Autoimmune Pancreatitis Can Transform Into Chronic Features Similar to Advanced Chronic Pancreatitis With Functional Insufficiency Following Severe Calcification.

OBJECTIVES: Because several studies for autoimmune pancreatitis (AIP) have revealed pancreatic calcification resembling that in chronic pancreatitis (CP), we sought to clarify whether AIP could transform into chronic features similar to advanced CP with severe pancreatic dysfunction. METHODS: Pancreatic functions of 92 AIP patients, 47 definite CP patients, and 30 healthy controls were assessed by fecal elastase-1 concentration (FEC), fasting immunoreactive insulin (IRI), and homeostatic model assessment (HOMA)-R. RESULTS: The 92 AIP patients included 17 (18%) with severe calcification (SC) and 75 without. The FEC levels in AIP and CP patients were significantly lower than that in controls. Exocrine insufficiency defined as FEC less than 200 µg/g was 39% in AIP without SC, 56% in AIP with SC, and 74% in CP. Fasting IRI and C-peptide reactivity values in CP were significantly lower than those in AIP, with no significant differences between AIP subgroups. The prevalence of endocrine insufficiency according to fasting IRI less than 5.0 µU/mL was 26% in AIP without SC, 31% in AIP with SC, and 59% in CP, respectively. HOMA-R values were significantly higher in all AIP groups than in CP. CONCLUSIONS: Autoimmune pancreatitis can transform into a state of pancreatic insufficiency after calcification that is less severe than that in definite CP.

[A Case of Secondary Cryofibrinogenemia with Cholangiocarcinoma and Deep Venous Thrombosis].

Cryofibrinogen (CF) is a type of cryoprotein (CP) that can precipitate in cooled plasma but not in serum, and resolves upon warming. We identified a case of secondary cryofibrinogenemia with cholangiocarcinoma and deep venous thrombosis. The patient's cryocrit measured using a Wintrobe tube was 19% in sodium citrate plasma stored for 7 days at 4 degrees C. We performed quantitative analysis of plasma proteins (fibrinogen, IgG, IgA, IgM, C3, C4, α1-antitrypsin, and C-reactive protein) before and after precipitation for 12 hours at 4 degrees C. The plasma fibrinogen concentration decreased by 16.7% (120 mg/dL --> 100 mg/dL), whereas the others were unaffected by precipitation. The CP purified from the patient's plasma was washed three times with saline and subjected to Western blot and Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE) analyses. Western blot analysis indicated that the purified CP was composed of not only fibrinogen but also fibronectin, α1-antitrypsin, α2-macroglobulin, coagulation factor VIII, and IgG, IgA, and IgM. Interestingly, SDS-PAGE analysis showed that the molecular weight of the patient's CF differed from that of purified normal fibrinogen (340 KDa) and consisted of several low-molecular-weight bands (50-250 KDa). From these results, we speculated that CF found in this case was a mixture of degradated fibrinogen and some plasma proteins. In summary, cryofibrinogenemia is a rare and under-recognized disease. Sample information in routine clinical practice is valuable to diagnose this disease.

[Electrophoretic Analysis of Abnormal Data on Serum Protein Electrophoresis].

We recently demonstrated glycation of monoclonal IgA and the presence of IgA-albumin complexes, but the significance of the complexes was not clear. We describe a non-diabetic patient with IgA type M-protein whose serum fructosamine and glycoalbumin levels were elevated. On electrophoresis of the serum protein of the patient, the albumin band shifted to the cathode side. The abnormal precipitin arc of IgA-albumin complexes was detected by immunoelectrophoresis. To elucidate the mechanism of IgA-albumin complexes, we analyzed their properties using immunoelectrophoresis, Western blotting, and two-dimensional gel electrophoresis. The macromolecularized albumin spots were demonstrated by two-dimensional Western blotting with antiserum to human albumin of the patient's serum. Moreover, the IgA-albumin complexes were dissociated on treatment with 2-mercaptoethanol. It can be considered that albumin is bound to the monoclonal IgA molecule by covalent disulfide bonds, and that the albumin binding site is located near the hinge region (311Cys) of the IgA molecule and involves the free SH group, thought to be present in the α-chain.

