Heterogeneity of antibody specificity in Taiwanese patients with polyneuropathy and IgM paraproteinemia

About half of the Caucasian patients with chronic polyneuropathy and IgM paraproteinemia show serum anti-myelin-associated glycoprotein (MAG) and anti-sulfoglucuronosyl glycosphingolipid (SGGLs) activities. These antibody activities have been demonstrated to react with a carbohydrate epitope known as the HNK-1 or sulfoglucuronic acid (SGA) epitope. However, in Asian populations the occurrence of serum anti-SGA activities has been reported to be relatively rare. We investigated 5 cases of chronic polyneuropathy with IgM paraproteinemia from Taiwan and found that 3 of them had high-titer serum anti-SGA (SGGL/MAG) antibody activities. The clinical symptoms of these 3 patients were consistent with sensory dominant polyneuropathy with a severer involvement of the lower limbs than of the upper limbs. Electromyography and nerve conduction studies revealed severe sensory nerve involvement (no response in 3 cases) and moderate slowing of motor conduction velocity (MCV) without conduction block. The decrease in MCV correlated well with anti-SGA antibody titer (less than 30 m/s with the titration of 1:12,800, normal 55–60 m/s). Pathological findings showed active demyelinating polyneuropathy with myelin ovoid and myelinated fiber loss. Our data suggest that anti-SGGL antibody activities may not be very rare among Asian populations. Additionally, there seems an intriguing possibility that the titer of this antibody correlates with the severity of peripheral nerve involvement in patients of demyelinating polyneuropathy with IgM paraproteinemia.     

Plasmapheresis in paraproteinemia

Indications, results, techniques, laboratory monitoring and complications of therapeutic plasmapheresis in patients with symptomatic paraproteinemia are reviewed. In paraproteinemia associated with severe complications plasma-pheresis has been used successfully as an emergency treatment, as a treatment that reduces temporarily the paraprotein level until reduction of resynthesis is reached by cytotoxic therapy, or as a longterm adjuvant therapy in cases of slowly proliferating plasmacytoma or lymphoma. Plasmapheresis has not been shown to influence the underlying malignant process. Paraprotein-related complications that can be reduced by plasmapheresis are hyperviscosity, hypervolemia, haemorrhagic diathesis, cryoglobulinemic symptoms, rapidly deteriorating renal insufficiency, visual impairment, and neurologic disturbances. Technically, large-pored plasma filters have some advantage as compared to centrifugation techniques. Paraprotein-specific complications of therapeutic plasmapheresis are rare. As an ancillary treatment, therapeutic plasmapheresis has expanded the therapeutic tools in the management of paraproteinemia.     

Trachoma organisms: technical advances in laboratory diagnosis.

New knowledge of the microbiology and immunology of Chlamydia is reviewed. New serological and isolation methods for diagnosis of Trachoma infection are described. Results of studies of ocular and genital Trachoma infection utilizing these new techniques are presented.     

Idiopathic paraproteinemia. III. Increased frequency of paraproteinemia in thymectomized aging C57BL/KaLwRij and CBA/BrARij mice

The influence of thymectomy on the appearance of idiopathic paraproteinemia (IP) during aging was investigated in mice of the C57BL/KaLwRij and the CBA/BrARij strains, which under normal conditions develop IP in high and low frequency, respectively. Compared with sham-thymectomized mice, C57BL mice thymectomized at a young adult age showed a markedly increased frequency and an earlier onset of IP during aging; this was even more pronounced in neonatally thymectomized mice. A similar effect of thymectomy was also observed in mice of the CBA strain. Restriction in the heterogeneity of the serum immunoglobulins and the appearance of transient homogeneous Ig components was another frequent finding and this often preceded the appearance of IP in mice of both strains. Thymectomy did not substantially influence either the incidence of paraproteinemias due to a B cell malignancy or the isotype distribution among the paraproteins produced. The results are compatible with the hypothesis that IP develops in three stages as a consequence of an age-related immunnodeficiency that primarily affects the T immune system.     

Clinicopathologic Characterization of Diffuse-Large-B-Cell Lymphoma with an Associated Serum Monoclonal IgM Component

Recently, diffuse-large-B-cell lymphoma (DLBCL) associated with serum IgM monoclonal component (MC) has been shown to be a very poor prognostic subset although, detailed pathological and molecular data are still lacking. In the present study, the clinicopathological features and survival of IgM-secreting DLBCL were analyzed and compared to non-secreting cases in a series of 151 conventional DLBCL treated with R-CHOP. IgM MC was detected in 19 (12.5%) out of 151 patients at disease onset. In 17 of these cases secretion was likely due to the neoplastic clone, as suggested by the expression of heavy chain IgM protein in the cytoplasm of tumor cells. In IgM-secreting cases immunoblastic features (p<.0001), non-GCB-type (p = .002) stage III-IV(p = .003), ≥2 extra nodal sites (p<.0001), bone-marrow (p = .002), central-nervous-system (CNS) involvement at disease onset or relapse (p<.0001), IPI-score 3–5 (p = .009) and failure to achieve complete remission (p = .005), were significantly more frequent. FISH analyses for BCL2, BCL6 and MYC gene rearrangements detected only two cases harboring BCL2 gene translocation and in one case a concomitant BCL6 gene translocation was also observed. None of the IgM-secreting DLBCL was found to have L265P mutation of MYD88 gene. Thirty-six month event-free (11.8% vs 66.4% p<.0001), progression-free (23.5% vs 75.7%, p<.0001) and overall (47.1% vs 74.8%, p<.0001) survivals were significantly worse in the IgM-secreting group. In multivariate analysis IgM-secreting (p = .005, expB = 0.339, CI = 0.160-0.716) and IPI-score 3–5 (p = .010, expB = 0.274, CI = 0.102–0.737) were the only significant factors for progression-free-survival. Notably, four relapsed patients, who were treated with salvage immmunochemotherapy combined with bortezomib or lenalidomide, achieved lasting remission. Our data suggests that IgM-secreting cases are a distinct subset of DLBCL, originating from activated-B-cells with terminally differentiated features, prevalent extra nodal dissemination and at high risk of CNS involvement.     

