

Biology

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The differential diagnosis of prostate cancer is problematic due to the lack of markers with high diagnostic accuracy. We previously demonstrated the increased binding of IgG to human plasminogen (PLG) in plasma of patients with prostate cancer (PC) compared to healthy controls. Heavy and light chains of PLG (PLG-H and PLG-L) were immobilized on 96-well plates and the binding of IgG to PLG-H and PLG-L was analyzed in serum from 30 prostate cancer (PC) patients, 30 patients with benign prostatic hyperplasia (BPH) and 30 healthy controls using enzyme-linked immunosorbent assay (ELISA). Our results demonstrate that IgG from PC sera bind to PLG-H but not to PLG-L. This interaction occurred through the free IgG C-terminal lysine (Lys) that becomes exposed as a result of IgG conformational changes associated with proteolysis. Circulating levels of modified IgG with exposed C-terminal Lys (IgG-Lys) were significantly higher in PC patients than in healthy controls and in BPH. We used Receiver Operating Characteristic (ROC) analysis to calculate the sensitivity (SN) and specificity (SP) of circulating IgG-Lys for differentiating PC from BPH as 77% and 90%, respectively. The area under the curve (AUC) was 0.87. We demonstrated that the diagnostic accuracy of circulating levels of IgG-Lys is much higher than diagnostic accuracy of total PSA (tPSA).

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Section: Methodsmentioning

confidence: 99%

Proteolyzed Variant of IgG with Free C-Terminal Lysine as a Biomarker of Prostate Cancer

Lokshin

Михалева

Goufman

et al. 2021

Biology

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Increased Blood Concentration of IgG Degradation Products in Prostate Cancer

Goufman

Yakovlev²,

Tikhonova

et al. 2019

Bull Exp Biol Med

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Circulating IgG Fragments for Gastric Cancer and Esophageal Cancer

Goufman,

Tikhonova,

Aleksankin

et al. 2024

Diagnostics

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Blood serum of patients with gastric (n = 68) and esophageal (n = 43) cancer was assessed for proteolytic fragments of IgG. Serum samples of 20 healthy donors were used as a control. We analyzed indicators of hemostasis (prothrombin time, fibrinogen, plasminogen activity, a2-antiplasmin activity, protein C activity) in blood plasma and the level of total IgG in the blood serum. The median IgG-LysK of healthy donors was lower than in esophageal cancer and in patients with gastric cancer. ROC-analysis showed high sensitivity (91%) and specificity (85%) in the group with esophageal cancer but 68% and 85%, respectively, in patients with gastric cancer. Analysis of false negatives IgG-LysK in cancer patients showed that most patients had an advanced stage of cancer accompanied by metastases. Total IgG in the plasma of patients with false-negative IgG-LysK values was 30% lower than in samples with positive values, while the level of a2-antiplasmin was increased and the prothrombin time was shorter. These changes in blood homeostasis may be the reason for an increase in the proportion of false-negative values of the IgG-LysK coefficient. Circulatory IgG-LysK levels increase in the early stages of such cancers as gastric and esophageal cancers. Thus, when used in a panel with other more specific markers for these pathologies, this indicator can significantly increase the early detection of cancer.

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Effect of Specific Cleavage of Immunoglobulin G by Plasmin on the Binding and Activation of Plasminogen

Cited by 3 publications

References 22 publications

Proteolyzed Variant of IgG with Free C-Terminal Lysine as a Biomarker of Prostate Cancer

Proteolyzed Variant of IgG with Free C-Terminal Lysine as a Biomarker of Prostate Cancer

Increased Blood Concentration of IgG Degradation Products in Prostate Cancer

Circulating IgG Fragments for Gastric Cancer and Esophageal Cancer

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