A sudden onset and the spontaneous remission of severe hypo-high-density lipoprotein cholesterolemia without serious underlying disease: a case report.

BACKGROUND: Severe hypo-high-density lipoprotein (HDL) cholesterolemia is defined by serum values less than 20mg/dl. Few acquired cases, without serious underlying disease, have been reported. CASE: An asymptomatic 75-y-old man was admitted for evaluation of low serum HDL-cholesterol (HDL-C) levels (2-8 mg/dl). The record of periodic medical examinations revealed that a sudden decrease had occurred 5 y ago. Mild anemia and proteinuria were noted but the liver and thyroid function tests were normal. ß-Quantification revealed a relatively low HDL-C (10.8 mg/dl) and the serum lecithin cholesterol acyltransferase (LCAT) activity was low (29.4 nmol/ml/h). Unexpectedly, serum HDL-C levels recovered 2 y after hospital discharge. In addition, the serum LCAT activity, hemoglobin concentrations, and urine protein tests all returned to within the reference interval. Subsequent examinations could not clarify the cause of the sudden onset and spontaneous recovery of the extremely low HDL-C. CONCLUSIONS: We describe an unusual case of acquired HDL-C deficiency in a 75-y-old man that did not have serious pre-existing disease. Recently, extremely low HDL-C levels in patients with the nephrotic syndrome, associated with acquired LCAT deficiency, have been reported. The present case might illustrate a milder form of this disorder, because the clinical findings show many similarities.

Plasma cell leukemia producing monoclonal immunoglobulin E.

A 78-year-old male with lumbar pain and dim consciousness presented the clinical pictures of plasma cell leukemia (PCL) producing a large amount of monoclonal immunoglobulin E (IgE)/kappa protein. Laboratory investigation demonstrated an elevated serum calcium level and renal dysfunction. Systemic bone X-ray survey disclosed only a solitary osteolytic lesion. Circulating plasma cells demonstrated CD19(-)/CD56(-) and MPC-1(-)/CD49e(-)/CD45(+/-), the latter indicating the immature phenotype of the tumor cells. Bone marrow was occupied with immature, atypical plasma cells, of which cytoplasms were positive for IgE by direct immunofluorescence analysis. Chromosomes revealed a translocation of (11;14)(q13;q32), which is concordant with cyclinD1-protein overexpression by immunohistochemistry. He was treated with dexamethasone and vincristine, which somewhat improved the laboratory findings. He died of tumor progression after 4-month admission. The clinical and biological characteristics of IgE-producing PCL, a very rare type of plasma cell dyscrasia, are discussed, reviewing the past literature.

Thyroglobulin mRNA expression in peripheral blood lymphocytes of healthy subjects and patients with thyroid disease.

BACKGROUND: Thyroglobulin (Tg) mRNA is expressed focally in thyroid tissue. In recent years, the Tg gene has been detected in other tissues, including lymphocytes, although the significance of its presence has not been elucidated yet. We measured Tg mRNA expression in the lymphocytes of healthy subjects and those with thyroid disease. METHODS: Analysis of the quantification of Tg mRNA from 20 healthy subjects and 47 subjects with thyroid disease was carried out by real-time PCR. Furthermore, in cultured lymphocytes we compared changes in Tg mRNA expression following stimulation with TSH. RESULTS: Tg mRNA was detected in the lymphocytes of all subjects. Tg mRNA in the lymphocyte sequence matched that derived from thyroid tissue, and mRNA levels were higher in subjects with thyroid disease than in healthy subjects. Following lymphocyte stimulation, Tg mRNA levels were observed to be increased 2.7-fold in Graves' disease and 1.6-fold in chronic thyroiditis compared to healthy subjects. CONCLUSIONS: Tg mRNA in the lymphocytes was quantified by real-time PCR. The levels of Tg mRNA in the TSH-stimulated lymphocytes were noticeably increased in subjects with thyroid disease. These results suggest an interesting relationship between production of Tg antigen in peripheral blood and autoimmunity in thyroid disease.