A laboratory exercise using a physical model for demonstrating countercurrent heat exchange

A physical model was used in a laboratory exercise to teach students about countercurrent exchange mechanisms. Countercurrent exchange is the transport of heat or chemicals between fluids moving in opposite directions separated by a permeable barrier (such as blood within adjacent blood vessels flowing in opposite directions). Greater exchange of heat or chemicals between the fluids occurs when the flows are in opposite directions (countercurrent) than in the same direction (concurrent). When a vessel loops back on itself, countercurrent exchange can occur between the two arms of the loop, minimizing loss or uptake at the bend of the loop. Comprehension of the physical principles underlying countercurrent exchange helps students to understand how kidneys work and how modifications of a circulatory system can influence the movement of heat or chemicals to promote or minimize exchange and reinforces the concept that heat and chemicals move down their temperature or concentration gradients, respectively. One example of a well-documented countercurrent exchanger is the close arrangement of veins and arteries inside bird legs; therefore, the setup was arranged to mimic blood vessels inside a bird leg, using water flowing inside tubing as a physical proxy for blood flow within blood vessels.     

Gamma-D paraproteinemia - a report of 16 cases.

Paraproteins of the gammaD class are very rare, being found in only 0.3% to 3.0% of the cases of all paraproteinemias. They are difficult to detect and therefore sometimes not found or mis-diagnosed. In the 6500 cases of paraproteinemia we have diagnosed over the last eight years, 16 of them have been gammaD. Consistent with the reports of other gammaD paraproteinemias most of these 16 cases were of type L (13), most patients were male (11), the average age (55), was younger than that of patients suffering from other paraproteinemias, and in all cases the disease followed a rapidly malignant course.     

真菌感染的实验室诊断研究进展

随着易感人群逐渐增多,对临床真菌感染标本的快速检测及真菌培养的分离鉴定日益重要。所幸目前有新的检测方法用来辅助早期诊断及指导经验性的抗真菌治疗。主要的进展集中在对标本的真菌抗原直接检测方面(如半乳甘露聚糖和β-葡聚糖);假丝酵母产色培养基等快速培养鉴定法;微生物生化自动分析系统(VITEK2)和显微扫描(MicroScan)等生化自动检测平板;多肽核苷酸原位杂交,特异性的大范围聚合酶链反应(PCR)检测以及针对临床标本或培养阳性标本直接DNA测序技术。     

布鲁氏菌感染实验室诊断研究进展

布鲁氏菌（Brucella,简称布氏菌）是一种重要的人兽共患病原菌,布鲁氏菌病常发生在牛、羊、猪等家畜中,主要通过接触传播给人类。人类在感染该菌的早期并无特异性症状,其临床表现多样,若不能及时诊断并予以干预,可导致严重关节疼痛和菌血症,甚至引起死亡。布鲁氏菌病一旦广泛发病,不但对畜牧业造成巨大经济损失,还会严重威胁公共安全,因此,布鲁氏菌的快速准确诊断对防治疾病的发展具有重要意义。目前,针对该病原体常见的实验室检测方法包括微生物检测法、免疫学检测法、分子生物学检测法等。本文将就人感染布鲁氏菌的实验室诊断研究进展作以简要综述。     

Lactoperoxidase-catalyzed iodination of human IgM. Differences between 7 S IgM and 19 S IgM and between cell surface 7 S IgM and serum 7 S IgM.

We have studied the lactoperoxidase-catalyzed iodination of human IgM and have measured the ratio of radioactivity incorporated into the mu chain to that incorporated into the L chain (i.e. the mu/L ratio). Both 7 S and 19 S IgM were examined. The ratio of radioactivity was found to be larger for 7 S IgM than for 19 S IgM for all four of the monoclonal IgM proteins examined. The data suggest that some tyrosines of the mu chain which are buried and not available for iodination in 19 S IgM become exposed on conversion of 19 S IgM to 7 S IgM. The mu/L ratio for the IgM found on the cell surface of RPMI 8392 cells was significantly smaller than the ratios for all of the five 7 S IgM proteins studied in solution. It appears, therefore, that a portion of the mu chain of the cell surface IgM of the RPMI 8392 cells is buried in the membrane.     

Basic problems of serological laboratory diagnosis

Serological laboratory diagnosis is inflicted with at least two kinds of basic problems. One type relates to the fact that the serological diagnosis of infectious diseases is double indirect: First, to diagnose an infectious disease, the identification of the microbial agent is sought that caused the disease. Second, to identify this infectious agent, the patient’s immune response to potential agents is measured. So, the serological test is neither measuring directly disease nor the cause of the disease, but the patient’s immune system. Another type of problem is based on the fact that each person’s immune system is very individual. The exact physicochemical properties of antibodies are unique for each clone of antibodies. The way an individual’s immune system sees an infectious agent depends not only on the genetic makeup of the person but also on the personal experience from former encounters with infectious agents. Both types of problems lead to complexities in selecting the appropriate test, in interpreting the results, and in standardizing serological tests. Therefore, a close collaboration of the laboratory with the clinic is mandatory to avoid erroneous conclusions from serological test results, which might lead to wrong decisions in patient care.