[Two year investigation of glycosylation profiles in serum IgG from a patient with multiple myeloma].

Although abnormalities of glycosylation profile in serum IgG have been demonstrated in a variety of inflammatory autoimmune diseases such as rheumatoid arthritis, there are only a few reports describing long term monitoring of N-glycosylation profiles in such patients. Here we report the serial finding of N-glycosylation profiles of IgG-kappa M-protein in a patient with multiple myeloma monitored for two years. In this patient, serum formed a gel precipitation upon exposure to air. The HPLC mapping method demonstrated that IgG M-protein in the patient exhibited a significant decrease in the ratio of fucosyl to afucosyl N-glycans compared with that in a healthy control. With remission, the IgG M-protein showed an increase in this ratio, becoming closer to that in the healthy control. However, the gel-precipitation persisted. This finding suggested that this unique property of serum may not be related to the glycosylation profile of the M-protein.

[A case with multiple myeloma in which serum forms gel precipitation upon exposure to air].

We present the case of a 69-years-old man who was admitted to hospital with multiple myeloma. IgG-kappa type monoclonal protein was detected in the serum. When we separated the serum obtained from blood sample of the patient and the lid of the collecting tube was opened, the patient's serum became gelled immediately. When the lid of the collecting tube remained closed, the patient's serum did not become gelled even at 4 degrees C. Moreover, the gelled serum of the patient did not resolve at 56 degrees C. Taken together, these results indicated that gel formation of the patient's serum may not be due to cryoglobulin. It was found that the pH of the patient's serum elevated to pH 8.0 quickly after exposed to air. It was also found that the patient's serum, but not the sera of other IgG-kappa multiple myeloma patients, became gelled as soon as PBS of pH 8.0 was added. These results highly suggest that the patient's serum becomes gelled at pH 8.0. However, the isoelectric focusing of isolated precipitation in the patient showed fractions around the pH 8.5-8.7 zone, which was different from the pH at which the precipitation began to form. We think that this may be the first report of a multiple myeloma patient whose serum becomes gelled after exposed to air.

[Studies on the mechanism of elevation of serum PIVKA-II levels in alcoholic liver cirrhosis].

We measured serum PIVKA-II concentrations in 18 patients with alcoholic liver cirrhosis. Alcoholic liver disease was diagnosed by the history of ethanol intake of more than 900 ml/day for over 10 years. Liver cirrhosis was diagnosed histologically. Infections with hepatitis B and C viruses were ruled out by assaying serum virus markers. No tumor was detected in liver by ultrasonography and computed tomography during observation period. None of the patients studied were positive for alpafetoprotein (AFP). Eight out of 18 (44.4%) patients with alcoholic liver cirrhosis showed elevated serum PIVKA-II levels. In contrast, only eight out of 93 (8.6%) patients with nonalcholic liver cirrhosis had elevated serum PIVKA-II levels. PIVKA-II is well known as a tumor marker of hepatocellular carcinoma (HCC). The rates of positive PIVKA-II found in alcoholic liver cirrhosis approached its rates in HCC. However, the time course for the elevation of serum PIVKA-II levels was different each other in alcoholic liver cirrhosis and HCC. In HCC, serum PIVKA-II "levels" continued to elevate until therapy. In contrast, its elevation was transient and its levels returned to baseline in alcoholic liver cirrhosis. The values of ALT (GPT), gamma-GTP, and ALP correlated poorly with serum PIVKA-II levels in patients with alcoholic liver cirrhosis. To investigate the mechanism by which elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis occurred, we studied the effect of vitamin K on production of PIVKA-II and AFP by hepatocytes. Hepatocytes(Alexander PLC/PRF/F cell line) were cultured in the presence of various concentrations of vitamin K (Kaytwo, Eisai, Tokyo). Vitamin K had no effect on AFP production. In contrast, PIVKA-II production was inhibited by addition of vitamin K in a dose dependent manner. Moreover, elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis was suppressed by administration of vitamin K (Kaytwo) to these patients. Taken together, these results suggest that vitamin K may have a role in the mechanism of PIVKA-II elevation in sera of these patients. Then, we measured serum concentrations of vitamin K(PK, MK-4, MK-7) in these patients. There was no correlation observed between vitamin K and PIVKA-II in these patients. This result suggests that elevation of serum PIVKA-II in these patients may not be due to vitamin K deficiency. One question not answered here is how serum PIVKA-II levels in these patients are suppressed by treatment with vitamin K (Kaytwo). More detailed analysis of the mechanism of elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis is needed.