The clinical utility of Lens culinaris agglutinin-reactive thyroglobulin ratio in serum for distinguishing benign from malignant conditions of the thyroid.

BACKGROUND: Traditionally, the follow-up of differentiated thyroid carcinoma consists of periodic withdrawal from L-T4-suppressive therapy to allow performance of a highly sensitive serum Tg measurement to detect recurrences. We investigated Lens culinaris agglutinin-reactive thyroglobulin ratios in serum to evaluate in usefulness for detection of thyroid carcinoma. METHODS: The study was conducted on 93 serum sample from 23 healthy volunteers, 32 patients with benign thyroid tumor, 28 patients with thyroid carcinoma without metastasis, and 10 patients with thyroid carcinoma with lymph node metastasis. RESULTS: The Lens culinaris Agglutinin reactive thyroglobulin ratio in patients with thyroid carcinoma was significantly lower than in patients with benign thyroid tumor with serum thyroglobulin concentration >200 ng/ml. Among cases of thyroid carcinoma with lymph node metastasis, Lens culinaris Agglutinin reactive thyroglobulin ratios were significantly lower than in patient with thyroid carcinoma without metastasis and those with benign tumor regardless of serum thyroglobulin concentration. CONCLUSION: Measurement of Lens culinaris Agglutinin reactive thyroglobulin ratio in serum may be useful for distinguishing between thyroid carcinoma and benign thyroid tumor.

An immunoglobulin A1 that inhibits lactate dehydrogenase activity, with reversal of inhibition by addition of NADH.

We discovered a patient with low serum lactate dehydrogenase (LD) activity and an abnormal LD isozyme pattern. We analyzed the patient's LD inhibitor using electrophoresis, affinity chromatography, and immunochemical technologies. The LD activity of the patient's serum was inhibited more strongly at 4 degrees C than at 37 degrees C. The decrease of LD activity was more marked in a mixture of the patient's serum with purified LD5 than in that with purified LD1. The immunoglobulin responsible for LD inhibition was an IgA1-lambda. The LD inhibition by the patient's IgA1 was blocked by reduction and alkylation and by NADH. Polymerization of the patient's IgA1 might play an important role in its interaction with LD. Moreover, the possibility exists that part of the patient's IgA1 molecule fits into a pocket of LD in instead of NADH. This is the first report of NADH reversing such LD inhibition.

[Abnormal laboratory data due to interaction between immunoglobulins and other serum proteins].

Two cases with abnormal laboratory data due to interaction between immunoglobulins and other serum proteins are described. Case 1 was a patient with lactate dehydrogenase (LD) -IgG3 complex whose serum LD value was moderately elevated. Case 2 were nondiabetic patients with IgA type M-proteinemia who had significantly increased serum fructosamine (FRA). The IgG3 in Case 1 was found to be conjugated to LD by immunoprecipitation assay. The LD-IgG3 complex was easily dissociated by affinity chromatography on 5'-AMP or Cibacron Blue F3G-A. The relative molecular weights of the patient's gamma3 chains and light chains were 67,000 and 28,000, respectively, by Western blotting, which corresponded to the expected values. However, the patient's IgG3 did not react to the anti-kappa and anti-lambda light chain antibodies in Immunofixation electrophoresis. Serum FRA concentrations were higher in patients (Case 2) with IgA type M-proteinemia or polyclonal hyper-IgA than those with the IgG type or IgM type. The sera from the patients with IgG or IgM type M-proteinemia had FRA only at the position of albumin, but 11 of 13 sera with IgA type M-proteinemia stained for glycoprotein at the position of the M-protein band as well as the albumin band. The abnormal precipitin arcs of IgA-albumin complex were observed in 11 of 13 sera from patients with IgA type M-proteinemia that were glycosylated at the position of M-protein band.